Jerold Chun, M.D., Ph.D. (Sanford Burnham Prebys) and

Eric Gershwin, M.D. (UC Davis Health) to Present

January 29, 2018

NON-CONFIDENTIAL

Key Opinion Leader Event: S1P Modulation and Etrasimod - The Next High

Potential Class of Autoimmune Therapies

2

Forward-Looking Statements

This presentation includes forward-looking statements that involve a number of risks and uncertainties, including

statements about our investigative stage drug candidates, including with respect to their potential (including to become

first or best-in-class), preclinical data, safety, efficacy, applications, indications, significance of data, commercialization,

expected data readouts, initiation of new clinical trials, and comparisons to other compounds; our focus, goals, strategy,

plans, timelines and guidance; drug targets, including with respect to potential therapeutic utility; our partnered

programs; financial and other guidance; and other statements that are not historical facts, including statements that may

refer to development plans, differentiation, the market and unmet needs, and statements that may include words such as

“may,” “might,” “will,” “intend,” “plan,” “expect,” “potential,” “possible,” “promise,” “goal” 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: the timing and outcome of research, development and regulatory review

is uncertain; results of clinical trials and nonclinical 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; 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; data and information related to our programs may not

meet regulatory requirements or otherwise be sufficient for further development, regulatory review, partnering or

approval; top-line data may not accurately reflect the complete results of a particular study or trial; analyzing or

comparing data from different clinical trials or nonclinical studies is unreliable and may not result in accurate conclusions

or predictions; other risks related to developing, seeking regulatory approval of and commercializing drugs, including

regulatory, manufacturing, supply and marketing issues and drug availability; we expect to need additional funds to

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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 SEC filings, including under the heading “Risk Factors” in our Quarterly Report on Form 10-Q for the

quarter ended September 30, 2017. We disclaim any intent or obligation to update these forward-looking statements,

other than as may be required under applicable law.

3

Agenda

Amit Munshi, Director, President and CEO, Arena

• Welcome and Company Overview

Dr. Jerold Chun• Sphingosine 1-Phosphate (S1P) Receptors: Validated Drug Targets

Dr. Eric Gershwin• The Broad Potential of S1P Receptor Modulators for the Treatment of Autoimmune

Diseases

Dr. Preston Klassen, EVP, Research & Development and CMO, Arena

• The Promise of Etrasimod: A Potentially Best-in-Class Oral, Next Generation, S1P Receptor Modulator Being Evaluated for Multiple Autoimmune Diseases

Q&A

4

ProgramTherapeutic

Area/IndicationPC Ph 1 Ph 2 Ph 3 Timing

RalinepagPotent IP Receptor Agonist

Pulmonary Arterial

Hypertension (PAH)

Ph 3

Preparations

EtrasimodOptimizedActivityS1P Receptor Modulator

Ulcerative Colitis (UC)Ph 2 Data Q1 2018

Primary Biliary Cholangitis

(PBC)Initiated Ph 2

Pyoderma Gangrenosum

(PG)Initiated Ph 2

APD371Highly Selective Full Agonist to CB2

Pain Associated with Crohn’s

Disease

Ph 2 Data Q1/2 2018

Focus on Pipeline Differentiated Assets with High-Value Potential

5

S1P Receptor Modulators Have Potential Across a Range of Auto-immune Conditions

1. Adapted from targetvalidation.org

S1P is in involved in the pathobiology of numerous disease areas1

84 High Potential Indications Across 12 Immune-Related Therapeutic Areas

Neoplasm

Nervous

system

Immune

systemOther

Endocrine

Reproductive

Digestive

Head

Hematological

Liver

Cardiovascular

Skin

GeneticRespiratory

Eye

Skeletal

ND

HIDP

PD

Auto-

Imm

TC

OSA

EEA

LN

Pso

Der

IBD

CDGA

HNSCC

OSA

EEA

AC

cancercarcino

ma

GA

LNTC

BC

HNSCC

SCC

AC – adenocarcinoma

BC – breast carcinoma

CD – Crohn’s disease

CIDP - chronic inflammatory demyelinating radiculoneuropathy

CPMS – chronic progressive MS

Der – dermatomyositis

EEA – endometrial endometrioidadenocarcinoma

GA – gastric adenocarcinoma

HNSCC – head and neck SCC

IBD – inflammatory bowel disease

LN - lymphoid neoplasm

ND – neurodegenerative disorders

MS – multiple sclerosis

OSA - ovarian serous AC

PD – Parkinson's disease

Pso – psoriasis

RRMS – relapsing-remitting MS

SCC – squamous cell carcinoma

TC – thyroid cancer

UC – Ulcerative colitis

UC

PBC

AIH

CPMS

RRMS

MS

6

Jerold Chun, M.D., Ph.D.Professor & Senior Vice President

Sanford Burnham Prebys (SBP) Medical Discovery Institute

La Jolla, California USAjchun@SBPdiscovery.org

Sphingosine 1-Phosphate (S1P)

Receptors: Validated Drug Targets

Disclosures

Dr. Chun has received honoraria, consulting fees,and/or grant support from:

Abbott, Amira, Arena Pharmaceuticals, Biogen-IDEC,BiolineRX, Celgene, GlaxoSmithKline, InceptionSciences, Johnson and Johnson, Merck, MitsubishiTanabe, Novartis, Ono, Pfizer, Skai Ventures, and Taisho

7

Sphingosine 1-phosphate (S1P) is a phospholipid and sphingolipid

▪Sphingolipids (sphingomyelin) were first discovered in brain extracts by Johann Ludwig Wilhelm Thudichum in 1874

▪Named for their enigmatic “Sphinx-like” nature

▪Sphingosine 1-phosphate (S1P) is a naturally occurring bioactive phospho- & sphingolipid

8

Trends Mol. Med. 12, 65 (2006)

Lysophospholipids (LPs)

9 9

S1P Production

Sphingolipid

metabolism

Ceramide

Sphingosine

S1P

Ceramidases

Sphingosine

kinases

Sphingomyelinases

S1P receptors

OH

N H2

O H

Sphingosine

Inside

S1P

Sphingomyelin

Adapted from 1. Brinkmann and Lynch. Curr Opin Immunol 2002;14:569

S1P transporters (SPNS2 and Mfsd2b)

10

Lysophospholipid receptors

~40% of ALL lipid GPCRs

6 LPA receptors

5 S1P receptors

3 LysoPS receptors (LPS2L only in

mice)

1 LPG/LPI receptor

Most receptors knocked-out in

mice revealing a rich biology

Kihara et al., (2014) Br J Pharmacol 171, 3575-3594 2014

Lysophospholipid receptors

11

Endogenous S1P Signaling Plays an Important Role in a Variety of Physiological Mechanisms

Decreased Inflammation & Improvement in Autoimmune

Disorders

Positive Outcome

Negative OutcomeReduces Immune Cell Migration,Differentiation, & Proliferation

Increased Vasoconstriction, Fibrosis, & Proliferation

S1PR2 S1PR3S1P Receptor Binding S1PR1 S1PR4 S1PR5

Associated With Cardiac, Pulmonary & Possible Tumor-

Related Risks

Potential Disease Implications

• Autoimmunity (e.g. psoriasis,

MS, IBD)

• Neurodegenerative disorders

(Alzheimer’s disease, etc.)

• Inflammation

Potential Disease Implications

• Endothelial dysfunction

• Fibrosis

• Osteoporosis

• Inflammation & fibrosis

• Bradycardia

• Cancer

S1P

12

Species: (Cordyceps) Isaria sinclairii

Phylum: Ascomycota (ascomycetes)

Common Name: Vegetable cicada (nymph)

“Winter worm, Summer grass”

Found: Mixed Forest

Substrate: Ground partly buried

Spores: White

Height: 40 mm

Width: 4 mm

Season: ?

Edible: No

Fungal Photos by Clive Shirely, with permission

New Zealand Encyclopedia

An entomopathogen

13

Fingolimod: Phosphorylation Produces a

Nonselective S1P Receptor AGONIST

fingolimod-P

S1P1 S1P2 S1P3 S1P4 S1P5

(0.3 nM) (3.1 nM) (0.6 nM) (0.3 nM)(>10 M)

Mandala et al. Science 293:346 (2002)

Brinkmann et al., JBC 277:21453 (2002) 14

S1P1 Signaling Regulates Lymphocyte Egress From Lymph Nodes1,2

Blood Efferent lymph

Lymph nodes

S1P1 a GPCR for S1P

S1P1 is a key receptor required for normal lymphocyte egressLymphocyte

S1Pgradient

Normal egress

Lymphocytes egress out of lymph nodes via S1P signaling to circulate between blood and lymphoid tissues

S1P, sphingosine 1-phosphate; S1P1, sphingosine 1-phosphate receptor type 1

1. Brinkmann et al. Am J Transplant 2004;4:1019-25; 2. Schwab and Cyster. Nat Immunol 2007;8:1295-301 15

S1P1 Modulation Selectively Reduces Migration of Lymphocytes From Lymph Nodes

1. Peyrin-Biroulet L, et al. Automimmune Rev. 2017;16:495-503; 2.Olivera P, et al. Gut. 2017;66(2):199-209.

T cells exit lymph nodes

via systemic circulation

T cells move from lymph nodes to

organs/tissues, where they release

cytokines, causing inflammation &

damage

Autoimmune Disease 1

Circulating

T-Lymphocytes

Inflammatory

Cytokines

Target Cell

IFNg

IL23

TNF

IL2

T Cells

Lymph Node

S1P1

S1P Gradient

S1P

S1P Modulator

• Functionally antagonizes S1P1

induces receptor internalization and

degradation disrupting normal lymphocyte

subset egress

• Decrease release of inflammatory cytokines

and reduce organ/tissue damage

• Maintain immune surveillance

Treatment with S1P Receptor Modulator2

Potential Autoimmune Diseases that Might

be Treated with Sphingosine 1-Phosphate

Receptor Modulators

Eric Gershwin, M.D. Distinguished Professor of Medicine, the Jack and Donald

Chia Professor of Medicine, Chief of the Division of Allergy

and Clinical Immunology at the University of California School

of Medicine in Davis

Dr. Gershwin is a consultant to Arena Pharmaceuticals, Bayer, Genentech and Eli Lilly

Disclosures

18

LiverPBC

AIH

PSC

Myasthenia gravis

SLE

Hemolytic anemia

Demyelinating polyneuropathy

Polymyalgia Rheumatica

S1P modulators may

impact treatment of

many autoimmune

diseases

Polymyositis

Sarcoidosis

Psoriatic Arthritis

S1P Modulators May Have Broad Clinical Utility

?

19

A T-cell mediated disease

Pathology is reversible (versus permanent damage)

T cell, Nk cell, T regs and DC contribute to pathology (nearly all AD)

AD with bad treatment options ( i.e. long term steroid use)

The Ideal Target Autoimmune Disease (AD) for S1P

Modulators

20

PBC disease evolves overtime

The immune mechanisms may vary

in individuals

Some newly diagnosed PBC patients

are asymptomatic with maybe

serological markers of AMA+ and/or

elevated Alk\ Phos

Clear need for new treatments

Primary Biliary Cholangitis (PBC)

URSO

21

Intact Bile

Ducts

Cholestasis

Function of Bile Duct (%)

Early Stages of PBC May Be More Receptive to S1P

Modulators

Stage 1+2 maximal T-cell

mediated destruction of bile

ducts

Stage 1 Stage 2

Stage 4Stage 3

S1P

modulators

more

effective?

22

Arrest the progression the disease

Bring about normal Liver Function Test (LFT)

Reduce pruritus and fatigue

Doesn’t add new side effects or risks

Oral delivery

The Ideal Therapeutic?

23

Autoimmune Hepatitis (AIH)

Bile Duct

T cell breakdown in peripheral self-

tolerance, and impaired functions of

FOXP3+ regulatory T cell with effector cell

resistance to suppression at the tissue level

seem to play an important role in AIH

immunopathogenesis

Treatment: steroids and other immune

suppressants

Altered natural killer cell cytokine profile in

type 2 AIH

Epidemiologic data are limited. Among

white adults, the prevalence is estimated to

be 0.1-1.2 cases per 100,000 individuals in

USA (prevalence in Europe is 10X higher)

24

Nearly 40% of AIH Patients Have Other AD

PBCor PSC

autoimmune thyroiditis

vitiligo

RA

Sjogren

UC

conjunctivitis

celiac disease

sle

type I diabetes

MS

polymyalgia

urticaria

others

PBC

or PSC

Most common AD shared with AIH Patients

25

Autoimmune Hepatitis - Treatment Goals

Reduce steroid use - decreasing long term use steroid damage

Increase T regs numbers and improve suppression activity

Reduce T effector cells - less abundant in the liver

Return NK cells to more normal profile

Reduce the number of flares

26

Dermatomyositis

Dermatomyositis includes inflammation,

vasculitis, and perifascicular atrophy. The

predominant inflammatory infiltrate is in the

perimysial region and includes CD4+ T cells

Dermatomyositis affects children and adults

and is the most common inflammatory

myopathy in children

The estimated incidence of dermatomyositis is

9.63 cases per million population - prevalence

between 1/50,000 and 1/10,000

Treatment: dermatomyositis requires the use of

glucocorticoids, topical glucocorticoids, anti-

malarial agents, methotrexate, mycophenolate

mofetil, and/or intravenous immunoglobulin

(IVIg)

27

Polymyositis is a disease caused by

inflammation of the muscles

This occurs when immune cells (clonally

expanded CD8+ T lymphocytes and

macrophages) begin to invade the muscle

tissue

The muscles most severely affected are

typically those closest to the trunk or torso.

This results in weakness that can be severe

The first line treatment for polymyositis is

corticosteroids

The estimated annual incidence has been

reported to be between 1/250,000 and

1/130,000 new cases/year and prevalence

1/14,000

Polymyositis

Polymyositis, like

dermatomyositis, strikes

females with greater

frequency than males

28

Sarcoidosis

Granulomatous inflammation develops

under the regulatory influence of cytokines

produced by local mononuclear

phagocytes, T cells, dendritic cells, and

fibroblasts

Incidence 11 cases per 100,000, prevalence

48/100,000

Blood dendritic cells subsets may migrate

into the affected tissues, contributing to

the formation of the granulomas in

sarcoidosis. It is hypothesized that the

migrating DCs may regulate the T cell

response in sarcoidosis, at least in the

granulomatous lesions

29

Conclusion

S1P modulators biochemical profile makes it well suited to treat many

autoimmune diseases

Over 100 potential T cell mediated autoimmune conditions

Next generation compounds with more favorable risk/benefit profile may

have broader utility across conditions

Additional investigation is needed to explore these compounds in a broad

range of diseases

30

Oral, Next Generation, S1P Receptor Modulator

Optimized Activity Being Evaluated for Multiple

Autoimmune Diseases

Etrasimod

32

Promise of Etrasimod

• Unmet need for safe and effective oral agents addressing a broad range of autoimmune indications

• S1P modulation offers the promise of effective treatment in 80+ conditions

• First-generation pan-S1P modulators (fingolimod - Gilenya) risk-benefit profile limits utility

• Second-generation S1P modulator, ozanimod, is more selective but with potentially sub-optimal pharmacology and pharmacodynamic profile

Unmet Need in Autoimmune Disease

• Optimized pharmacology to avoid off-target activity and ensure broad safety margin

• Pharmacodynamic profile may provide improved risk-benefit

• Potentially supports multiple target patient populations across a broader range of conditions

• Etrasimod

• Ph 2 trial in UC, data Q1’18

• Ph 2 in PG and PBC initiated and ongoing

• Status

Potential Best-in-Class Oral Agent with Broad Clinical Utility

33

Associated with Cardiac, Pulmonary & Possible Tumor-related Risks

Decreased Inflammation & Improvement in Autoimmune Disorders

Positive Outcome Negative Outcome

Dendritic

Cells

Reduces Immune Cell Migration,Differentiation & Proliferation

Increased Vasoconstriction, Fibrosis & Proliferation

T-Lymphocytes Oligodendrocytes

S1PR2 S1PR3

Etrasimod’s Highly Selective S1P Modulation May Avoid Off-Target Activity

No Activity

Receptor Binding

S1PR1 S1PR4 S1PR5

Etrasimod

S1P = sphingosine-1-phosphate; UC = ulcerative colitis. *Data generated at Arena or under sponsored research by Arena.

34

In Contrast with Other S1P Modulators, Etrasimod Does Not Induce S1PR2 Internalization (In Vitro Studies)

S1P Agonists Induce S1PR1 Internalization

(S1PR1 Internalization Assay)

Etrasimod Does Not Induce S1PR2 Internalization

(S1PR2 Internalization Assay)

-12 -11 -10 -9 -8 -7 -6 -5

log [Agonist] (M)

Mean F

luore

scence Inte

nsi

ty

(% D

MSO

tre

ate

d c

ontr

ol)

60

80

90

100

110

70

Etrasimod

Fingolimod

Ozanimod

Amiselimod

-12 -11 -10 -9 -8 -7 -6 -5 -4

log [Agonist] (M)

Mean F

luore

scence Inte

nsi

ty

(% D

MSO

tre

ate

d c

ontr

ol)

40

80

90

100

110

50

60

70

Etrasimod

Fingolimod

Ozanimod

Amiselimod

Arena Data on File; DMSO = dimethylsulfoxide; S1P = sphingosine-1-phosphate

35

Etrasimod First Dose Has Little Impact on Heart Rate Over 24 Hrs – Phase 1 Data

Ozanimod, 1 mg Single Dose (n=18)

Ozanimod, 2 mg Single Dose (n=12)

Placebo (n=9)

Etrasimod, 2 mg, Single Dose (n=10)

Ozanimod1 Etrasimod2

Note – Data Collected from Separate Studies – Cannot be Directly Compared

Sources: 1-Tran JQ et al, J Clin Pharmacol. 2017;57:988-996. 2- ADP334 P1 Data on File

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

10

0

–10

–20

–30

5

–5

–15

–25

Study Hour

Change in M

ean

Hourl

y H

eart

Rate

(bpm

)

10

0

–10

–20

–30

5

–5

–15

–25

Study Hour

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

First dose bradycardia seen with ozanimod led to titration in Ph 2 & 3;

Titration not required in etrasimod Ph 2 clinical study

36

Etrasimod Has a Quick Onset of Action – Phase 1 Data

*After dose escalation of ozanimod (0.3 mg/d on days 1–3; 0.6 mg/d on days 4 and 5; 1 mg/d on days 6 and 7; and 3 mg/d on days 8–10.

Data truncated at day 11 (ozanimod) and 15 (etrasimod) to show on-treatment onset effects Sources: 1-Tran JQ et al, J Clin Pharmacol. 2017;57:988-996. 2- ADP334 P1 Data on File

Note – Data Collected from Separate Studies – Cannot be Directly Compared

Ozanimod1

Etrasimod2

Ozanimod, 2 mg (Dose Escalation*) Placebo

Mean %

Change

from

Base

line

3020100

–10–20–30–40–50–60–70–80

–1 0 1 2 3 4 5 6 7 8 9 10 11Study Day

Study Day

3020100

–10–20–30–40–50–60–70–80

–1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Mean %

Change

from

Base

line

Etrasimod, 2 mg (Fixed Dose) Placebo

• At Day 3, etrasimod showed ~53% lymphocyte reduction

• At Day 3, ozanimod showed ~15% lymphocyte reduction

37

Etrasimod Has a Quick Offset of Action – Phase 1 Data

Sources: 1-Tran JQ et al, J Clin Pharmacol. 2017;57:988-996. 2- ADP334 P1 Data on File;

Ozanimod1

Etrasimod2

Ozanimod, 1 mg (Fixed dose) Placebo

Etrasimod, 2 mg (Fixed Dose) Placebo

Treatment days

• Within 1 week after last dose of etrasimod, lymphocytes returned to within 5% of baseline

• At 2 weeks after last dose of ozanimod, lymphocyte levels still ~40% below baseline

Study Day

30

Mean %

Change

in L

ym

phocyte

Count 20

100

–10–20–30–40–50–60–70–80

1 8 15 22 29 36 43

Study Day

30

Mean %

Change

in L

ym

phocyte

Count 20

100

–10–20–30–40–50–60–70–80

1 5 7 9 15 21 23 28

Note – Data Collected from Separate Studies – Cannot be Directly Compared

38

Optimal Selectivity

Opportunity to be

best-in-class therapy

More Selective

S1P2 internalization

Ozanimod2

(Celgene)

Nonselective

Promiscuous binding can lead to off-

target effects4 & more AEs5

a Elevated LFTs ≥ 3 × upper limit of normal. *Note – Data Collected from Separate Studies – Cannot be Directly Compared

MAD, multiple ascending dose; LFT, liver function test; PFTs, pulmonary function tests.

1. Gilenya® Prescribing Information. Novartis Pharmaceuticals, East Hanover, NJ; 2016. 2. Sandborn WJ, et al. N Engl J Med. 2016;374:1754-1762. 3. Data on File, Arena

Pharmaceuticals. 4. Blaho VA, et al. J Lipid Res. 2014;55:1596–1608. 5. Olivera P, et al. Gut. 2017;66(25):199-209. 6.Kappos L, et al. N Engl J Med 2010;362:387-401.

Newer S1P Receptor Modulators Promise Improved Efficacy and Safety

Etrasimod3

(Arena)Fingolimod1

(Novartis)

First-Generation S1P Receptor Modulator

Second-Generation S1P Receptor Modulator

Rapid lymphocyte lowering &

recovery (2 mg/day)

• Phase 1: ~69%

• Phase 2: TBD

Lymphocyte lowering

(Up to 2 mg/day)

• Phase 1: ~65%

• Phase 2: ~49%

Lymphocyte lowering

(0.5 mg/day)

• Phase 1: ~70%1

• Phase 2 & 3: ~73%6

Safety

No LFT elevationsa

No abnormal PFTs

No titration

No clinically significant first dose

bradycardia

Safety

Elevated LFTsa

Abnormal PFTs

Titration required to blunt

bradycardia

Safety

Elevated LFTsa

Abnormal PFTs

Bradycardia, AV Block

Macular Edema

Carcinoma

Potential Best-in-Class

S1P Receptor Modulator

39

MOA comparison between S1P modulation andJAK inhibition

Untreated Immune System With S1P Receptor Modulator With JAK Inhibitor

Inhibits a specific subset of activated

circulating T- and B-lymphocytes from

migrating to sites of inflammation,

resulting in anti-inflammatory activity, but

with immune surveillance maintained.

Blocks signaling for a large subset of

cytokines and inflammatory pathways in

multiple tissues and cells, resulting in

immunosuppressive activity.

T-cells to

systemic

circulation

T Cells

S1PS1P1Receptor

S1PGradient

Lymph

Node

Circulating

T-Lymphocytes

Inflammatory

Cytokines

Target Cell

T-cells to

systemic

circulation

Lymph

Node

S1P1Receptor

Internalization

Circulating

T-Lymphocytes

(70% reduction)

Reduction in

Inflammatory

Cytokines

Target Cell

S1P1Receptor

Modulator

Broad circulating

immune cells

Inflammatory

Cytokines

Target Cell

Blocked Cytokine

Cell Signalling

B-cells T-cells NK-cells

40

JAKs: Promiscuous Across Cytokine Signaling Receptors

Schwartz DM et al., Nature Reviews Drug Discovery volume 16, pages 843–862 (2017).

41

JAK Inhibitors Represent an Oral MOA, But With Potential Long-Term Safety Issues

Additional safety concerns with marketed and

investigational JAK inhibitors:

✓ VTEs

✓ Gastrointestinal perforations

✓ Herpes Zoster

✓ LDL / Hepatic abnormalities

✓ Anemia

✓ Hyperlipidemia

✓ Liver enzyme elevations

BRAIN

LIVER &

GALLBLADDER

PANCREAS

GASTROINTESTINAL

TRACTKIDNEY &

URINARY TRACT

FEMALE TISSUESMALE TISSUES

JAK/STAT System

• Ubiquitously expressed in multiple body

tissues & cells, i.e. bone marrow, immune

system, muscle tissues, etc.

• Located intracellularly leading to less

selective signaling

LUNG

42

• Enrolled patients with moderate to severe UC (3-component Mayo score of 4-9 that includes endoscopic sub score >2, rectal bleeding score >1)

• Efficacy endpoints include improvement in Mayo Clinical Score (3-component, total), response, remission, mucosal healing versus placebo and dose response

• Safety and tolerability

• 12-week study followed by an open-label extension

Etrasimod Phase 2 Trial in UCEndpoints Include Mayo Score (3-component, total)

Week 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study

12-Week Induction Phase Exit/Transition to Extension Study

12-Week Treatment Period

1 mg q.d. APD334

2 mg q.d. APD334

Placebo

Transition Directly into 36-Week Extension Study (APD334-

005)120 to 160 Patients

Randomized1:1:1

Week 14 Follow-up Safety Visit

Exit/End of Study

~28-Day Screening

Period

Follow-up

43

PBC Has Substantial Unmet Need & Sound Scientific Rationale Exists for Etrasimod

• Primary biliary cholangitis (PBC) is an

autoimmune disease resulting in destruction of

bile ducts, progressive fibrosis & hepatic

failure

• Prevalence ~140-180k (US)

• Unmet Need:

− Up to 50% of patients fail first-line

treatment, UDCA (Ursodeoxycholic acid)

− Significant pruritis; excess doses associated

with liver toxicity & death for second-line

treatment, Ocaliva® (OCA)

− 5-10% of patients undergo liver transplant

• S1P Receptor Modulation Scientific Rationale

− Elevated T cells participate in bile duct

damage, support use of etrasimod

Cholestasis

Liver

Autoimmune Injury by T-Cells

Intrahepatic

Bile Duct

Impaired

Bile Flow

Accumulation of bile acids

Bile Duct Loss

Ductopenia

Fibrosis

Cirrhosis

End-stage disease

Damage to Biliary Epithelial Cells

Etrasimod

UDCA/OCA

44

PBC Patients Often Suffer from Other Autoimmune Disorders, Where Etrasimod May Also Be Beneficial

Neuhauser M et al, Autoimmune Hepatitis – PBC Overlap Syndrome: A Simplified Scoring System May Assist in the Diagnosis. Am J Gastroenterol 2010; 105:345–353; Floreani A et al. Primary Biliary Cirrhosis: Overlaps with Other Autoimmune Disorders. Semin Liver Dis 2014;34:352–360 , Nakamura T et al. Primary biliary cirrhosis (PBC)-CREST overlap syndrome with coexistence of Sjögren's syndrome and thyroid dysfunction. Clin Rheumatol. 2007 Apr;26(4):596-60; Hunter TM et al. Rheumatol Int. 2017 Apr 28; http://www.rightdiagnosis.com/p/polymyalgia_rheumatica/stats-country.htm; https://www.cdc.gov/lupus/facts/detailed.html; Kim HS et al. JAMA Intern Med. 2016;176(11):1716-1717; https://emedicine.medscape.com/article/120937-overview#a5

• ~10% of PBC patients also develop autoimmune hepatitis (AIH) (= ca. 45% of AIH patients)

Significant Unmet Need in PBC-AIH Patients

Indications Overall US

Prevalence

% of

PBC

Liver AIH 32k 45

Rheum Sjögrens 440k 33-100

Endo Hashimoto

Thyroid

3.2Mn 20

Frequent Disease Overlaps in PBC

Etrasimod simultaneously addresses T cell pathogenesis of both diseases, while current

approaches for PBC therapy only focus on reduction of bile acid

45

Etrasimod Emerging as a PotentialBest-in-Class S1P Receptor Modulator

Optimal S1P Receptor Subtype Activity

Excellent Lymphocyte Modulation with Rapid Onset/Offset and No Titration Schedule

Broad

Clinical Potential

Superior

Clinical

Utility

Promise Across a Broad

Range of Autoimmune Conditions

Superior

PK / PD

Potential Best-in-Class

Safety Profile

Selectively Targets S1PR1,4,5

& Avoids S1PR2,3

NASDAQ: ARNA

Thank you