Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): October 4, 2018


Arena Pharmaceuticals, Inc.

(Exact name of Registrant as Specified in Its Charter)






(State or Other Jurisdiction

of Incorporation)

(Commission File Number)

(IRS Employer

Identification No.)




6154 Nancy Ridge Drive,

San Diego, CA



(Address of Principal Executive Offices)


(Zip Code)

Registrant’s Telephone Number, Including Area Code: (858) 453-7200

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)


Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2. below):

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. 






In this report, “Arena Pharmaceuticals,” “Arena,” “Company,” “we,” “us” and “our” refer to Arena Pharmaceuticals, Inc., and/or one or more of our wholly owned subsidiaries, unless the context otherwise provides. Arena Pharmaceuticals® and Arena® are registered service marks of Arena Pharmaceuticals, Inc.

Item 7.01 Regulation FD Disclosure.

Included as Exhibit 99.1 to this Form 8-K is a presentation titled “Arena R&D Day,” dated October 4, 2018, which is incorporated herein by reference. We intend to utilize this presentation and its contents in our R&D Day presentation on October 4, 2018, and in various meetings with securities analysts, investors and others commencing on or after October 4, 2018.

The information contained in Exhibit 99.1 hereto is being “furnished” and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended, is not subject to the liabilities of that section and is not deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, except as shall be expressly set forth by specific reference in such a filing.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.








Arena R&D Day presentation, dated October 4, 2018






Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.


Date: October 4, 2018

Arena Pharmaceuticals, Inc.








/s/ Amit D. Munshi




Amit D. Munshi




President and Chief Executive Officer



Slide 1

ARENA R&D DAY Nasdaq: ARNA October 4, 2018 Exhibit 99.1

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This presentation includes forward-looking statements that involve a number of risks and uncertainties, including statements about the Arena investment thesis, catalysts, value, our investigative stage drug candidates, including with respect to their potential (including to become first or best-in-class), safety, efficacy, indications, significance of data, development plans, differentiation, the market and unmet needs and commercialization, expected data readouts and initiation and progress of new clinical trials; our focus, goals, strategy, plans, timelines and guidance; our partnered programs; financial and other guidance; and other statements that are not historical facts, including statements that may include words such as “may,” “will,” “intend,” “plan,” “expect,” “potential,” “opportunity” 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: 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; 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; the timing and outcome of research, development and regulatory review and feedback is uncertain; unexpected or unfavorable new data; 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; 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. Forward Looking Statements

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Amit D. Munshi President & Chief Executive Officer Preston Klassen, MD, MHS Executive Vice President, R&D and Chief Medical Officer William J. Sandborn, MD UCSD Victor F. Tapson, MD, FCCP, FRCP Cedars-Sinai Presenters and Agenda AGENDA Introductions and corporate overview ~25 min Etrasimod ~30 min + Q&A Ralinepag ~30 min + Q&A Break 10 min Olorinab ~20 min + Q&A APD418 ~15 min Final Q&A Closing

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Arena Management in Attendance John Adams, PhD Vice President, Translational Science Vince Aurentz Executive Vice President, Chief Business Officer Chris Cabell, MD, MHS, FACC Senior Vice President, Clinical Development Kevin Lind Executive Vice President, Chief Financial Officer Suzanne Zoumaras Executive Vice President, Human Resources

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Ralinepag Potent IP Receptor Agonist PAH - Time to Clinical Events Ph 3 Initiated PAH – Ex Capacity 6MWD Ph 3 PAH – Ex Capacity CPET Ph 3 PAH - Differentiation 1H:19 Initiation APD418 Calcium-Independent Myofilament Derepressor Decompensated heart failure (DHF) IND 2019 Deep Pipeline with Therapeutic Focus Program Therapeutic Area/Indication PC Ph 1 Ph 2 Ph 3 Status Etrasimod Optimized Activity S1P Receptor Modulator Ulcerative Colitis (UC) Study 1 Ph 3 Planning Ulcerative Colitis (UC) Study 2 Ph 3 Planning Crohn’s Disease (CD) Ph 2/3 Planning Primary Biliary Cholangitis Ph 2 2H:19 Atopic Dermatitis (AD) Ph 2 Planning Olorinab Highly Selective Full Agonist CB2 Pain Associated with IBD Ph 2 Data Pain Associated with IBS Ph 2 Planning

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Next Stage in Arena Evolution Arena Resets and Builds… 3 Positive Ph 2 Readouts 250%+ Employee Growth Over 24 Mos ~70% of FTEs in R&D (100+ in R&D) 75% New Board 90% New Management 4+ Strategic Deals and Renegotiations ~70% Retail to 85% Institutional Holders

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Next Stage in Arena Evolution 3 Positive Ph 2 Readouts 250%+ Employee Growth Over 24 Mos ~70% of FTEs in R&D (100+ in R&D) 75% New Board 90% New Management 4+ Strategic Deals and Renegotiations ~70% Retail to 85% Institutional Holders Arena Resets and Builds… 4 First- or Best-in-Class Compounds Up to 4 NDAs By 2022/3 7 Phase 3 Trials 4 Phase 2 Trials Preclinical / New Compounds Potential for Regional Partnerships Multiple Catalysts 2019/20 …A Sustainable Company to Deliver Transformational Medicines

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Arena Opportunity Ralinepag Ph 3 PAH - potential $1-2B opportunity Etrasimod Ph 3 IBD (UC & CD) - potential $3-4B opportunity Etrasimod Ph 2 new indications (liver and derm) - potential $1.5-4B opportunity Olorinab Ph 2b IBS/IBD Pain - potential $1-3B opportunity Arena Pipeline Represents $7-13B Commercial Opportunity

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Substantial Catalysts 2019-2022 Etrasimod UC Open Label Data Read-Out Etrasimod UC Ph 3 Initiation Etrasimod CD Ph 2/3 Initiation Etrasimod AD Ph 2 Initiation Etrasimod CD Ph 3 Initiation Etrasimod UC Ph 3 Data Read-Out Etrasimod PBC Ph 2 Readout Etrasimod AD Ph 2 Data Read-Out Etrasimod AD Ph 3 Initiation Etrasimod CD Ph 3 Data Read-Out Olorinab IBD/IBS Pain Ph 2b Initiation Olorinab GI Pain Ph 2 Data Read-out Olorinab GI Pain Ph 3 Initiation Etrasimod UC US NDA Submission 2019 2020 2021 2022 Ralinepag PAH 6MWD Ph 3 Initiation Ralinepag PAH Differentiation Data Read-Out Ralinepag PAH 6MWD / CPET Data Read-Out Ralinepag PAH US Approval / Launch Ralinepag PAH Differentiation Initiation Ralinepag PAH Outcomes Data Read-Out APD418 DHF Ph 2b Data Read-Out Ralinepag PAH CPET Ph 3 Initiation APD418 DHF Ph 1 Initiation Ralinepag PAH US NDA Submission APD418 DHF Ph 2b Initiation APD418 DHF IND Submission APD418 DHF Ph 1 Data Read-Out APD418 DHF Ph 2a Initiation APD418 DHF Ph 2a Data Read-Out GI / HEP / Derm Franchise Cardiopulmonary Franchise

Slide 10

Etrasimod Oral, Next Generation, S1P Receptor Modulator with Optimized Activity Being Evaluated In Multiple Immune-Inflammatory Diseases

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Significant Opportunity to Improve IBD Standard of Care Source: 1UC & CD Disease Landscape & Forecast Reports. DRG. 2018. 2The Facts About IBDs. Crohn’s & Colitis Foundation of America. 2014. 3European Population IBD Prevalence. European Crohn’s and Colitis Organization website viewed Sep 2016. 4Hirten RP, et al. Clin Gastroenterol Hepatol. 2018 Sep;16(9):1374-1384. 5Arena Quantitative Market Research, March 2018. 6Dahlhamer JM, et al. MMWR Morb Mortal Wkly Rep 2016;65:1166–1169. Etrasimod - Next-Generation and Best-in-Class S1P Receptor Modulator ETRASIMOD Best-in-class remission Rapid onset and offset of action No elevated LFTs, abnormal PFTs or macular edema No titration with excellent CV safety Potentially improved barrier function Only 40% of responders achieve remission on most effective biologics at 1 year4 ~60% of IBD patients not receiving SOC (biologics)5 $23B market in 20261 1.6M US Patients2 3.0M EU Patients3 CDC NHIS household survey suggests prevalence may be much higher (3.1M)6

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Source: Arena data on file 100 GI Physicians Quantitative Conjoint Study Shows Etrasimod Emerging as Potential Market Leader Mod/Severe Patients Not Receiving Biologics Etrasimod vs. Ozanimod (Estimated Future Preference) Oral Market Increasing (Estimated Future Preference) S1P vs. JAK (Estimated Preference)

Slide 13

Source: Etrasimod: Post-hoc analysis. Δ=% difference from placebo estimated using Mantel-Haenszel method adjusted with current oral corticosteroid use and prior exposure to TNFα antagonists.. Sources: Ozanimod: Sandborn, et al. NEJM 2016; Xeljanz: Sandborn, et al. NEJM 2017; Entyvio: Feagan, et al. NEJM 2013; Humira: Sandborn, et al. Gastroenterology 2012; Remicade: Rutgeerts, et al. NEJM 2005. TMCS = Total Mayo Clinic Score Etrasimod Demonstrates Competitive Efficacy in UC (4-Domain) Note: No direct head-to-head data available - Caution advised when comparing data across clinical studies Pbo N=121 Pbo N=65 1mg N=67 Pbo N=112 10mg N=429 Pbo N=149 300mg N=225 5mg/kg N=121 Pbo N=246 160/ 80mg N=248 Δ = 10.3% Δ = 10.3% Δ = 11.5% Δ = 7.2% Δ = 23.9% Pbo N=54 2mg N=50 Δ = 18.7% Patients with TMCS ≤ 2 points and No Subscore > 1 point

Slide 14

Proportion of Patients with with Total Mayo Clinic Score ≤ 2 points and No Subscore > 1 point Total MCS = Mayo Clinic Score. Etrasimod: Post-hoc analysis. Δ=% difference from placebo estimated using Mantel-Haenszel method adjusted with current oral corticosteroid use and prior exposure to TNFα antagonists. Ozanimod: Sandborn, et al. NEJM 2016 Etrasimod Remission at 12 Weeks (4-Domain) Pbo N=65 Pbo N=54 1mg N=67 2mg N=50 Pbo N=65 1mg N=67 Δ = 18.7% (p = 0.004) Δ = 10.3% (p = 0.048) Δ = 14.7% (p = 0.01) Etrasimod Ozanimod Note: No direct head-to-head data available - Caution advised when comparing data across clinical studies

Slide 15

S1P = Sphingosine 1-phosphate; UC = ulcerative colitis. *Data generated at Arena or under sponsored research by Arena Arena data on file. Spiegel & Milstien Nat Rev Immunol 2011;11:403-415. Jain & Bhatti Neurology 2012;78:672-689 Etrasimod’s Highly Selective Activity at S1P1,4,5 Reduces Inflammation While Avoiding S1P2,3 Related Side Effects Receptor Subtype Receptor Action Etrasimod Competitive Advantage Positive S1P1 Lymphocyte trafficking Maintained endothelial/epithelial barriers Class leading onset of action Class leading recovery of lymphocyte counts Class leading cardiac safety profile Potential improved mucosal healing S1P4 Regulation of dendritic cell trafficking & activity Potential for additional anti-inflammatory effects S1P5 NK cell trafficking Oligodendrocyte maturation Class effect Negative S1P2 Disrupted endothelial/epithelial barriers Fibrosis Vasoconstriction Proliferation/tumor-related risk Etrasimod has no expected activity at S1P2 Reduced risk for macular edema & pulmonary effects Reduced tumor-related risk S1P3 Increased blood pressure Disrupted endothelial/epithelial barriers Fibrosis Proliferation/tumor-related risk Etrasimod has no expected activity at S1P3 Reduced risk for macular edema, pulmonary effects, and elevated liver enzymes Reduced tumor-related risk

Slide 16

Better mucosal healing Healthier, intact intestinal epithelium reduces migration of microbiota, thus reducing inflammation Enhanced endothelial barrier function potentially reduces side effects, such as macular edema and PFT abnormalities Source: Spiegel S, et al. Nat Rev Immunol. 2011 Jun; 11(6): 403–415. Ungaro et al. Lancet 2017; 389:1756-70. Baumgart & Sandborn Lancet 2012; 380:1590-1605. Jain & Bhatti Neurology 2012;78:672-689. Sanna et al Nat Chem Biol 2006;2:434-441. Arena data on file, ozanimod parent. Etrasimod Pharmacology May Impart Best-in-Class Effects on Barrier Function Enhanced Barrier Function Impaired Barrier Function Intestinal Barrier Dysfunction is a Hallmark of IBD Barrier Dysfunction Leads to Diarrhea, Exacerbated Inflammation and Abnormal Immune Tolerance S1P1 Degradation May Lead to Loss of Protective Signaling * * * * p ≤ 0.01 Tighter Junctions Weaker Junctions S1P1 S1P1 S1P2 Rac Rho Rac

Slide 17

Δ=% difference from placebo estimated using Mantel-Haenszel method adjusted with current oral corticosteroid use and prior exposure to TNFα antagonists. Arena data on file. Advancing to Ph 3 in UC & Crohn’s Disease Ulcerative Colitis (UC) Optimize study design Bigger effect size Expedited trial design Drive rapid enrollment Proprietary methodology for site selection / patient referrals High-touch engagement utilizing internal field based team Crohn’s Disease (CD) Rapid path to Ph 3 Combined Ph 2/3 approach Operational synergies with UC UC Mayo / Disease Activity Index subscore includes: mucosal appearance at endoscopy, rectal bleeding and stool frequency Ph 2 Read-Through to Ph 3 Primary Endpoint in UC Pending feedback from regulatory authorities Δ = 25.6% (p < 0.001) Δ = 9.3% (p = 0.06)

Slide 18

Ph 3 Program in UC Designed for Speed to Market Study 1 Adults Biologics/JAK inhibitor: 50% naïve 50% exposed Etrasimod, 2 mg Placebo Week 12 Week 52 Primary Endpoints Study 1: Week 52 clinical remission (modified Mayo Clinic score) Study 2: Week 12 clinical remission (modified Mayo Clinic score) Potential Secondary Endpoints Endoscopic improvement Steroid-free remission Mucosal healing Study 2 Adults Biologics/JAK inhibitor: 50% naïve 50% exposed Etrasimod, 2 mg Placebo Open-label Extension (OLE) Moderately to Severely Active UC Endpoints Study 3 Long-term, open-label extension Safety and durability of response Pending feedback from regulatory authorities

Slide 19

Ph 3 Program in Crohn’s Disease Designed for Rapid POC & Speed to Market Maintenance Adults Prior Biologics: 50% naïve 50% exposed Week 12 Week 52 Primary Endpoints Remission (symptomatic improvement), and endoscopic remission (co-primary) Potential Secondary Endpoints Improvement in CDAI Induction Adults Prior Biologics: 50% naïve 50% exposed Open-label Extension (OLE) Moderately to Severely Active CD Endpoints Study 4 Long-term, open-label extension Safety and durability of response Etrasimod, 2 mg Placebo Etrasimod, 2 mg Placebo Etrasimod, 2 mg Placebo Interim analysis Responders re-randomized Pending feedback from regulatory authorities

Slide 20

Etrasimod May Have Applications in Broad Range of Diseases Catenion Analysis & Current product development for S1P receptor modulators GI Ulcerative Colitis Crohn’s Disease Liver Primary Biliary Cholangitis Autoimmune Hepatitis Primary Sclerosing Cholangitis Skin Atopic Dermatitis Psoriasis Scleroderma Brain Multiple Sclerosis Lung Asthma Nervous System Amyotrophic Lateral Sclerosis Demyelinating Polyradiculoneuropathy Muscle Polymyositis Bones Rheumatoid Arthritis Psoriatic Arthritis Blood Systemic Lupus Erythematosus 84 High Potential Indications

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Autoimmune disease resulting in destruction of bile ducts, progressive fibrosis & hepatic failure Primary Biliary Cholangitis (PBC) Cholestasis, Ductopenia & Fibrosis Intrahepatic Bile Duct Etrasimod Cirrhosis & End-stage Disease Injury by T Cells Autoimmune Trigger Source: 1Primary Biliary Cholangitis. Disease Landscape & Forecast. DRG. March 2017. 2Primary Biliary Cholangitis. Medscape. Nov 8, 2017. 3FDA approves Ocaliva for rare, chronic liver disease. FDA News Release. May 31, 2016. 4Ocaliva: Boxed Warning Added To Highlight Correct Dosing. FDA Drug Safety Communication. Feb 1, 2018. 5Saffioti F, et al. Cochrane Database Syst Rev. 2017 Mar 28;3:CD011648. Etrasimod Aiming to Address Substantial Unmet Need in PBC 7.5 year survival without treatment & 5-10% undergo liver transplant2 40% inadequate response & 5-10% intolerant to 1L Tx3 Black Box Warning for potential serious injury or death for incorrect dosing of 2L Tx4 No current therapies address underlying autoimmune attack1,5 $2B market in 20261 140K US and EU5 patients1 Significant Need for Treatments that Address Underlying PBC MOD

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Etrasimod Has Potential to Impact Broad Range of Inflammatory Dermatological Diseases DC TH1 TH17 TH2 TH22 Epidermis Lymph Node T T Dermis T cell driven inflammation in multiple immune-mediated skin diseases Etrasimod may improve skin disease by inhibiting dendritic cell & T cell trafficking Etrasimod may improve skin disease by enhancing epithelial healing DC – Dendritic Cells Inflammation, disrupted barriers, skin hyperplasia, fibrosis

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1- Schulze et al. FASEB 2011;25. S1P1 & S1P4 Modulate Dendritic Cell Migration and Cytokine Expression in Skin S1P4-/- mice have exacerbated inflammation in contact hypersenstivity1 DC WT control S1p4-/- control WT FITC S1p4-/- FITC CD8+ CD44+ CD62L- 40 20 0 * 500 250 0 Absolute cell numbers [x103] CD4+ CD44+ CD62L- WT control WT control S1p4-/- control WT FITC S1p4-/- FITC * 45 40 35 30 25 Ear thickness [x10-2 mm] WT control s1p4-/- control WT FITC S1p4-/- FITC * * 0 1 2 DC DC Skin TN TH Lymph Node S1P1 S1P4 TH Migration DC

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Arena data on file. * p < 0.05 compared to vehicle. ** p < 0.0001 compared to vehicle. Mpk = milligram per kilogram Etrasimod Preclinical Data Further Support Dermatologic Indications as Potential Therapeutic Area ** ** ** ** Vehicle Etrasimod 3 mpk * * * Etrasimod reduced collagen deposition and dermal thickening in the bleomycin-induced skin fibrosis model Sham Vehicle 1 mpk 3 mpk 1 mpk Etrasimod FTY720 Bleomycin Sham Vehicle 1 mpk 3 mpk 1 mpk Etrasimod FTY720 Bleomycin Dermis

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Etrasimod’s Clinical Activity in Patients Supports Ongoing Investigation in Skin Disorders Evaluated data on 7 patients with dermatological manifestations 5/6 etrasimod-treated patients showed improvement in DLQI scale - - in either pyoderma gangrenosum (PG) or extraintestinal manifestations (EIM) of IBD 1/1 placebo patient with IBD EIM in Ph 2 study was a non-responder Patient-Level Data “Etrasimod is working very well. Both the patient and I are very happy with the results.” – PI of patient in IBD-EIM Study ” “Very impressed with the patient’s progress. Can the treatment be continued at the study’s completion?” – PI of patient with PG ”

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Etrasimod Early Clinical Result in Pyoderma Gangrenosum Baseline Image Initial Measurement (7/5/17) Current Image Date of Assessment (9/27/17) Initial Area (CmSq) Current Area (CmSq) Percent Area Change Length 4.668 1.520 -67.44% 2.18cm

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Focus on Exploring Atopic Dermatitis Source: 1Atopic Dermatitis/Atopic Eczema. Disease Landscape & Forecast. DRG. August 2018. 2Silverberg, JI. Dermatol Clin. 2017 Jul;35(3):283-289. 3Barbarot S, et al. Allergy. 2018 Jun;73(6):1284-1293. 4Atopic Dermatitis: Survey of 192 Patients. National Eczema Association 2016. 5Egeberg A, et al. J Am Acad Dermatol. 2017 Jan;76(1):98-105. 6Dhingra N, et al. J Invest Dermatol. 2014 Aug;134(8):2071-2074. Severe impact on QoL, including occupational, social & psychological4 8 Year reduction in lifespan5 86% not satisfied with current treatment options4 $24B market in 20261 18M US patients2 22M EU patients3 Atopic Dermatitis (AD) Hallmarks of Disease6 Impaired Skin Epithelial Barriers ® Dendritic Cell Activation ® Local & Systemic T Cell Driven Inflammation Significant Opportunity for Safe and Effective Oral Treatment Option Itch Skin

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Etrasimod Program Timeline 2018-2022 Roadmap 2018 2019 2020 2021 2022 2023 1H 2H 1H 2H 1H 2H 1H 2H 1H 2H Ulcerative Colitis Crohn’s Disease Liver Disease CD: Ph 3 Maintenance CD: Open Label Long-term Extension (OLE) PBC Ph 2 Data Derm AD Ph 2 Interim Analysis Planned Data Legend: Open-label Pending CD: Ph2/3 Induction-1 CD: Ph2/3 Induction-2 NDA Data Data APD334-302: DBI Study APD334-301: Treat-through design Study UC Ph2 OLE (APD334-005) Approval APD334-303: UC Open Label Long-term Extension (OLE) Data Data NDA

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Well characterized, developed in-house Higher selectivity drives efficacy with no off-target activity Improved PD – rapid on-rate + rapid off-rate with true 36 hour half-life UC data supportive of category leading efficacy with good safety / tolerability Moving to Ph 3 in UC, Crohn’s to validate safety and efficacy Moving aggressively in Ph 2 in PBC & AD Ph 3 IBD (UC & CD) - potential $3-4B opportunity Ph 2 new indications - potential $1.5-4B opportunity Etrasimod Progressing Rapidly with Best-in-Class Profile

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Ralinepag Next-Generation, Oral, Selective, Once-Daily Prostacyclin Receptor (IP) Agonist for Pulmonary Arterial Hypertension

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Source: 1Pulmonary Hypertension. Disease Landscape & Forecast. DRG. November 2016. 2Pulmonary Hypertension. DRG. September 2014. 3Coghlan JG, et al. Am J Cardiovasc Drugs. 2018 Feb;18(1):37-47. 4Benza RL, et al. Chest. 2012 Aug;142(2):448-456. 5Burger CD, et al. J Manag Care Spec Pharm. 2018 Mar;24(3):291-302. Arena Quantitative Market Research. Mar. 2018. ERA: Endothelin Receptor Antagonist. PDE5i: Phosphodiesterase-5 Inhibitor Changing the Game - Benefits of IV Prostacyclin in Once-a-Day Oral Therapy RALINEPAG 6.5-10x greater potency vs. selexipag Unprecedented 20.1% PVR improvement with patients primarily on dual therapy 24-hour unremitting receptor engagement Most comprehensive Ph 3 program with differentiated endpoints “If it weren’t for the cumbersome nature of IV epoprostenol, all of my patients with PAH would be on it.” – Hap Farber, MD 50% morbidity and mortality event rate in ERA+PDE-5i treated patients3 7 year median survival4 ONLY 1 in 5 PAH patients receive a prostacyclin5 $6.7B market in 20251 >100K PAH patients worldwide2 Unique Opportunity to Expand the Market

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” ” ” ” Source: 1Burger CD, et al. J Manag Care Spec Pharm. 2018 Mar;24(3):291-302. 2Arena market research, Sept. 2018 Market Research Supports Broad Opportunity and Potential for Ralinepag’s Leading Position Patients on Prostacyclin1 (2015) Oral Prostacyclin Projected Dynamics2 Oral PC Class Growing By… …With Ralinepag Share “The [ralinepag] profile is enough to prefer prescribing over selexipag. That’s not a borderline judgment; my decision would be clear.” – U.S. KOL “This is a winning combination of attributes… what I like best is the peak-to-trough and that this is achieved with only QD dose.” – U.S. Pulm. “The peak-to-trough data suggest [ralinepag] is the closest thing to an oral Flolan.” – U.S. Pulm. “The [ralinepag] product profile has as much efficacy as an IV therapy, but it’s an oral. This will be paradigm shifting.” – U.S. KOL

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Cumulative Survival Epoprostenol Historical Control Month Long Term Source: 1 Barst RJ, et al. N Engl J Med. 1996 Feb 1;334(5):296-301. 2 Sitbon O, et al. J Am Coll Cardiol . 2002 Aug 21;40(4):780-8. Decision Resources 2016. Unremitting Receptor Engagement and Potency Improves Survival In PAH Survival (%) Epoprostenol Conventional Therapy Short Term Week IV Prostacylin Remains Gold Standard Typically Reserved for Late-Stage Patients Chronic IV Catheter = High Rates of Complications Difficult for Patients to Administer and Maintain Proven Survival Benefit with Continuous Prostacyclin IV Infusion

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*PVR, change in least squares mean from placebo; **Flolan: Barst et al NEJM 1996 Feb 1;334(5): 296-301 Ralinepag Impressive PVR Improvement Ralinepag (n=40) Placebo (n=40) Placebo (n=21) -20.1% -21% Flolan® (n=41) 9% -30%** 9.6% -29.8%* Note: No direct head-to-head data available - Caution advised when comparing data across clinical studies Percent Change in PVR Percent Change in PVR IV Flolan ® Naïve Patients Oral Ralinepag 2/3 Patients on Background

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Clear Ph 3 Objectives for a Potential Best-in-Disease Treatment Objective Time-to-Clinical Event Exercise Capacity Time to Market ü ü Breadth of Label ü ü ü Broad Physician Experience ü ü ü Supports use in prevalent patients Supports early use in newly diagnosed patients

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Source: Protocol amendment 1 for: APD811-301, APD811-302, and APD811-304. Trial Assumptions for the ADVANCE Program Design Parameter 301 302 304 Endpoint TtCE Peak V02 (CPET) 6MWD Sample 700 135 290 p <0.01 <0.05 <0.05 Power 90% 90% 90% Hazard Ratio / Treatment Effect HR = 0.6 TE = 1.8 ml O2/Kg/min TE = 25 m Standard Deviation — 3.0 mL O2/Kg/min 65 m

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Ralinepag Program Designed to Differentiate vs. Selexipag Abbreviations: PK, Pharmacokinetic; PD, Pharmacodynamic; XR, Extended Release; PVR, Pulmonary Vascular Resistance; CPET, Cardiopulmonary Exercise Test; MRI, Magnetic Resonance Imaging; 6MWD, 6 minute walk distance; PAH; Pulmonary Arterial Hypertension; PDE5, Phosphodiesterase type 5 inhibitor; ERA, Endothelin Receptor Antagonists; VO2, Peak Oxygen Consumption; QD, quaque die -OR- Once a Day Ph 2 and ADVANCE Ph 3 Studies Differentiation Studies direct comparison to selexipag Cardiac MRI substudy (RV function) CPET Continued impact on PVR and 6MWD in patients on ralinepag out to 2 years POTENTIAL ADVANTAGES DATA SOURCE Once-Daily Dosing Novel Readouts from Ph 3 Long-Term Hemodynamics & Functional Capacity Hemodynamic Advantage

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Hemodynamic data on patients as they switch from selexipag to ralinepag Hypotheses - Compared to selexipag, ralinepag will have improved PVR at both peak and trough Ralinepag Differentiation Study Baseline Measurement Minimum 30 days treatment PVR Subjects enter ralinepag OLE Ralinepag levels for PK analysis PVR Transition subjects to ralinepag Subjects stable on selexipag

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Ralinepag Open-Label Extension (OLE) Study Overview Abbreviations: OLE, Open Label Extension; RHC, Right Heart Catherization; BID, Twice Daily; mg; milligram; FC, Functional Class; 6MWT, 6-Minute Walk Test ~28 Day Screening Period 22-week Treatment Period 9-Week Dose Titration Period 13-Week Treatment Period Transition Period (±3 Week) Stable Dose of Ralinepag (0.01–0.3 mg BID) Placebo Randomized 2:1 R 0 1 2 3 4 5 6 7 8 9 10 14 18 22 25 End of Study Assessments Follow-up OLE BL Open-Label Extension Maintenance Dose of Ralinepag (0.01–0.3 mg BID) Maintenance Dose of Ralinepag (0.01–0.3 mg BID) Initiate/Titrate Ralinepag (0.01–0.3 mg BID) 3 month OLE Visit 6/9/12/35 month OLE Visit RHC RHC Visits every 3 months 6MWT BNP/NT-pro BNP FC 1 RHC

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Ralinepag OLE Baseline Demographics Safety Population – Original (003) Baseline Ralinepag/Ralinepag (N=30) Placebo/Ralinepag (N=15) Age (years) 46 (13) 56 (11) Female/Male (%) 80/20 100/0 PAH Duration (median [range]) 2.5 (0.3-27) 1.8 (0.3-14) PAH Concomitant Medication PDE5i mono 10 (33%) 4 (27%) ERA mono 1 (3%) 4 (27%) ERA + PDE5i / sGCS 19 (63%) 7 (47%) PVR (dyn·s·cm-5) 780 (465) 554 (222) 6MWD (m) 397 (107) 363 (110)

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Ralinepag Demonstrated Long-Term Hemodynamic Improvement D PVR D %PVR -250 -200 -150 -100 -50 0 D P V R ( d y n · s · c m - 5 ) Ralinepag/Ralinepag (N=18) Placebo/Ralinepag (N=11) median 003 Start 007 Start OLE RHC -50 -40 -30 -20 -10 0 D P V R ( % ) Ralinepag/Ralinepag (N=18) Placebo/Ralinepag (N=11) median 003 Start 007 Start OLE RHC

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Ralinepag Demonstrated Sustained Improvement in Exercise Capacity Improvement from Start of Ralinepag Treatment *=p<0.05, **=p<0.01, ***=p<0.001 vs. Original (003) Baseline for Ralinepag/Ralinepag and 007 Baseline for Placebo/Ralinepag At last observation (OLE LOCF): 47% (7/15) PBO/Ralinepag subjects had ≥18 months of exposure 52% (14/27) Ralinepag/Ralinepag subjects had ≥24 months of exposure 0 20 40 60 D 6 M W D ( m ) Ralinepag/Ralinepag (N=27) 12 9 6 Ralinepag Start ** *** * 3 *** ** OLE LOCF Month 0 20 40 60 D 6 M W D ( m ) Placebo/Ralinepag (N=15) 12 9 6 Ralinepag Start * * ** 3 OLE LOCF Month

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Ralinepag OLE Safety and Tolerability Among patients originally randomized to ralinepag in Ph 2 trial, continuation in OLE was associated with a reduced incidence of tolerability events (i.e., headache, jaw pain, etc.) Overall adverse event profile is consistent with the Ph 2 trial and with the underlying disease

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Ralinepag Program Timeline 2018-2022 Roadmap 2018 2019 2020 2021 2022 1H 2H 1H 2H 1H 2H 1H 2H 1H 2H Open Label Extension (APD811-007) and (APD811-303) Ph 3 Program ADVANCE OUTCOMES (APD811-301) ADVANCE CAPACITY (APD811-302) Differentiation Program ADVANCE ENDURANCE (APD811-304) Topline LSLV Topline LSLV Topline LSLV Topline Launch Interim Data Potential Interim Data LSLV DIFFERENTIATION STUDY Potential Interim Data NDA

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Unremitting 24-hour receptor coverage with 6.5-10x potency of selexipag Best-in-Class 20.1% PVR over dual background therapy Ph 3 initiated with most robust program ever developed Additional non-registrational studies to support superiority over selexipag Ralinepag Ph 3 PAH - potential $1-2B opportunity Ralinepag is a Game-Changing Therapy for PAH Patients

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Highly–Selective, Full Cannabinoid 2 Receptor (CB2) Agonist for Gastrointestinal Pain Olorinab

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Olorinab May Address Clear Unmet Need in GI Pain Sources: 1 DRG: IBS Report (2015), 2 IFFGD & UNC: Online Study, n=1,966 (2007), 3 Allergan: Global Impact Report (2018), 4 ZS Analysis (U.S. Census/Datamonitor), 5 CDC: MMWR Prevalence of IBD, n=33,672 (2016), 6 Arena market research, 7 Waljee, Eur J Gastroenterol Hepatol. (2009) Large Patient Populations Major Unmet Needs Customer Insights U.S. Patients (millions)1 IBS-Pain Prevalent Drug Treated 78% of patients report continuous or frequently recurring abdominal pain2 Patient: “I can’t plan anything. End up cancelling due to pain…Sharp pains come out of the blue and make you gasp.” 3 Un-diagnosed IBD-Pain U.S. Patients (thousands)4 Patient: “I would have bouts of cramping so bad that I would roll up on the floor into a ball…” 7 Up to 93% of patients experience pain6 Abdominal Cramps Abdominal Pain Abdominal Cramps Abdominal Pain Diagnosed Treated CDC NHIS household survey suggests the prevalence of IBD is ~3.1 million.5

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Source: 1 DRG: IBS Report (2015), 2The Facts About IBDs. Crohn’s & Colitis Foundation of America. 2014. 3Drossman DA, et al. J Clin Gastroenterol. 2009 Jul; 43(6): 541–550. 4Adelphi 2017. 5Hacker B, et al. P216. Presented at: Crohn’s & Colitis Congress; Jan. 19-20, 2018; Las Vegas, NV. 6Camilleri M, et al. Clin Gastroenterol Hepatol. 2017 Sep;15(9):1338-1349. Olorinab Potential Best-in-Class Profile OLORINAB Non-Opioid 1,000x more selective for CB2 than CB1 Full agonism / no tachyphylaxis Peripherally restricted / no psychotropic effects 78% of IBS patients report frequently recurring/continuous abdominal pain3 90% of IBD patients experience abdominal pain or cramps4 24% of IBD5 and 35% of IBS6 patients taking opiates for pain IBS: 25M patients (US)1 IBD: 1.6M patients (US)2 Significant Unmet Opportunity For Non-Opioid Pain Treatment

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CB2 receptors represent a pathophysiological mechanism in GI tract to regulate abnormal motility, modulate intestinal inflammation & limit visceral sensitivity/pain CB2 Receptor Expression in the GI Tract CB2 receptors located in target tissue, neurons & local immune cells in GI tract CB2 receptor also expressed on visceral afferent nerves During inflammation, enhanced expression on epithelial cells at the ulcer margins & infiltrating immune cells Supporting rationale for inflammatory & non-inflammatory pain signaling The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain Siaˆn I. Jaggar, Fauzia S. Hasnie, Senthy Sellaturay, Andrew S.C. Rice* ; Pain accepted 11 February 1998. Activation of the cannabinoid 2 (CB2) receptor inhibits murine mesenteric afferent nerve activity, Hillsely, Neurogastro Motil (2007) 19, 769–777. Pharmacological Evaluation of a Novel Cannabinoid 2 (CB2) Ligand, PF-03550096, In Vitro and In Vivo by Using a Rat Model of Visceral Hypersensitivity Akira Kikuchi, Pharmacol Sci 106, 219 – 224 (2008)2 Journal of Pharmacological Sciences ©2008 The Japanese Pharmacological Society CB2 Receptors Are Expressed in the Enteric Nervous System

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Castro J, et al. Poster presented at the IASP World Congress on Pain; September 12-16, 2018. ***p<0.001, ****p<0.0001 (comparison to healthy + vehicle); ### p<0.001, #### P<0.0001 (comparison to TNBS + vehicle) Olorinab Demonstrates Strong Pre-Clinical Efficacy in IBD Model * ** *** Olorinab (nM) *p<0.05, **p<0.005, ***p<0.0005 Olorinab decreased activity of visceral pain fibers ex vivo Olorinab decreased visceral pain in response to distension of the colon in vivo Colitis + vehicle (N=18) Healthy + vehicle (N=11) Colitis + Olorinab 30 mg/kg (N=9) Colitis + Olorinab 3 mg/kg (N=8)

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1. Barbara et al., (2014) Curr Opin Gastroenterol 30:352-358;  2. Cremon et al., (2017) Alimentary Pharmacology and Therapeutics 45:909-922; 3. Dr. Lin Chang, unpublished data; 4. Spiller and Major (2016), Nat Rev Gastroenterol Hepatol 13(10):613-21; 5. Vivinus-Nebot et al., (2013) Gut 63:744-752 Shared Mechanisms in IBS and IBD Pain   CB2 receptor IBS symptoms reported in 36% UC and 46% CD patients in apparent remission1,4  Submucosal microinflammation, persisting changes in the lumen and epithelium undetected by conventional testing4,5  Increased CB2 receptor expression on colonic mucosa in patients with IBS2,3   CB2 receptor activation on sensory afferent pain fibers in the colon may reduce visceral hypersensitivity underlying IBS

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Arena data, study being performed by Stuart Brierley's group; Hughes et al., (2009) Gut 58,1333-1341. CVH, Chronic Visceral Hypersensitivity; olorinab given BID (days 24-28) Olorinab Evidences Strong Pre-Clinical Efficacy in IBS Model Vehicle (N=14) Vehicle (N=14) Healthy IBD-like IBS-like Colitis induction 0 28 3 Day Chronic Visceral Hypersensitivity (CVH) to colon distention 7 Complete resolution of inflammation Acute inflammation CVH mice show visceral hypersensitivity after resolution of inflammation Olorinab decreased visceral pain in response to distension of the colon in CVH mice

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Exploratory Objectives Abdominal Pain Score (APS) Patient reported outcome (PRO) C-Reactive Protein (CRP) Average Abdominal Pain Score (AAPS) Patient Health Questionnaire (PHQ)-9 Fecal calprotectin and other biomarkers Weekly or end-of-treatment responders Crohn’s Disease Activity Index (CDAI) PK profiles Olorinab Ph 2a Study in Crohn’s Disease Week 8 Primary Objectives: Safety and tolerability Week 0 Week 10 N = 14 Adults with Crohn’s disease, experiencing abdominal pain – with or without intestinal inflammation 25 mg TID Olorinab (n = 6) 100 mg TID Olorinab (n = 8) Follow-up Visit

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Strong Signal in Average Abdominal Pain Score (AAPS) and Responder Analysis Source: Table 13 AAPS Improvement -4.6 *=p<0.05; **=p<0.01 85% of patients improved at week 4 100% of patients improved at week 8 (Evaluable Population with ≥30% change from baseline in AAPS)

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Successful Ph 2a Study Results Inform Development Path Olorinab trial results demonstrate meaningful efficacy in patients with Crohn’s disease experiencing abdominal pain Reductions in abdominal pain seen within first wk of treatment Statistically significant improvements in pain over 8 wks of treatment 100% of pts with evaluable data exhibited clinical response of >30% change from BL in AAPS (wk 8) Olorinab appeared safe and generally well tolerated in this study No clinically significant changes in heart rate or blood pressure No psychotropic effects No discontinuations due to adverse events Development Plan includes Ph 2b IBS and Ph 2b IBD studies Olorinab in GI Pain - potential $1-3B opportunity

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A First-in-Class Calcium-independent Myofilament Derepressor (CMD) for Decompensated Heart Failure (DHF) APD418

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Source: 1Heart Failure. Disease Landscape & Forecast. DRG. June 2018. 2Dharmarajan K, et al. BMJ. 2015 Feb 5;350:h411. 3Nielsen DV, et al. Anesthesiology. 2014 May;120(5):1098-108. APD418 is First-in-Class for DHF with Novel MOA 70% readmitted within 1 year2 20% increased mortality with each rehospitalization1 No approved treatments proven to improve outcomes3 9.5M AHF hospitalizations in 20251 b3 Receptor APD418 b3 adrenergic receptor (AdrR) antagonist No action on b1/ b2 AdrRs First-in-Class Calcium-independent Myofilament Derepressor (CMD) Long-Awaited Innovative Approach to DHF

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Mebazaa A, et al. Intensive Care med. 2011 Feb;37(2):290-301. Nielsen DV, et al. Anesthesiology. 2014 May;120(5):1098-108. Intensive Care Med (2011) 37:290-301. DOI 10.1007/s00134-010-2073-4 Decompensated Heart Failure Patients Deserve Better and Safer Therapeutic Options Known Issues with Inotropes No improvement in outcomes Increased risk of mortality Decreased efficacy (Dobutamine) Hypotension / arrhythmia liabilities Inotropes typically used in low blood pressure DHF patients Short-term survival by treatment among patients hospitalized with heart failure: the global ALARM-HF registry using propensity scoring methods

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Normal Cardiac Myocyte Cardiac Decompensation Leads to Contractility Repression Normal Contractility b3 b1 / b2 Image adapted from: Kulandavelu S, et al. J Am Coll Cardiol. 2012;59(22):1988-1990. Minimal Repression Decompensated Cardiac Myocyte Decreased Contractility b3 b1 / b2 Strong Repression Agonist Ca++ Ca++ Agonist Increased expression decreased expression

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Calcium-independent Myofilament Derepressor via b3 adrenergic receptor antagonism Improves cardiac contractility with minimal effect on intracellular calcium Avoids inotrope-associated AEs Unique myocyte-specific target to regulate contractility Decompensated Cardiac Myocyte Increased Contractility b3 b1 / b2 APD418 Derepression Agonist APD418 Targeted Therapy for Cardiac Myocyte Dysfunction MOA & Rationale Image adapted from: Kulandavelu S, et al. J Am Coll Cardiol. 2012;59(22):1988-1990. Moniotte S, et al. Circulation. 2001 Mar 27;103(12):1649-55;. Ca++ APD418

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Increased Cardiac Performance Improved Cardiac Function Without Hemodynamic Liability in Animals Supports Advancement Into Clinic Canine model. Arena data on file. Improved Cardiac Safety Cardiac Output (L/min) LV Ejection Fraction (%) Heart Rate (beats/min) Mean Aortic Pressure (mmHg)

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Decompensated heart failure is an area of high unmet medical need with significant morbidity and mortality Current standard of care to improve contractility results in increased long-term mortality (inotropes) APD418 targets a novel mechanism that improves contractility without adverse hemodynamic changes that would put stress on the heart IND filing anticipated Q4 2019 APD418 First-in-Class Novel Therapy for DHF

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Summary 4 First- or Best-in-Class Compounds Up to 4 NDAs By 2022/2023 7 Phase 3 Trials 4 Phase 2 Trials Preclinical / New Compounds Multiple Catalysts 2019/2020 Arena Pipeline Represents $7-13B Commercial Opportunity

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Thank you Nasdaq: ARNA