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2Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Information related to forward-looking statements
This presentation includes forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include statements about the potential of ourcompounds, when, whether and how we expect to continue developing compounds, including lorcaserin, APD125, APD791 and our partnered compounds, upcoming milestones and news, potential drug candidates, the therapeutic potential of GPCRs, our strategy, technologies, preclinical and clinical programs, our ability to identify and develop drugs, future opportunities, potential achievements, goals and expectations, and other statements that are not historical facts, including statements which may be preceded by the words “potential,” “believe,” “expect,” “predict,”“continue,” “likely,” “unlikely,” “anticipate,” “estimate,” “optimistic,” “sustainable,” “intend,” “plan,”“project,” “target,” “aim,” “will,” “may,” “unlikely to be,” and similar words. For such statements, we claim the protection of the Private Securities Litigation Reform Act of 1995. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the time they were made.
Actual results could differ materially from our forward-looking statements due to, among other reasons, preclinical and clinical development is highly uncertain, the success and cost of our research, clinical studies and partnering endeavors, our ability to obtain additional financing, our clinical trials may not proceed at the time we expect or at all, the timing of payments and fees, if any, from our collaborators, and our ability to obtain and defend patents. 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. We disclaim any intent or obligation to update these forward-looking statements, other than as may be required under applicable law.
3Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Focused on discovering, developing & commercializing innovative oral drugs
Lorcaserin for obesityPhase 3 “BLOOM” trial underway
Emerging pipeline of NMEsOral medicines for large, primary care markets
Attractive partnershipsOrtho-McNeil and Merck
Integrated R&D infrastructureFocused on GPCR targets
Multiple expected near-term milestonesDSMB report for lorcaserin
4Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
G Protein-Coupled ReceptorsBroad therapeutic potential
Cell surface receptors that mediate majority of cell-to-cell communication
Hundreds of GPCRs not targeted by current drugs
Selective targeting of specific GPCRs
Maximizes likelihood of intended pharmacology
Minimizes risk of “off target” effects
Validated target class
~40% or more of all drugs target GPCRs
5Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
*Representative of Arena’s research programs.
Program / Indication Phase 3Phase 2Phase 1PreclinicalResearch*
Type 2 diabetes & obesity
Wakefulness promoter
Cardioprotection
Cytokine & immune cell modulators
APD791Thrombosis
MK-0354Undisclosed indication
Merck
LorcaserinObesity
APD125Insomnia
APD668Type 2 Diabetes
Next IND Candidate
Ortho-McNeil
Niacin Receptor Agonists MerckHDL
Pipeline of promising drug candidates
6Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Lorcaserin is a promising oral drug candidate for obesity
BLOOM trial initiated September 2006
Pivotal two-year trial of 3,182 patients
Phase 2 trials of over 800 patients showed:Progressive, meaningful and dose dependent weight lossHigh rate of responseWell-tolerated
References1. Adults 20+over, Center for Disease Control & Prevention, 20062. Estimated annual cost, Center for Disease Control & Prevention, 20023. Deaths in 2000, World Health Organization, 2005
Market Need• More than 30% of Americans are obese1
• Economic cost: $117 billion in the U.S. per year2
• Obesity accounts for +2.6 million deaths worldwide3
7Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Lorcaserin is a novel and selective compound
5-HT2C receptor is a validated target
Located in the hypothalamus
Regulates satiety
May affect metabolic rate
NME that selectively targets the 5-HT2C receptor
~100-fold selectivity over 5-HT2B receptor
~15-fold selectivity over 5-HT2A receptor
Fenfluramine is a non-specific serotonin receptor agonist
Potential to activate all 14 known serotonin receptors
Removed from the market in 1997
8Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
LorcaserinComparison of Lorcaserin and Dexfenfluramine
3011Half Life (hr)
267.7232.2Molecular Weight
2601124
1901000
11
EC-505-HT2A (nM)5-HT2B (nM)5-HT2C (nM)
Dexfenfluramine*Lorcaserin
*The EC-50 data for dexfenfluramine are those of nordexflenfluramine, the active metabolite of dexfenfluramine.
9Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Highly significant weight loss and reduction in BMI and waist+hip circumferenceWell tolerated with no apparent drug effects on heart valves or pulmonary artery pressures; 71% retention rate
Results
Echocardiograms at baseline and end of studyEcho
4 parallel groupsNo diet or exercise advice10 mg, 15 mg & 20 mg daily dose for 12 weeks
Design
469Patients
December 2005Completed
12-Week Trial
Lorcaserin Phase 2b trialDemonstrated significant weight loss
10Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Lorcaserin Phase 2b trialDose-dependent & progressive weight loss
Weight ChangeFrom
Baseline (kg)
15 30 45 60 75 90 105
-4
-3
-2
-1
0
Placebo
Lorcaserin10 mg
Lorcaserin15 mg
Lorcaserin20 mg
***
****
**
**
**
**
**
**
**
**
** **
**
**
*
**
←stop study drug
*p=0.002; **p<0.001mean ± semCompleter subset analysis
Study Day
11Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Lorcaserin Phase 2b trialSignificant number of patients lost ≥ 5% from BL
0
5
10
15
20
25
30
35
% of Patientswith
≥ 5% Weight Loss
Placebo 10 mg 15 mg 20 mg
*p=0.015; **p<0.001Completer subset analysis
**
*
**
12Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Lorcaserin Phase 2b trialHigh response rate & dose-dependent weight loss
-15
-10
-5
0
5
% wtchange
-15
-10
-5
0
5
-15
-10
-5
0
5
-15
-10
-5
0
5
Placebo Lorcaserin 10 mg
Lorcaserin 15 mg Lorcaserin 20 mg
% wtchange
% wtchange
% wtchange
13Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Lorcaserin Phase 2bGenerally well tolerated at doses investigated
Adverse Events (>5% of Patients in Any Group)
3.41.73.45.1Dyspepsia
5.25.12.64.2UTI
5.21.71.70.8Vomiting4.35.94.32.5Fatigue3.44.20.95.9Diarrhea6.01.71.70Dry Mouth6.05.95.18.5Nasopharyngitis3.43.41.79.3URI7.87.66.00Dizziness
11.29.38.53.4Nausea
26.732.229.917.8Headache
20 mg15 mg10 mg PlaceboAdverse Event
14Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Lorcaserin Phase 2b trial No greater FDA valvulopathy incidence in lorcaserin group
Lorcaserin
0.7%2.0%By Treatment
--2.1%--2.0%By Dose
--1 (mild to mild-mod)--
2(1 mild to mod)
(1 mild to mild-mod)Mitral (M) Regurgitation
--1(trace to mild) ----Aortic (A) Regurgitation
20 mg(n=96)
15 mg(n=96)
10 mg(n=99A, 100M)
Placebo(n=99)
FDA valvulopathy (≥ Mild AR; ≥ Moderate MR) rate higher in placebo vs. combined lorcaserin groups
No two-category shifts; One category shifts uniformly distributed
No evidence in preclinical studies of effects on heart valves or pulmonary vasculature after up to 12 months at high doses
15Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Market 2010
Registration plan for lorcaserin
2-year BLOOM Pivotal Phase 3
2009200820072006 2010
Other Phase 3 Studies
1-year Pivotal Phase 3
1-year Pivotal Phase 3
NDA 2009
16Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
APD125A promising oral drug candidate for insomnia
Selective MOA: may lead to fewer side effects
Phase 1: evidence of improved sleep maintenance
Emerging attractive tolerability profile
APD125 to enter Phase 2 trial
References1. Institute of Medicine, 20062. Data Monitor, 2005
Market Need• 50-70 million Americans suffer from a sleep disorder1
• Patients with sleep disorders are at higher risk of health effects1
• Insomnia is a multi-billion market2 despite low awareness about the burden of sleep loss among the general public1
17Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Market Need• 2005 worldwide sales of Plavix totaled $5.9 billion1
• The second best selling drug worldwide1
References1. IMS Health, Inc.
APD791 for arterial thrombosis
Highly selective 5-HT2A receptor inverse agonist inhibits serotonin-mediated thromboembolic processes
Potential to improve therapeutic indexImproved separation of inhibition of thrombosis vs. increased bleeding relative to existing therapies (preclinical data)
Phase 1 start pending completion of preclinical studies
18Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
GDIR agonists are first-in-class therapeutics targeting a novel pancreatic beta cell receptor
Orally active compounds stimulate insulin release without causing hypoglycemia
Activation of GDIR may have both acute and long-lasting beneficial effects on insulin release
Lead compound APD668 in Phase 1
Ortho-McNeil diabetes partnershipGDIR agonists for type 2 diabetes
References1. International Diabetes Federation, 20062. Center for Disease Control and Prevention, 20003. Center for Disease Control and Prevention, 2002
Market Need• Diabetes affects ~200 million people worldwide1
• Diabetes is the sixth-largest cause of death in the U.S.2
• One million new cases of diabetes are diagnosed each year 3
19Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Merck niacin receptor partnershipAgonists for atherosclerosis & other disorders
References
1. American Heart Association
Market Need• Atherosclerosis is implicated in about 3/4 of all deaths from
cardiovascular disease1
• According to AHA, higher HDL is better1
• About 26% of the U.S. population has HDL <40mg/dL1
Three novel GPCR targets for atherosclerosis and other disorders
Targets believed to play role in regulating plasma lipid profiles
Phase 1 trial program generally well tolerated at all doses
$82.5 Million pre-commercial payments plus royalties
20Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Arena finances For the nine months ended Sept. 30, 2006 (in millions)
Total RevenuesExpenses:Research and developmentGeneral and administrativeAmortization of acquired technologyTotal operating expenses
Interest and other income, net
Net loss Allocable to Common Stockholders
Balance Sheet Data:Cash, cash equivalents and short-term investmentsTotal Assets
Total Stockholders’ Equity
$25.9
65.313.2
1.279.7
3.5
$(51.9)
$250.8331.2
$235.3
* Prior 12/31/06 guidance for cash, cash equivalents and short-term investments, plus net proceeds from December 2006 financing $378-385
*
21Arena Pharmaceuticals, Inc. - ARNA - www.arenapharm.com
Expected upcoming events
DSMB month 6 report from BLOOM trial
Initiate APD125 Phase 2 chronic insomnia trial
Initiate APD791 Phase 1 clinical trial
Announce next IND candidate
Announce progress on partnered programs-- Ortho-McNeil and Merck
Obesity
Insomnia
Thrombosis
Partnered
Pipeline