EX-99.1 2 arna-ex991_15.htm EX-99.1 arna-ex991_15.pptx.htm

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Nasdaq: ARNA • October 2020 Atopic Dermatitis Overview Exhibit 99.1

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Forward Looking Statements This presentation includes forward-looking statements that involve a number of risks and uncertainties, including statements about our investigative-stage drug candidate etrasimod, including with respect to its potential (including to become first- or best-in-class), safety, efficacy, indications, mechanism of action, significance of data, development plans, differentiation, the market, opportunity, unmet needs, commercialization, expected data readouts, initiation and progress of clinical trials, and regulatory approval; our focus, goals, strategy, plans, timelines, guidance, and catalysts; and other statements that are not historical facts, including statements that may include words such as “aims to,” “thought to,” “hypothesis,” “may,” “can,” “will,” “likely,” “intend,” “expect,” “opportunity,” “potential,” “up to,” or other similar words. For such statements, we claim the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from expectations, and you are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the time they were made. Factors that could cause actual results to differ materially from such statements include, without limitation: Drug development programs are expensive, time consuming, uncertain and susceptible to change, interruption, delay or termination; the timing and outcome of research, development and regulatory review and feedback is uncertain; we expect to need additional funds to advance all of our programs, and you and others may not agree with the manner in which we allocate our resources; topline data may not accurately reflect the complete results of a particular study or trial; results of clinical trials and other studies are subject to different interpretations and may not be predictive of future results; new data may be unexpected or unfavorable; etrasimod and our drug candidates may not advance in development or be approved for marketing; clinical trials and other studies may not proceed at the time or in the manner expected or at all; enrolling patients in our ongoing and intended clinical trials is competitive and challenging; the duration and severity of the ongoing coronavirus disease (COVID-19) pandemic, including but not limited to the impact on Arena's clinical operations, the operations of Arena's suppliers, partners, collaborators, licensees, and capital markets, which in each case remains uncertain; clinical and nonclinical data is voluminous and detailed, and regulatory agencies may interpret or weigh the importance of data differently and reach different conclusions than Arena or others, request additional information, have additional recommendations or change their guidance or requirements; data and information related to our programs may not meet regulatory requirements or otherwise be sufficient for further development, regulatory review, partnering or approval at all or on our projected timeline; other risks related to developing, seeking regulatory approval of and commercializing drugs, including regulatory, manufacturing, supply and marketing issues and drug availability; Arena's and third parties' intellectual property rights; competition; reimbursement and pricing decisions; risks related to relying on partners and other third parties; and satisfactory resolution of litigation or other disagreements. Additional factors that could cause actual results to differ materially from those stated or implied by our forward-looking statements are disclosed in our Securities and Exchange Commission (SEC) filings, including under the heading “Risk Factors.” We disclaim any intent or obligation to update these forward-looking statements, other than as may be required under applicable law. October 2020 •

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Atopic Dermatitis (AD) October 2020 • Disease State and Pathophysiology

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Etrasimod Aims to Address Unmet Need in Atopic Dermatitis October 2020 • 1. Bieber T. NEJM 2008, 358;14: 1483-1494; 2: Guttman-Yassky et al. JACI 2011; 127(6):1420-1431; 3. Renert-Yuval Y and Guttman-Yassky E. AAAI 2020, 124:28-35 1. 4. Silverberg, JI. Dermatol Clin. 2017 Jul;35(3):283-289.; 5. Barbarot S, et al. Allergy. 2018 Jun;73(6):1284-1293.; 6. Egeberg A, et al. J Am Acad Dermatol. 2017 Jan;76(1):98-105. 7. UC & CD Disease Landscape & Forecast Reports. DRG. 2018 $24B Market Opportunity7 Disease Pathology Heterogeneous inflammatory skin disease, clinically characterized by a chronic rash and itch1,2 Driven by a variety of factors including genetic and environmental factors, a defective skin barrier, and an aberrant immune response1,2 Recruitment of T cells into the skin and their effector functions, including production of Th2 cytokines, are key in the pathogenesis of AD2,3 Severe impact On QoL, including occupational, social & psychological6 Significant Need For simple, safe and effective therapeutics 16.5M US patients4 22M EU patients5

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AD Associated with High Prevalence in Developed Countries and Significantly Impacts Quality of Life (QOL) October 2020 • Children Adults ~16.5 million US adults have a diagnosis of AD (~7.3% of the population). Of those Adults with AD, 40% (6.6 million) reporting moderate-to-severe symptoms1,5 AD is associated with lower overall health rating and life satisfaction, impaired QOL related to mental health, and skin-related QOL in the US population1,6 With an increase in the severity of AD, the risk of cardiovascular death increases by 25%7 Most common form of eczema2 Prevalence in children As high as 20% in industrialized countries2 Continues to increase, and now affecting low income countries as well2,3 Disease severity estimates in the US2,4 ~5.6 million mild ~2.2 million moderate ~.6 million severe AD is associated with worse QOL than several other common chronic illnesses, including heart disease, diabetes and high blood pressure6 1. Chiesa Fuxench ZC, et al. J Invest Dermatol. 2019;139(3):583-590; 2. Silverberg, JI. Dermatol Clin. 2017 Jul;35(3):283-289; 3. Thomsen SF. ISRN Allergy. 2014;2014:354250.; 4. Silverberg JI, et al. Dermatitis. 2014 May-Jun;25(3):107-14.; 5. Asthma and Allergy Foundation of America. Atopic Dermatitis in America. https://www.aafa.org/atopic-dermatitis-in-america/ Accessed September 10, 2020; 6. Silverberg JI, et al. Ann Allergy Asthma Immunol. 2018;121(3):340-347.; 7. Drucker AM, et al. J Allergy Clin Immunol. 2019;143(5):1736-1738.

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Mounting Evidence Points to AD as a Systemic Disorder October 2020 • Higher immune activation recently reported in peripheral blood from AD vs. psoriasis patients: Increased activated T cells1,2  Increase in cytokine-producing T cells1,2 Associated with increased risk for systemic comorbidities:  ...biomarker expression profiles in moderate-to-severe AD patients are clearly different from those in healthy controls, which confirms the presence of systemic inflammation in AD patients and supports the hypothesis that AD is a systemic disorder.6 —Thijs JL, et al.  Asthma4,6 Rhinitis6 Eosinophilic GI Conditions6 Cardiovascular Disease3 IBD5 SLE7 Obesity8 Asthma Rhinitis Cardiovascular Disease IBD SLE Obesity 1. Czarnowicki T, et al. J Allergy Clin Immunol. 2015;136(1):208-211.; 2.Ungar B, et al. J Invest Dermatol. 2017;137(3):603-613.; 3. Brunner PM, et al. J Invest Dermatol. 2017;137(1):18-25.; 4. Ravnborg N, et al. J Am Acad Dermatol. 2020;S0190-9622(20)30299-1.; 5. Lee H, et al. J Am Acad Dermatol. 2020;S0190-9622(20)31006-9.; 6. Thijs JL, et al. J Allergy Clin Immunol. 2018;141(4):1523-1526. 7. Andersen YM, et al. J Am Acad Dermatol. 2017;76(2):274-280.e1. 8. Silverberg JI, et al. Br J Dermatol. 2012;166(3):498-504.

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Overlapping Disease Biology In UC, Psoriasis and AD Compelling Clinical Data Generated in UC and PsO With S1P1 Modulators October 2020 • 1. Sandborn WJ, et al. Gastroenterology. 2020;158(3):550-561. ; 2. Ungaro R, et al. Lancet. 2017;389(10080):1756-1770. ; 3. Lowes MA, et al. Annu Rev Immunol. 2014;32:227-255. ; 4. Vaclavkova A, et al. Lancet. 2014;384(9959):2036-2045. ; 5. Hassan Z, et al. Cureus. 2020;12(8):e9901. Ulcerative Colitis Psoriasis Atopic Dermatitis Cytokine Dysregulation Th2, Th1, Th172 Th1 and Th173 Th2, Th1, Th22, Th175 Evidence for role of S1P1 Modulation Etrasimod: Phase 2b OASIS1 Etrasimod 2mg: 3-Domain Mayo Δ = 25.6% (p < 0.001 versus placebo) Ponesimod: Phase 2 Psoriasis4 Ponesimod 20 mg, 46% PASI 75 (p<0.0001 versus placebo) Ponesimod 40 mg, 48.1% PASI 75 (p<0.0001 versus placebo) Etrasimod: Phase 2b ADVISE TBD

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Recently Published Systematic Review and Meta-Analysis Reveals Bidirectional Association Between AD and IBD October 2020 • Lee H, et al. J Am Acad Dermatol. 2020;S0190-9622(20)31006-9. Subgroup meta-analyses of Ulcerative Colitis (UC) and Crohn’s Disease (CD) showed that UC has a bidirectional association with AD1: podds of AD in UC (OR 1.23; 95% CI 1.11-1.35) podds of UC in AD (OR 1.53; 95% CI 1.07-2.18) Image Source: Lee H, et al. J Am Acad Dermatol. 2020;S0190-9622(20)31006-9.

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AD is a Heterogenous Biphasic Disease Mediated by Broad Range of Cytokines Acute FlareChronic State October 2020 • Cytokine milieu in AD thought to be influenced by multiple factors1: Stage of disease Ethnicity Age Klonowska J, et al. Int J Mol Sci. 2018;19(10):3086. Image Source: Leung DY, Guttman-Yassky E. J All ergy Clin Immunol. 2014;134(4):769-779

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During an Acute Flare, Staphylococcus aureus Exploits Epidermal Barrier Defects in AD to Trigger Cytokine Expression1,2,3 1. Nakatsuji T, et al. J Invest Dermatol. 2016;136(11):2192-2200. ; 2. Leung DY, Guttman-Yassky E. J Allergy Clin Immunol. 2014;134(4):769-779.; 3. Kim J, Kim BE, Leung DYM. Allergy Asthma Proc. 2019 Mar 1;40(2):84-92.; 4. Igawa S, et al. J Invest Dermatol. 2019;139(8):1743-1752.e5 October 2020 • S1P1 knock-down in human keratinocytes reduced S. aureus-induced cytokine production4 S1P1 is Expressed in Human Skin Keratinocytes and Upregulated by Staphylococcus Aureus4 Image Source: Leung DY, Guttman-Yassky E. J Allergy Clin Immunol. 2014;134(4):769-779. Image Source: Igawa S, et al. J Invest Dermatol. 2019;139(8):1743-1752.e5.

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Etrasimod Reduced Trafficking of Dendritic Cells From Skin to Lymph Node and Reduced T Cell Activation in Lymph Nodes in Pre-Clinical AD Model 1. Crosby C, et al. Poster Presented at Revolutionizing Atopic Dermatitis virtual Symposium; April 2020. Poster #159. October 2020 • Data in Mice Lymph Nodes1 Langerin+ Denditic Cells Acute Flare 1 2 Etrasimod Etrasimod Langerin- Denditic Cells Activated Cells T Cells ** *** **** *** **** **** **** **** **** **** **** **** Sham Vehicle Dexamethasone 1mg/kg Etrasimod 1mg/kg Etrasimod 3mg/kg 2×104 2×104 1×104 5×103 0 1×105 8×104 6×104 4×104 2×104 0 8×106 6×106 4×106 2×106 0 2×106 1×106 5×105 0 Image Source: Leung DY, Guttman-Yassky E. J Allergy Clin Immunol. 2014;134(4):769-779.

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Etrasimod Led to Fewer T Cells, B Cells, and Eosinophils Which are Thought to be Mediators of Inflammation in Atopic Dermatitis October 2020 • 1. Crosby C, et al. Poster Presented at Revolutionizing Atopic Dermatitis virtual Symposium; April 2020. Poster #159 3 Acute Flare: Th2 Inflammation Chronic Disease State: Heterogeneous Th1/Th2/Th17 Inflammation 3 Etrasimod Etrasimod 2 Etrasimod Etrasimod Lowered Circulating T Cells, B Cells and Eosinophils in Pre-Clinical Models of AD1 B Cells Eosinophils Sham Vehicle Dexamethasone 1mg/kg Etrasimod 1mg/kg Etrasimod 3mg/kg *** **** **** ns ** **** * **** ** 3×104 2×104 1×104 0 6×103 4×103 2×103 0 1.5×105 1×105 5×104 0 T Cells Image Source: Leung DY, Guttman-Yassky E. J Allergy Clin Immunol. 2014;134(4):769-779.

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3 Acute Flare: Th2 Inflammation Chronic Disease State: Heterogeneous Th1/Th2/Th17 Inflammation Reduced Trafficking of T Cells Correlated with Decreased Tissue Th2, Th1 and Th17 Cytokines Relevant to Acute Flare and Chronic Disease State 1. Crosby C, et al. Poster Presented at Revolutionizing Atopic Dermatitis virtual Symposium; April 2020. Poster #159 October 2020 • 3 Etrasimod Etrasimod Etrasimod Reduction in Th2 and Th1 Cytokines in Pre-Clinical Models1 IFNγ TNFα IL-6 Sham Vehicle Etrasimod 1mg/kg Etrasimod 3mg/kg pg Analyte/mg Protein pg Analyte/mg Protein pg Analyte/mg Protein pg Analyte/mg Protein ns * ** *** ns ** * * IL-4 Image Source: Leung DY, Guttman-Yassky E. J Allergy Clin Immunol. 2014;134(4):769-779.

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In Addition to Th2 T cells, Th1, Th22 and Th17 are Significant Mediators of Disease in the Chronic Phase October 2020 • 1. Zhou L, et al. J Allergy Clin Immunol. 2019;144(1):144-156. ; 2. Renert-Yuval Y, Guttman-Yassky E. Ann Allergy Asthma Immunol. 2020;124(1):28-35. AD is characterized by activation of more than just the Th2 immune pathway With increased disease chronicity among adults, there are gradual increases with increasing age in markers of Th1/Th17 pathways1 Therefore, treatments inhibiting several immune pathways may provide therapeutic benefit in a broader population of patients For new treatments to address the unique fingerprint of each AD subtype, targeting of other immune axes beyond IL-4/IL-13 is needed. It likely will be necessary to target a combination of cytokines to fully control AD, regardless of disease phenotype” —Yael Renert-Yuval, MD ; Emma Guttman-Yassky, MD, PhD2 Chronic Disease State

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Based on Pre-Clinical Data, Upstream Mechanism of Etrasimod May Interrupt Multiple Pathways that Mediate Acute Flare and Chronic AD October 2020 • 1. Crosby C, et al. Poster Presented at Revolutionizing Atopic Dermatitis virtual Symposium; April 2020. Poster #159 3 Acute Flare: Th2 Inflammation Chronic Disease State: Heterogeneous Th1/Th2/Th17 Inflammation 3 Etrasimod Etrasimod 2 1 4 Etrasimod Targeted Mechanism of Etrasimod: Disruption of Immune Cell Trafficking1 Reduced trafficking of dendritic cells from skin to lymph node à reduced activation of T cells in LN Reduced circulating lymphocytes à fewer immune cells available to traffic to the skin, including T cells, B cells, and eosinophils Downstream Functional Outcomes1 By broadly limiting T cell trafficking, both Th2 and Th1 tissue cytokines were decreased, including IL-4 and IFNγ Etrasimod overall improved disease outcome: Decreased inflammation and lowered histological score 3 2 1 4 Image Source: Leung DY, Guttman-Yassky E. J Allergy Clin Immunol. 2014;134(4):769-779.

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October 2020 • Definitions: DC, dendritic cell; IL, interleukin; MOA, mechanism of action; Th, T helper cell; S1P, sphingosine-1-phosphate *Statements are aspirational in nature and not intended to be based on direct evidence at this stage in the program Etrasimod MOA May Address Mediators of Acute Flare and Chronic Phases of Atopic Dermatitis Broader mechanism with potential to impact the Th2 pathway and beyond Patients in the chronic state of AD can have elevations in Th1, Th2, and Th17 inflammation, thus warranting a broader approach than biologics that impact single pathways Etrasimod has shown favorable results in a Phase 2 clinical trial of another Th2-mediated disease, ulcerative colitis Etrasimod has potential to affect the trafficking of DCs and Th subsets, resulting in reductions in multiple cytokines, which may be beneficial across clinical endotypes Potential to improve skin barrier By reducing inflammation and Th2 cytokines, etrasimod has potential to improve skin barrier defects S1P1 and S1P5 are expressed in skin keratinocytes, and research studies are ongoing to investigate the potential of etrasimod to modulate keratinocyte functions directly Potential to improve itch By reducing inflammation, etrasimod has potential to lessen itch symptoms Research and clinical studies are ongoing to investigate the potential of etrasimod to modulate itch signaling

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Market Opportunity October 2020 •

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October 2020 • Abbreviations: CAGR, compound annual growth rate; DRG, Dieringer Research Group (marketing research group); IL, interleukin; JAK, janus kinase; PDE4, phosphodiesterase 4 1. Source: DRG AD Disease Landscape & Forecast 2019’ *Note: based on SCORAD (children aged 0-14), PO-SCORAD (patients aged 15+); 2. Spherix Q2 2020 DRG Projects Multiple New Product Entrants to Grow AD Market to $24B by 20281 Novel therapies will increase drug treatment rates AD market is expected to grow in all 7 major markets at CAGR of 27% AD Market Size Sales (USD, millions) AD Market Share (2018) g JP g EU5 g US $2.1B $24.2B AD Market Share (2028)

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0%50%100% Safety and Simplicity Heavily Influence Dermatologists’ Treatment Decisions October 2020 • http://www.pmlive.com/pharma_news/amgen_raises_forecasts_after_closing_$13.4bn_otezla_deal_1317936#:~:text=Otezla%20is%20the%20leader%20in,as%20AbbVie's%20Humira%20(adalimumab). Otezla. Package insert. Amgen, Inc. June 2020. ; Enbrel. Package insert. Amgen, Inc. August 2020. ; Humira. Package Insert. Abbvie, Inc. March 2020. ; Stelara. Package insert. Janssen Pharmaceuticals, Inc. July 2020. ; Cosentyx. Package insert. Novartis. June 2020. ; Skyrizi. Package insert. Abbvie, Inc. March 2020.; OAmgen raises forecasts after closing $13.4bn Otezla deal; 43 63 65 79 82 Enbrel Stelara Humira Cosentyx Skyrizi Drug Safety/Side Effects Simplicity Efficacy (PASI-75) Market Leader Otezla GI side effects Oral 28% Humira Boxed Warning: Infection / Cancer Injectable 65% Stelara Risk of Infection / Cancer Injectable 66% PsO PASI-75 Response 28 Otezla

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Dermatologists’ JAK Safety Perceptions are Shaping Their View of the Class and Future Intended Use October 2020 • Abbreviations: RA, rheumatoid arthritis; JAK, janus kinase Source: Spherix AD Q2 2020 Survey questions: Although these risk factors have not been witnessed in clinical trials for AD, in your opinion, how transferable will these risk factors be to the AD population? (n=100); If Rinvoq™ and other oral JAK inhibitors have a similar label warning label for AD, how will this impact your use of the products if approved? (n=100) gNo/low transferability to the AD population (1-3) gModerate transferability to the AD population (4-7) gExtremely transferable to the AD population (8-10) Transferability of JAK Safety Data Warning Label Impact on Prescribing Oral JAKs How transferable will these risk factors be to the AD population? Rate the warning label impact on prescribing of oral JAKs gNo/low impact on my willingness to prescribe oral JAKs in AD once approved (1-3) gModerate impact on my willingness to prescribe oral JAKs in AD once approved (4-7) gLarge negative impact on my willingness to prescribe oral JAKs in AD once approved (8-10) 7.2 7.1 7.0

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In 2017, Dupilumab was First Advanced Line Agent Approved for AD in ~15 years October 2020 • Adults 12-17Y 6-11Y <6Y Prevalence 8,200 2,500 2,500 2,400 Moderate-to-severe 2,600 800 700 700 Biologics eligible 1,700 400 90 75 74 8 Approved 2022e Share of Biologics eligible 4.4% 2.0% U.S. AD population by age group1 (in thousands, approximate) Dupilumab came to market with an EASI improvement of 35% and no significant safety warnings/boxed warning Despite 3+ years of market exclusivity, dupilumab has penetrated <5% of the adult AD opportunity Biologic, injection therapy and access are barriers to broader dupilumab uptake (HCP and patient) 1. Truven Payer Claims Data; IQVIA Sanofi Custom SOB Report; Data on file (Sanofi Dupixent IR Event June 11, 2020)

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In the US High-Dose JAK Agents Have Encountered Regulatory Challenges with Both Product Approvals and Product Labeling October 2020 • Sources: https://www.biopharmadive.com/news/fda-boxed-warning-for-abbvies-jak-inhibitor-clouds-gileads/561186/ (Aug 16, 2019 ;https://www.ema.europa.eu/en/news/ema-confirms-xeljanz-be-used-caution-patients-high-risk-blood-clots (Nov 15, 2019); https://www.globenewswire.com/news-release/2020/05/20/2036672/0/en/GILEAD-AND-GALAPAGOS-ANNOUNCE-POSITIVE-TOPLINE-RESULTS-OF-PHASE-2B-3-TRIAL-OF-FILGOTINIB-IN-MODERATELY-TO-SEVERELY-ACTIVE-ULCERATIVE-COLITIS.html https://www.fiercebiotech.com/biotech/fda-rejects-gilead-s-would-be-blockbuster-filgotinib-over-toxicity-concerns (Aug 19, 2020); 2019 2020 Q1 Q3 Q4 Q2 Q3 08/16/19 Upadacitinib approved in RA with JAK boxed warning and high-dose 30MG not submitted based on >VTE 11/15/19 CHMP (EMA) concludes UC maintenance dose of 10mg bid not recommended in patients at high risk of blood clots 1/17/20 Baricitinib is filed for AD in EU but not in the US 5/20/20 Filgotinib Ph 2b/3 UC study 200mg achieves modest results 8/19/20 Filgotinib RA submission rejected by FDA, safety concerns keying on MANTA data

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October 2020 • 1. Renert-Yuval Y, Guttman-Yassky E. Ann Allergy Asthma Immunol. 2020;124(1):28-35. For new treatments to address the unique fingerprint of each AD subtype, targeting of other immune axes beyond IL-4/IL-13 is needed. It likely will be necessary to target a combination of cytokines to fully control AD, regardless of disease phenotype.1 —Y. Renert-Yuval, MD et al

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Competitive Landscape October 2020 •

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ADVISE Ph 2b Trial – 12 Week Efficacy Period Followed by 52 Week Open-Label Extension Open-label (52 weeks) Overall trial duration of 76 weeks Day 1 Week 16 Screening Period 12-Week Treatment Period Follow-up Period Week 12 4-Week Wash out < 4 Weeks Baseline EASI Week 68 Week 72 4-Week Follow-up October 2020 • 12 Week efficacy vs. other Ph 2 AD trials 16 Week Etrasimod 2 mg Etrasimod 1 mg Placebo Etrasimod – selected dose R

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Cross-Trial Comparison Suggest Disease Duration and Baseline Severity May Influence Treatment Effect (Ph 2 Trials) October 2020 • Abbreviations: AD, atopic dermatitis; AE, adverse event; BSA, body surface area; EASI, Eczema and Severity Index; IGA, Investigator Global Assessment Scale for AD; NRS, numerical rating scale; PBO, placebo; QW, once a week, Q2W, once every two weeks; QD, once daily 1. Thaçi,D The Lancet, Vol 387 January 2, 2016 2.Guttman-Yassky, E J AM ACAD DERMATOL 2019 VOLUME 80, NUMBER 4 3. Gooderham, M JAMA Dermatol. 2019;155(12):1371-1379. 4. Guttman-Yassky, E J ALLERGY CLIN IMMUNOLMARCH 2020; 5. Guttman-Yassky,E JAMA Dermatol. 2020;156(4):411-420. doi:10.1001/jamadermatol.2020.0079 Dupilumab1 Baricitinib2 Abrocitinib3 Upadacitinib4 Lebrikizumab5 Trial Overview Ph 2 Trial Design Mono vs. PBO N=379; 16 weeks 300mg Q2W, Q4W Bari + TCS vs. PBO + TCS N=124; 16 weeks 4mg, 2mg, QD Mono vs. PBO N=267; 12 weeks 200mg, 100mg, QD Mono vs. PBO N=167; 16 weeks 30mg, 15mg, QD Mono vs. PBO N=280; 16 weeks 250mg Q2W, Q4W Age, mean 39, 37, 37 33, 42, 35* 39, 41, 43 40, 39, 40 39, 40, 42 Baseline Duration of AD 31, 27, 30 22, 26, 18* 20, 24, 26* 24, 23, 27 22, 23, 24 IGA (4), n (%) 47%, 43%, 48% NA 37%, 47%, 38% 26%, 55%, 44% 29%, 33%, 39% BSA 53%, 51%, 51% NA 48%, 49%, 48% 42%, 51%, 46% 39%, 41%, 47% EASI, mean 34, 29, 33 20, 22, 22* 25, 27, 25 28, 31, 33 26, 26, 29 Efficacy IGA (0/1) 30%, 22%, 2% 21%, 22%, 8% 44%, 30%, 6% 50%, 31%, 2% 45%, 34%, 15% Efficacy Mean EASI % ∆ 68%, 64%, 18% 65%, 64%, 46% 83%, 59%, 35% 74%, 62%, 23% 72%, 69%, 41% EASI-50 78%, 71%, 30% 61%, 57%, 37% 79%, 56%, 27% NA 81%, 77%, 46% EASI-75 52%, 49%, 11% 34%, 30%, 20% 65%, 41%, 15% 69%, 52%, 10% 61%, 56%, 24% Note: No direct head-to-head data available; Caution advised when comparing data across clinical trials *Median

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EASI-75 Peak Response: Dupilumab and Upadacitinib Patients Stop Improving Between Weeks 8-12 October 2020 • 1. Thaçi D, et al. J Dermatol Sci. 2019;94(2):266-275. ; 2. Guttman-Yassky E, et al. J Allergy Clin Immunol. 2020;145(3):877–884. Mean (± SE) EASI over time1 Mean (± SE) % Improvement From Baseline in EASI (LOCF)2 Upadacitinib: Placebo-corrected Δ diminishes from week 8 to week 16 across all doses Imputed no. of patients 0 wks 1 wk 2 wks 4 wks 6 wks 8 wks 12 wks 16 wks Placebo (n=460) 1 18 69 129 173 210 241 258 300 mg q2w (n=457) 0 9 24 36 50 60 70 87 300 mg qw (n=462) 0 13 21 45 59 71 95 119 š g p n Week Visit (Weeks) * * * * * * * * * * * * * + + Placebo Upadacitinib 7.5 mg QD Upadacitinib 15 mg QD Upadacitinib 30 mg QD š p n Placebo Dupilumab 300 mg q2w Dupilumab 300 mg qw

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Atopic Dermatitis Ph 2b Trials Percent Change EASI from Baseline at Week 12 October 2020 • 1. Wollenberg A, et al. J Allergy Clin Immunol. 2019;143(1):135-141. ; 2. Guttman-Yassky E, et al. JAMA Dermatol. 2020;156(4):411‐420. ; 3. Thaçi D, et al. Lancet. 2016;387(10013):40‐52. ; 4. Gooderham MJ, et al.  JAMA Dermatol. 2019;155(12):1371‐1379. ; 5. Guttman-Yassky E, et al. J Am Acad Dermatol. 2019;80(4):913‐921. ; 6. Guttman-Yassky E, et al. J Allergy Clin Immunol. 2020;145(3):877‐884.6 Placebo Adjusted EASI % Improvement from Baseline Note: No direct head-to-head data available; Caution advised when comparing data across clinical trials Potential for commercial viability tralokinumab1 lebrikizumab2 dupilumab3 abrocitinib4 baricitinib5 upadacitinib

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Placebo Adjusted EASI 75 Improvement from Baseline Atopic Dermatitis Ph 2b Competitive Landscape at Week 12 October 2020 • Note: No direct head-to-head data available; Caution advised when comparing data across clinical trials tralokinumab1 Lebrikizumab2 dupilumab3 abrocitinib4 baricitinib5 upadacitinib6 1. Wollenberg A, et al. J Allergy Clin Immunol. 2019;143(1):135-141. ; 2. Guttman-Yassky E, et al. JAMA Dermatol. 2020;156(4):411‐420. ; 3. Thaçi D, et al. Lancet. 2016;387(10013):40‐52. ; 4. Gooderham MJ, et al.  JAMA Dermatol. 2019;155(12):1371‐1379. ; 5. Guttman-Yassky E, et al. J Am Acad Dermatol. 2019;80(4):913‐921. ; 6. Guttman-Yassky E, et al. J Allergy Clin Immunol. 2020;145(3):877‐884.6

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Placebo Adjusted IGA 0/1 Improvement from Baseline Across Atopic Dermatitis Ph 2b Competitive Landscape at Week 12* October 2020 • *dupilumab values reflect Week 16 results, as Week 12 results are not available in the public domain Note: No direct head-to-head data available; Caution advised when comparing data across clinical trials tralokinumab1 lebrikizumab2 dupilumab3 abrocitinib4 baricitinib5 upadacitinib6 1. Wollenberg A, et al. J Allergy Clin Immunol. 2019;143(1):135-141. ; 2. Guttman-Yassky E, et al. JAMA Dermatol. 2020;156(4):411‐420. ; 3. Thaçi D, et al. Lancet. 2016;387(10013):40‐52. ; 4. Gooderham MJ, et al.  JAMA Dermatol. 2019;155(12):1371‐1379. ; 5. Guttman-Yassky E, et al. J Am Acad Dermatol. 2019;80(4):913‐921. ; 6. Guttman-Yassky E, et al. J Allergy Clin Immunol. 2020;145(3):877‐884.6

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Etrasimod Potential Best-in-Class S1P Receptor Modulator with Opportunity for Broad Applicability 1. Sandborn WJ, et al. Gastroenterology. 2020;158(3):550-561. ; 2. Vermeire S, et al. Poster Presented at United European Gastroenterology Week (UEGW); October 2019. Poster #P0403 October 2020 • Receptor Pharmacology1,2 Highly specific S1P1,4,5  No evidence of off-target activity / deleterious barrier function due to S1P2,3 Pharmacodynamics1 Rapid On-Rate (treating flare) Rapid Off-Rate (infection control) Control1,2 Strong durable remission rates observed, generally well tolerated safety with no titration No elevated LFTs, abnormal PFTs, macular edema Convenience Oral, once-daily Minimal monitoring expected No titration Etrasimod Intrinsic Design Features

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Nasdaq: ARNA