Please see page 5 for rating definitions, important disclosures

and required analyst certifications

All estimates/forecasts are as of 05/08/14 unless otherwise stated.
Wells Fargo Securities, LLC does and seeks to do business with companies
covered in its research reports. As a result, investors should be aware that
the firm may have a conflict of interest that could affect the objectivity of the
report and investors should consider this report as only a single factor in
making their investment decision.



May 8, 2014

Equi ty Resear ch
Orexigen Therapeutics, Inc.
OREX: Q1--2014 Set Up to Be A Transformational Year

Summary: After the May 8 market close, Orexigen reported in-line financial
results for Q1 highlighted by continuing pre-market preparations by U.S. partner
Takeda for the launch of NB32 with its 900-person field force following FDAs
potential approval around the June 10 PDUFA date, while Orexigen continued to
work towards completion of its responses to the CHMPs 120-Day Questions for
the European Marketing Authorization Application. 2014 could become a
transformational year for the company with FDA approval in obesity in June, a
strong launch by Takeda soon thereafter, potential EU approval sometime in H2,
completion of an ex-U.S. partnership for obesity and Type 2 Diabetes post-EU
approval, and potential initiation of a Phase III T2DM program by the end of
2014. We probability weight U.S. approval around the PDUFA data at 90%. Over
the long term, we believe OREX is undervalued based on its T2DM strategy and
the potential to be the 1
st
obesity agent to demonstrate a superiority outcome on
Major Adverse Cardiovascular Events (e.g., mortality). Based on our recent work
with U.S. private payers, we believe an NB32 label with a T2DM claim and
superiority on MACE outcomes has the potential to meaningfully improve
reimbursement coverage compared to other obesity drugs. Based on changes to
our model, our 2014E GAAP EPS decreases to $0.13 from $0.14.
Partnering interest in NB32 ex-U.S. appears to have increased since
late 2013. While specific details were not provided on the call, OREX noted that
the positive interim LIGHT CV risk analysis and the recently announced life-cycle
management strategy for a T2DM label have generated increased interest in ex-
U.S. partnering discussions for NB32. This is not surprising to us as currently
only one drug is approved in Europe for the treatment of obesity, and NB32 is
becoming a clinically de-risked asset, in our view, based on the LIGHT study
analysis -- especially due to cardiovascular risk. Recall in the Ph. III, 56-week
COR-DM study, NB32 resulted in -0.5% (modified intent-to-treat) and -0.7%
(excluding rescue medicines) placebo-adjusted HbA1c, and weight loss of 11.6
pounds (ITT analysis) and 13.5 pounds (completers analysis) in obese diabetics (a
historically tougher to treat population than obese non-diabetics).
NB32 MAA Update. OREX plans to file its answers to the CHMPs 120-Day
questions in late May and expects a CHMP decision or the 180-Day list of
questions in Q3 (late July). If CHMP issues 180-Day questions (a possibility due
to potential new questions on the LIGHT data -- which will be included in
OREXs answers to the 120-Day questions), OREX believes it can address these
within 30 calendar days (file in late August). A CHMP decision would then pace a
final European Commission decision 60 to 90 days later (by the end of 2014).
Financials: OREX reported EPS of -$0.23 vs. our -$0.21. Based on achievement
of regulatory and sales milestones later in Q2 associated with the U.S. NB32
approval ($100M), we expect OREX to end 2014 with ~$300M in cash.

Valuation Range: $11.00 to $12.00
We value OREX based on a blend of a 5-5.5x P/S multiple applied to 2020E
revenues of $568M and a DCF using a 10% discount rate. Key risks are clinical and
regulatory failures of NB32 in obesity and T2DM, obesity competition, and poor
U.S. reimbursement.

Investment Thesis:
We believe OREX is undervalued based on NB32 in Type 2 diabetes and obesity.

Outperform / V


Sector: Biotechnology
Market Weight


Earni ngs Reported
2013A 2014E 2015E
EPS Curr. Prior Curr. Prior
Q1 (Mar.) ($0.21) ($0.23) A (0.21) NE
Q2 (June) (0.19) 0.48 0.47 NE
Q3 (Sep.) (0.19) (0.11) NC NE
Q4 (Dec.) (0.21) (0.11) NC NE
FY ($0.81) $0.13 0.14 ($0.04) NC
CY ($0.81) $0.13 ($0.04)
FY P/E NM 40.8x NM
Rev.(MM) $3 $109 $73
Source: Company Data, Wells Fargo Securities, LLC estimates, and Reuters
NA = Not Available, NC = No Change, NE = No Estimate, NM = Not Meaningful
V = Volatile, = Company is on the Priority Stock List

Due to use of diluted vs. basic shares in calculation of 1/4
EPS, the sum of the four 1/4's does not equal FY 2014 EPS.


Ticker OREX

Price (05/08/2014) $5.30

52-Week Range: $4-8

Shares Outstanding: (MM) 111.5

Market Cap.: (MM) $591.0

S&P 500: 1,875.63

Avg. Daily Vol.: 2,279,630

Dividend/Yield: $0.00/0.0%

LT Debt: (MM) $115.0

LT Debt/Total Cap.: 20.0%

ROE: NM

3-5 Yr. Est. Growth Rate: NE

CY 2014 Est. P/E-to-Growth: NM

Last Reporting Date: 05/08/2014

After Close

Source: Company Data, Wells Fargo Securities, LLC estimates, and Reuters




Matthew J. Andrews, Associate Analyst
(617) 603-4218 /
matt hew. j . andrews@wel l sf argo. com
Brian Abrahams, M.D., Senior Analyst
(212) 214-8060 /
bri an. abrahams@wel l sfargo. com
Shin Kang, Ph.D., Associate Analyst
(212) 214-5036 /
shi n. kang@wel l sfargo. com

WELLS FARGO SECURITIES, LLC
Biotechnology EQUITY RESEARCH DEPARTMENT


2

Company Description:
Orexigen Therapeutics, Inc. (La Jolla, California) is a biopharmaceutical company focused on developing novel
products for the treatment of obesity and Type 2 diabetes mellitus (T2DM). Orexigen's portfolio is highlighted
by NB32 (Contrave), its novel anti-obesity therapy which combines sustained release formulations of
naltrexone and bupropion. NB32 has completed four Phase III studies and successfully met an interim safety
analysis in late 2013 for its ongoing Phase III cardiovascular outcomes study (LIGHT). Beyond obesity,
Orexigen and North American partner Takeda are planning to develop NB32 for the treatment of T2DM. The
T2DM strategy may enable Orexigen and Takeda to differentiate NB32 from other anti-obesity agents and
could allow for better reimbursement with U.S. health plans, a major headwind for any novel anti-obesity
therapy. NB32's PDUFA date is June 10, 2014, and its European Marketing Authorization Application is
currently under review by the CHMP. Behind NB32, Orexigen has a second novel anti-obesity agent, Empatic,
a combination of bupropion and zonisamide, which has completed Phase II studies. Orexigen will not advance
Empatic into Phase III without a partner.

Exhibit 1. Upcoming Milestone Chart
Agent Timing Event
Q2 (End of May)
2014
Orexigen files responses to CHMP's 120-Day Questions.
June 10, 2014 U.S. PDUFA date
June 13-17, 2014 At the ADA Meeting: Phase III data for NB32 related to fasting blood glucose levels and
other metabolic parameters in pre-diabetics.
Late June/early
July 2014
U.S. launch of Contrave
Q3 (July) 2014 CHMP Opinion or 180-Day Questions
Late Q3
(September) 2014
If there are 180-Day Questions, OREX to file responses within ~30 calendar days.
Late Q4 2014 EC decision (60 to 90 days following the CHMP meeting).
Q4 2014/Q1 2015 2nd interim analysis of the LIGHT Study (50% of events).
H2 2014+ License ex-U.S. rights for Contrave to a partner for obesity and/or Type 2 diabetes.
Late 2014+/H1
2015
Initiate Phase III, 26-week monotherapy and combination study of Contrave in Type 2
diabetes (paced by partnership?).
Q3+ 2015 Complete enrollment of Phase III Contrave Type 2 diabetes study.
Q4 2015/Q1 2016 3rd interim analysis of the LIGHT Study (75% of events).
Early 2016 Last patient, last visit in Phase III Type 2 diabetes study (~six months post last patient
recruited).
Q2 2016+ Top-line Phase III Type 2 diabetes study results.
H2 2016 File for regulatory approvals of Contrave in Type 2 diabetes.
End 2016+ Complete the LIGHT Study and report top-line results.
2017 Submit LIGHT Study results to regulatory authorities for inclusion in various package inserts.
Q2 2017 (U.S.)/
H2 2017 (Europe)
Regulatory decisions for Contrave as monotherapy or in combination with other Type 2
diabetes agents and as part of an FDC (with a DPP-IV inhibitor).
Late 2017/2018 Label expansion for Contrave to include the LIGHT Study CVOT results.
2022 Januvia/Janumet loses IP protection on a global basis (In 2026 for the salt formulation).
2014+ License rights to a partner.
2015+ Commence Phase III program.
Empatic
Source: Company reports and Wells Fargo Securities, LLC estimates
NB32 (Contrave)

WELLS FARGO SECURITIES, LLC
Orexigen Therapeutics, Inc. EQUITY RESEARCH DEPARTMENT

3

Exhibit 2. Income Statement
Orexigen Therapeutics, Inc. (OREX)
Statement of Operations Matthew J. Andrews (617) 603-4218
FYEnds December 31
(In million $'s except per share amounts)
Q1:14A Q2:14E Q3:14E Q4:14E
U.S. NB32 sales estimate (probability-weighted by indication) $6.1 $6.2 $12.5 $24.7 $124 $200 $306 $609 $903 $1,185
Revenues
NB32 net product sales (royalty to Orexigen) - - - $1.2 $1.2 $2.5 $4.9 $24.7 $40.1 $76.6 $182.7 $271.0 $414.7
Takeda collaborative revenue $3.4 $3.4 $0.9 $101.2 $0.9 $0.9 $103.7 $48.4 $18.4 $93.4 $103.4 $128.4 $153.4
Total Revenue $3.4 $3.4 $0.9 $102.4 $2.1 $3.3 $108.7 $73.2 $58.5 $170.0 $286.2 $399.4 $568.2
Expenses
Cost of Goods Sold - - - $0.1 $0.1 $0.2 $0.4 $2.2 $3.5 $5.4 $10.7 $15.8 $20.7
Research & Development $73.7 $56.7 $17.0 $18.0 $10.5 $10.5 $56.0 $45.0 $40.0 $40.0 $40.0 $35.0 $35.0
Selling General & Administrative $20.0 $23.9 $7.0 $6.5 $6.5 $6.5 $26.5 $30.0 $35.0 $40.0 $45.0 $50.0 $55.0
Total Operating Expenses $93.7 $80.6 $24.0 $24.6 $17.1 $17.2 $82.9 $77.2 $78.5 $85.4 $95.7 $100.8 $110.7
Operating Income (Loss) ($90.2) ($77.2) ($23.2) $77.8 ($15.0) ($13.9) $25.7 ($4.0) ($20.0) $84.7 $190.5 $298.6 $457.4
Interest Income & Other $0.15 ($0.5) ($1.7) ($1.6) $0.0 ($1.6) ($4.9) ($1.6) $0.2 $5.3 $10.2 $17.6 $27.6
Income Before Taxes ($90.1) ($77.7) ($24.9) $76.2 ($15.0) ($15.4) $20.9 ($5.6) ($19.8) $90.0 $200.7 $316.2 $485.0
Income Tax Expense - - - - - - - - - - - $0.0 $72.8
Rate (%) - - - - - - - - - - - 0% 15%
Net Profit (Loss) ($90.1) ($77.7) ($24.9) $76.2 ($15.0) ($15.4) $20.9 ($5.6) ($19.8) $90.0 $200.7 $316.2 $412.3
Other comprehensive loss $0.02 ($0.02) $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0 $0.0
Net Profit (Loss) Avail to Common ($90.1) ($77.7) ($24.9) $76.2 ($15.0) ($15.4) $20.9 ($5.6) ($19.8) $90.0 $200.7 $316.2 $412.3
Diluted EPS ($1.27) ($0.81) ($0.23) $0.48 ($0.11) ($0.11) $0.13 ($0.04) ($0.14) $0.54 $1.20 $1.86 $2.40
Taxed EPS ($1.27) ($0.81) ($0.23) $0.48 ($0.11) ($0.11) $0.13 ($0.04) ($0.14) $0.54 $1.20 $1.86 $2.40
Basic Shares 70.7 96.5 109.2 135.5 136.0 136.5 129.3 138.5 140.5 142.5 144.5 146.5 162.6
Diluted Shares 70.7 96.5 149.1 158.6 159.1 159.6 156.6 161.6 163.6 165.6 167.6 169.6 171.6
FY2012A FY2016E FY2017E FY2018E
Source: Company reports and Wells Fargo Securities, LLC estimates
FY2019E FY2020E FY2015E FY2013A 2014E FY2014E

WELLS FARGO SECURITIES, LLC
Biotechnology EQUITY RESEARCH DEPARTMENT


4

Exhibit 3. Pipeline Chart
Candidate Indication Stage And Summary
Obesity NDA re-submitted and under review/MAA under review - Contrave is a proprietary
fixed-dose combination of naltrexone sustained release (SR) and bupropion SR dosed in
two pills b.i.d. (8mg/90mg). Bupropion is a widely prescribed antidepressant and
smoking cessation medication and naltrexone is a treatment for alcohol and opioid
addiction. The Phase II program included 657 U.S. patients and the Phase III COR
Program included four studies: COR-I, COR-II, COR-Diabetes, and COR-BMOD and
evaluated three doses of naltrexone SR (16mg, 32mg, and 48mg) in combination with
bupropion SR 360mg. All studies were 56 weeks in length. For the proposed
commercial Contrave32 dose (naltrexone SR 32mg/bupropion SR 360mg), mean weight
loss (%), weight loss > 5%, and weight loss > 10% across the four studies ranged from
5.0-9.3%, 44.5%-66.4%, and 18.5%-41.5%, vs. 1.2%-5.1%, 16.4%-43%, and 5.7%-
20.2% for placebo. While an FDA EMDAC panel voted to recommend approval on
December 7, 2010, the FDA issued a Complete Response Letter in January 2011, based
primarily on its concerns regarding the cardiovascular safety profile of Contrave when
used over the long-term in overweight and obese subjects. Following consultation with
the FDA, Orexigen initiated the ~8,900 patient LIGHT CV outcomes study in June 2012.
Following an interim analysis of MACE events in Q4 2013, which ruled out an elevated
risk of CV events, Orexigen re-filed the NDA with the FDA in December 2013. In
September 2010, Oexigen entered into a collaboration agreement with Takeda to
develop and commercialize Contrave in the United States, Canada and Mexico. In
October 2013, Orexigen filed the MAA in the EU.
Type 2 Diabetes
Mellitus
Phase III - As part of the COR Program, Orexigen conducted COR-Diabetes (formerly
NB-304) which compared Contrave with placebo in 505 obese diabetics. After 56
weeks, Contrave patients demonstrated a 0.6% reduction in HbA1c vs. 0.1% for
placebo. Orexigen's development program includes plans to co-formulate Contrave
with a DPP-IV inhibitor, and it expects that a single Ph. III 26-week study should be
sufficient to obtain approval. It is unclear which DPP-IV inhibitor would be used, though
Takeda's Nesina (alogliptin; q.d.), which was approved in August 2013 could be most
likely due to its partnership with Takeda. Approval for the treatment of T2DM may
enable better formulary coverage by U.S. private managed care health plans.
Smoking cessation Phase II - Orexigen has completed a 24-week, open-label study of Contrave32 in 30
obese/overweight smokers. Smoking abstinence rates at week 12 and 24 were 48.1%
and 40.7%, respectively, and no clinically meaningful weight gain was observed. No
SAEs occurred and five patients withdrew due to AEs.
Depressed obesity Phase II - Orexigen has completed a 24-week, open-label study of Contrave32 in 25
obese/overweight patients with major depression. At weeks 12 and 24, Contrave32
resulted in mean decreases in Montgomery-Asberg Depression Rating Scale total scores
of more than 50%. AEs tended to be moderate in severity, no SAEs were observed,
and ten patients withdrew due to AEs.
Empatic
(bupropion/
zonisamide)
Obesity Phase II - Empatic is a novel combination of bupropion SR/zonisamide SR and is
currently on clinical hold pending the outcome of the Contrave NDA. Zonisamide, in an
immediate release formulation, was approved in the U.S. for the adjunctive treatment
of partial seizures, a form of epilepsy. Future development will be contingent upon
Orexigen licensing the compound. Ph. II(b) data demonstrate after 24 weeks that
Empatic120 and Empatic360 resulted in 6.1% and 7.5% weight loss compared to 1.4%
for placebo (based on ITT analysis).
OREX-003
Mitigation of weight
gain due to
antipsychotics
Phase II - OREX-003 is a combination of olanzapine/zonisamide SR. A planned Phase
II Proof-of-Concept study was placed on clinical hold in December 2008.
OREX-004
Obsessive-
compulsive disorder
Phase II - OREX-004 is a combination of naltrexone SR/fluoxetine. A planned Phase II
Proof-of-Concept study was placed on clinical hold in December 2008.
Orexigen Therapeutics, Inc.'s Pipeline Summary
Source: Company reports and Wells Fargo Securities, LLC
NB32
(Contrave;
naltrexone SR/
bupropion SR)



WELLS FARGO SECURITIES, LLC
Orexigen Therapeutics, Inc. EQUITY RESEARCH DEPARTMENT

5

Required Disclosures



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Orexigen Therapeutics, Inc. (OREX) 3-yr. Price Performance Orexigen Therapeutics, Inc. (OREX) 3-yr. Price Performance
Date


Date PublicationPrice($) RatingCode Val. Rng. Low Val. Rng. High ClosePrice($)
4/23/2014 5.53 1 11.00 12.00 5.54
4/24/2014 Andrews

Source: Wells FargoSecurities, LLCestimates andReuters data

Symbol Key RatingCodeKey
RatingDowngrade Initiation, Resumption, Dropor Suspend 1 Outperform/Buy SR Suspended
RatingUpgrade Analyst Change 2 Market Perform/Hold NR Not Rated
ValuationRangeChange Split Adjustment 3 Underperform/Sell NE NoEstimate



Additional Information Available Upon Request

I certify that:
1) All views expressed in this research report accurately reflect my personal views about any and all of the subject securities or
issuers discussed; and
2) No part of my compensation was, is, or will be, directly or indirectly, related to the specific recommendations or views expressed
by me in this research report.

Wells Fargo Securities, LLC maintains a market in the common stock of Orexigen Therapeutics, Inc.

OREX: Key risks are clinical and regulatory failures of NB32 in obesity and T2DM, obesity competition, and poor U.S.
reimbursement.

Wells Fargo Securities, LLC does not compensate its research analysts based on specific investment banking transactions.
Wells Fargo Securities, LLCs research analysts receive compensation that is based upon and impacted by the overall profitability
and revenue of the firm, which includes, but is not limited to investment banking revenue.

WELLS FARGO SECURITIES, LLC
Biotechnology EQUITY RESEARCH DEPARTMENT


6

STOCK RATING
1=Outperform: The stock appears attractively valued, and we believe the stock's total return will exceed that of the market over the
next 12 months. BUY
2=Market Perform: The stock appears appropriately valued, and we believe the stock's total return will be in line with the market
over the next 12 months. HOLD
3=Underperform: The stock appears overvalued, and we believe the stock's total return will be below the market over the next 12
months. SELL

SECTOR RATING
O=Overweight: Industry expected to outperform the relevant broad market benchmark over the next 12 months.
M=Market Weight: Industry expected to perform in-line with the relevant broad market benchmark over the next 12 months.
U=Underweight: Industry expected to underperform the relevant broad market benchmark over the next 12 months.

VOLATILITY RATING
V = A stock is defined as volatile if the stock price has fluctuated by +/-20% or greater in at least 8 of the past 24 months or if the
analyst expects significant volatility. All IPO stocks are automatically rated volatile within the first 24 months of trading.

As of: May 8, 2014
50% of companies covered by Wells Fargo Securities, LLC
Equity Research are rated Outperform.
Wells Fargo Securities, LLC has provided investment banking
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companies.
48% of companies covered by Wells Fargo Securities, LLC
Equity Research are rated Market Perform.
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3% of companies covered by Wells Fargo Securities, LLC
Equity Research are rated Underperform.
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companies.

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WELLS FARGO SECURITIES, LLC
Orexigen Therapeutics, Inc. EQUITY RESEARCH DEPARTMENT

7

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