JMP Securities Life Sciences Conference

June 24, 2015 NASDAQ: LGND

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The following presentation contains forward-looking statements regarding Ligand’s prospects, plans and strategies, drug development programs and collaborations. Forward-looking statements include financial projections, expectations regarding our and our partners’ research and development programs, and other statements including words such as “will,“ “should,” “could,” “plan,” etc. Actual events or results may differ from Ligand’s expectations. For example, drug development program benefits may not be realized and there can be no assurance that Ligand will achieve its guidance in 2015 or thereafter or that third party research summarized herein is correct or complete. The forward-looking statements made in the presentation are subject to several risk factors, including, statements regarding intent, belief, or current expectations of Ligand regarding its internal and partnered programs, including Promacta™, Kyprolis®, and Duavee™ and related projected market sizes, Ligand’s reliance on collaborative partners for milestone and royalty payments, royalty and other revenue projections based on third party research, regulatory hurdles facing Ligand's and partners’ product candidates, uncertainty regarding Ligand's and partners’ product development costs, the possibility that Ligand's and partners’ drug candidates might not be proved to be safe and efficacious and commercial performance of Ligand's and/or its partners’ products, risks related to Ligand’s internal controls, its compliance with regulations, accounting principles and public disclosure, and other risks and uncertainties described in its public filings with the Securities and Exchange Commission, available at www.sec.gov. Additional risks may apply to forward-looking statements made in this presentation. Readers are cautioned not to place undue reliance on these forward-looking statements, which reflect our good faith beliefs (or those of the indicated third parties) and speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, and Ligand undertakes no obligation to revise or update this presentation to reflect events or circumstances or update third party research numbers after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Securities Exchange Act of 1934. Our trademarks, trade names and service marks referenced herein include Ligand and Captisol. Each other trademark, trade name or service mark appearing in this presentation belongs to its owner. The process for reconciliation between non-GAAP financial numbers presented on slide 12, and the corresponding GAAP figures is explained in the footnotes on that slide and a full reconciliation can be found in our earnings press release dated, May 11, 2015.

Safe Harbor Statement

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Ligand: 2015 and Beyond

• Ligand is a high-growth company with economic rights to some of the world’s most important medicines

• Largest portfolio in company history and projected to continue to drive the business significantly

• Cutting-edge innovations with Captisol and LTP technology are making major drugs possible

• Well positioned for strong revenue and profitability growth

Ligand Fast Facts

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Portfolio Size

Blockbusters

Catalysts

Outlook

Over 120 fully-funded programs

Currently 2: Promacta® and Kyprolis®

6 major programs highlighted

Over 20 revenue-generating products expected by 2020

Financials Revenue

Cash Flow

Repurchase

> 30% annualized growth projected

High due to low costs and low taxes

1.25 mil shares (6%) during 2H 2014

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2015 Events are Transforming Ligand

Date Program Event

January Delafloxacin Phase 3 study - Positive interim results

January Sparsentan Orphan drug designation - Focal Segmental Glomerulosclerosis

January Kyprolis US and EU submissions - Relapsed Multiple Myeloma

February Lasofoxifene Sermonix licensing agreement

February Promacta EU submission - Pediatric ITP

March Kyprolis Phase 3 ENDEAVOR study - Positive results

March Promacta Promacta acquisition closed (GSK to Novartis)

March Kyprolis Priority FDA review - Relapsed Multiple Myeloma

April SAGE-547 Phase 1/2 completion; Phase 3 trial initiated

April IRAK-4 Positive preclinical data presented

May Multiple Selexis 15+ program portfolio acquisition

June LGD-6972 Positive Phase 1b results

June Kyprolis Phase 3 ARROW study initiation for once-weekly dosing

June Promacta sNDA approval - Pediatric ITP

0

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2008 2015

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Ligand’s Portfolio Continues to Grow

120 +

0

20

40

60

80

100

120

2008 2015

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Ligand’s Achievement: Portfolio Expansion

Partners’ Achievement: Products Generating Revenue for LGND

Excellent record as drug researcher, innovator and licensor

Our partners are doing their job getting new products to the market

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Diverse Capital Allocation Building Asset Base and Increasing Returns for Investors

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• Over last several years, Ligand has deployed capital in the following ways

— Company acquisitions

— Royalty acquisitions

— Share buybacks

— Investment in a private company that has completed its IPO

— Invested in development of new technology platforms

• Ligand takes advantage of market knowledge and experience gained from our partnerships to find opportunities to invest and create value from the biopharma industry

• We will continue to explore opportunities that our programs and the markets present us

Technology and Novel R&D Drive Deal Making

Potential Launch

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Our Platform Technologies

Our Novel R&D

LTP Technology™

Glucagon Receptor Antagonist Program for Diabetes Entering Phase 2

Positive Phase 1b data showing robust effects throughout multiple ascending dosing

Solving solubility and stability challenges

Designed to selectively deliver broad range of pharmaceutical agents to the liver

Oral GCSF Preclinical Leveraging our technology and heritage in small molecule discovery

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20 Products by 2020 Significant Expansion of Revenue Generating Assets Projected

• Over 20 commercial programs projected to be generating revenue for Ligand by the end of this decade

• Programs expected to come from existing portfolio; no new deals required to drive that expansion

2008 2014 2020Projected

1

7

> 20

Ligand’s Revenue Generating Assets

Biotech44%

Big Pharma29% Generic

18%

Spec Pharma10%

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Over 70 Partners

Select Big Pharma

Select Biotech

Select Spec Pharma

Select Generic

Diverse Portfolio Among Drug Companies

• We estimate our partners will spend over $1.1 billion in 2015 on R&D to advance our programs

• More partnered programs and late-stage trials are pushing spending up over 30% higher than 2014

Fully-funded Partnerships Driving Growth

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– 13 Phase 3 trials – 14 preclinical programs

– 38 Phase 2 trials – Manufacturing scale-up

– 58 Phase 1 trials – Regulatory filing fees

– 2 Phase 4 trials

Financial Overview

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• Continued strong financial performance

• Accelerating projected revenue, earnings and cash flow growth

• Business model provides tremendous earnings leverage

— Growing total revenues: 33% compound annual growth projected 2015-2017

— Robust margins: 2014 gross margins ~86%, adjusted cash flow margins ~50%

— Strong earnings growth: 2017 adjusted EPS projected to be >$4.45 compared to $1.52 in 2014

— Significant estate of tax assets: Over half a billion dollars in NOLs, projected cash tax rate to be below 5% for next several years

Adjusted EPS excludes non-cash expenses such as SBC, CVRs and convertible debt expense

Commercial Product

Highlights

• Oral medicine that boosts platelets. Ligand owed royalties

• Long patent protection, Orange Book patent expiration in 2027

• Blockbuster commercial potential (>$1 billion) due to growing and large list of potential therapeutic indications

ITP HCV ORT Idiopathic

Thrombocytopenia

Thrombocytopenia Induced by Hepatitis C

Oncology Related

Thrombocytopenia

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Promacta®: Blockbuster Commercial Potential

Aplastic Anemia

95 Countries

Filed in the EU Recent approval for

Pediatric ITP

53 Countries

Global filing and launch investment

Major clinical investment ongoing: MDS, AML, CLL, CIT,

others

AA Currently Approved Indications

Ongoing Development New Markets

3 Countries

70

85

GSK Novartis

1,300

8,000

GSK Novartis

$2.0

$11.7

GSK Novartis

GSK and Novartis: Business Unit Profiles1

Novartis has a superior oncology business, ~6 times larger than GSK’s; Promacta® transitioned to Novartis on March 1st

Oncology Employees Countries with Presence 2014 Oncology Revenue ($B)

15 Reference: GSK and Novartis company disclosures; GSK.com, Novartis.com

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• Leading 3rd-line treatment for multiple myeloma (MM) in the US

— Viewed as best-in-class proteosome inhibitor

Kyprolis®

• Royalty rates of 1.5% to 3.0%

ENDEAVOR Data

Dr. Meletios A. Dimopoulos University of Athens

“The combination of carfilzomib and dexamethasone was superior to bortezomib and dexamethasone regardless of age or prior bortezomib exposure and represents a new standard of care.”

• Amgen has submitted US and EU applications for 2nd line treatment in relapsed MM

— Granted priority FDA review; July 26, 2015 PDUFA date — Also granted EU Accelerated Assessment

• Major investment by Amgen focused on further expansion of the label

— First-Line MM: Phase 3 (CLARION) — Once-Weekly Dosing: Phase 3 (ARROW) — Small-cell Lung Cancer: Phase 2

Reference: AMGN March 2, 2015 corporate presentation 17

• Recent data and events have continued to demonstrate the significant potential of Kyprolis

Kyprolis®

• APSIRE Phase 3 trial demonstrated an unprecedented 26.3 months of progression free survival (PFS) in relapsed MM

• ENDEAVOR Phase 3 trial demonstrated a DOUBLING of median PFS over Velcade® (18.7 vs. 9.4 months) in relapsed MM

— 2014 worldwide Velcade sales were $3.1 billion

• Significant unmet needs remain in MM, and the market is expected to double to over $13 billion by 2020

Kyprolis® Growth Trends

• 16 Amgen analysts provide projections for Kyprolis

• Consensus estimates project sales to increase ~5x by 2020

• Kyprolis has shown superior efficacy over Velcade1, the leading competitor which sold $3.1 billion in 2014

• On higher revenues, Ligand receives higher royalties

$0

$500

$1,000

$1,500

$2,000

$2,500

$3,000

2012 2013 2014 2015 2016 2017 2018 2019 2020

Low Analyst Estimate

High Analyst Estimate

Consensus

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$ m

illio

ns

Reference: Amgen ENDEAVOR results press release, dated March 1, 2015

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec Jan Feb Mar Apr May

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DUAVEE™

• Product for post-menopausal hot flashes and osteoporosis

• Significant US prescription growth trend

• Potential EU launch in 2015

• Ligand is owed tiered royalties from 0.5%-2.5%

US Monthly Prescriptions

2014 2015

DTC Campaign Initiated

Reference: Bloomberg/Symphony Health

Reference: Q2’15 based on Baxter Q1’15 royalty report to Ligand

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Rev

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Nexterone: Royalty Revenue

$0

$20

$40

$60

$80

$100

$120

$140

$160

$180

$200

Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2

2012 2013

• Captisol-enabled product for treatment of ventricular fibrillation

• Shown consistent significant growth over recent quarters

• Baxter is dedicated to the brand and is pursuing expansion

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2014 2015

The Big Six

• Certain portfolio assets stand above others, having the potential to add significantly to Ligand’s top and bottom line

• They do so as a result of a mixture of factors, including:

— Market size or therapy area addressed

— Upcoming potential milestone events

— Royalty rate or specifics of deal economics

• Major news catalysts expected over the next 6 to 24 months

• More potential programs could move into the Big Six

The Big Six: Major Pipeline Assets

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Partner

Program (Therapy Area)

Stage

Royalty Rate

Potential Launch

Potential or Actual 2015 Events

EVOMELA (Oncology)

NDA

20% 2015 Pending Approval

Delafloxacin IV (Infection)

Phase 3 Undisclosed 2016 Phase 3 Data

Reported

SAGE-547 (Neurology)

Phase 3 Undisclosed 2017 Phase 3 Trial

Initiated

Sparsentan (FSGS - Kidney Disease)

Phase 2 9% 2017 Enrollment

Completion by YE

MK-8931 (Alzheimer’s Disease)

Phase 3 Undisclosed 2018 Updates

IRAK-4 (Oncology)

Preclinical 6.0-9.5% 2019 Clinical Start by YE

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The Big Six: Major Pipeline Assets

Viking Therapeutics

VKTX: Company Overview

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• San Diego-based biotech, developing novel, first-in-class or best-in-class drugs for metabolic disorders

• Company went public in April 2015 and Ligand has 5 licensed programs with Viking

• Leading clinical-stage programs with preliminary efficacy signals in humans

SARM Non-steroidal selective

androgen receptor modulator

Entering Phase 2 Development for Hip Fracture

Data Expected 2Q 2016

TR-β Novel, Selective thyroid

receptor-β Agonists

Strong scientific rationale for application in X-ALD with potential

Human POC data in 1H 2016

Additional opportunities in NASH and cholesterolemia

LGD-6972:

Glucagon Receptor

Antagonist (GRA)

LGD-6972: Program Overview

• Ligand is currently developing LGD-6972, a glucagon receptor antagonist (GRA) entering Phase 2

• Glucagon receptor antagonism is a novel approach for the treatment of diabetes

• Many traditional therapies target insulin, a pancreatic hormone which reduces blood glucose

— Administration of insulin increases glucose storage in the liver and glucose utilization in tissues and therefore reduces blood glucose

• LGD-6972 blocks the action of glucagon, a pancreatic hormone which increases blood glucose

— Blocking the glucagon receptor decreases the liver’s ability to release glucose, and therefore reduces blood glucose

27 Phase 2 trial expected to begin in 2016

LGD-6972: Positive Phase 1b Results

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• Ligand recently completed a multiple ascending dose phase 1b trial for LGD-6972

• Results showed that LGD-6972 has an favorable safety profile

• Dose-dependent decreases were seen in fasting plasma glucose in both healthy volunteers and Type 2 diabetics (maximal decrease of 60 mg/dL)

Fasting Plasma Glucose Reduction in Type 2 Diabetics

• Decreased glucose was noted in both fasting and post-prandial states (approximate decrease in weighted mean glucose > 50 mg/dL)

• Ligand advancing program to initiate a Phase 2 trial for LGD-6972 in 2016

Major Global Market for Diabetes Drugs

2013 2022E

$38 B

$68 B

• One of the largest drug categories

• Global market projected to grow to $68 billion by 2022, over 75% increase in 10 years

• Significant opportunity for novel treatment mechanisms

• Over the past 5 years there have been 32 licensing deals (pre-clinical to Phase 3) in diabetes with disclosed deal payments of >$11 billion

• Combination therapy highly prevalent and necessary to optimize management of the disease

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Sources: EvaluatePharma June 2014; Global Data: Type 2 Diabetes-Global Drug Forecast & Market Analysis to 2022 and Thomson Reuters Cortellis

Top 10 Non-Insulin Diabetes Drugs

30 Source: Thomson Reuters Cortellis - 2020 sales based on analyst consensus projections, 2015

Mechanism

Drug

Company

2014 Sales ($ million)

DPP-IV Januvia Merck $3,900

GLP-1 Victoza Novo $2,400

DPP-IV Janumet Merck $2,100

DPP-IV Galvus Novartis $1,200

DPP-IV Onglyza Astra $820

GLP-1 Byetta/ Bydureon

Astra $767

SGLT-2 Invokana J&J $552

SGLT-2 Forxiga Astra $138

SGLT-2 Jardiance Eli Lilly/BI $15

GLP-1 Trulicity Eli Lilly $10

TOTAL 2014 SALES $12 B

Mechanism

Drug

Company

Est. 2020 Sales ($ million)

DPP-IV Januvia Merck $4,190

GLP-1 Victoza Novo $3,445

SGLT-2 Invokana J&J $3,300

DPP-IV Janumet Merck $2,800

DPP-IV Galvus Novartis $1,425

SGLT-2 Forxiga Astra $1,300

GLP-1 Trulicity Eli Lilly $1,100

DPP-IV Onglyza Astra $851

GLP-1 Byetta/ Bydureon

Astra $810

SGLT-2 Jardiance Eli Lilly/BI $620

TOTAL Est. PEAK SALES ~$20 B

Current Top 10 - 2014 Sales Top 10 - Estimated 2020 Sales

• Market projected to grow over 65% to ~$20 billion in 2020

• 7 products in category projected to have sales greater than $1 billion

Advantages of Potent GRA

Existing Class

Product Profile GRA Advantage GRA Potentially

Competitive with Class

Potential GRA Combo with

Class

DPP-IV Modest reduction of plasma glucose

Expected higher glucose

reduction √ √

GLP-1 Only available as

injectables Oral √ √

SGLT-2

Contraindicated for renally impaired patients, safety considerations

Potentially effective in

renally impaired

√ √

Product profile and recent clinical data suggest significant market advantages for a safe, highly potent, oral GRA

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Potential Upcoming Events

Target Date Program Event

Q2’15 Duavive EU product pricing/launch

7/26/15 Kyprolis Multiple Myeloma sNDA PDUFA date

2H’15 Promacta Pediatric ITP MAA approval

2H’15 Kyprolis Relapsed multiple myeloma MAA approval

2H’15 NS-2 Phase 2 trial initiation

2H’15 Delafloxacin NDA Submission

10/23/15 EVOMELA NDA PDUFA date

Q4’15 Promacta Severe Aplastic Anemia MAA approval

Q4’15 Carbella NDA approval

Q4’15 Topiramate Phase 2 trial initiation

Q4’15 IRAK-4 Phase 1 trial initiation

JMP Securities Life Sciences Conference

June 24, 2015 NASDAQ: LGND