Copyright © 2016 Actelion Pharmaceuticals Ltd

STRONG PERFORMANCE CONTINUES

Financial Reporting Investor Webcast 21 July 2016

© 2016 Actelion Pharmaceuticals Ltd

The following information contains certain “forward-looking statements”, relating to the company’s business, which can be identified by the use of forward-looking terminology such as “estimates”, “believes”, “expects”, “may”, “are expected to”, “will”, “will continue”, “should”, “would be”, “seeks”, “pending” or “anticipates” or similar expressions, or by discussions of strategy, plans or intentions. Such statements include descriptions of the company’s investment and research and development programs and anticipated expenditures in connection therewith, descriptions of new products expected to be introduced by the company and anticipated customer demand for such products and products in the company’s existing portfolio. Such statements reflect the current views of the company with respect to future events and are subject to certain risks, uncertainties and assumptions. Many factors could cause the actual results, performance or achievements of the company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Where figures are given, rounding errors may occur.

H1 2016 Financial Results 2

© 2016 Actelion Pharmaceuticals Ltd

TRANSFORMING ACTELION

Excellent performance across all areas of business

Products: Strong sales of Opsumit & Uptravi

Innovation: Significant pipeline progression

Finance: Upgraded guidance

H1 2016 Financial Results 3

H1 2016

© 2016 Actelion Pharmaceuticals Ltd 07 Jul 2016 Investor webcast 4

Compound Indication Study Status

Phase III

Cadazolid Clostridium difficile-associated diarrhea IMPACT Ongoing

Macitentan Eisenmenger syndrome MAESTRO Ongoing

Macitentan Pediatric PAH TOMORROW Initiating

Ponesimod Multiple sclerosis OPTIMUM Ongoing

Phase II

Clazosentan Reversal of vasospasm associated with aneurysmal subarachnoid hemorrhage REVERSE Ongoing

Cenerimod Systemic lupus erythematosus - Ongoing

Dual Orexin Receptor Antagonist Insomnia - Initiating

Endothelin Receptor Antagonist Specialty cardiovascular disorders - Ongoing

Macitentan Chronic thromboembolic pulmonary hypertension MERIT Ongoing

Macitentan Combined pre- and post-capillary pulmonary hypertension MELODY Complete

Ponesimod Graft-versus-host disease - Ongoing

Phase Ib Lucerastat Fabry disease - Complete

Phase I

New Chemical Entity Cardiovascular disorders - Ongoing

Selective Orexin 1 Receptor Antagonist Neurological disorders - Ongoing

T-type Calcium Channel blocker Neurological disorders - Ongoing

© 2016 Actelion Pharmaceuticals Ltd 07 Jul 2016 Investor webcast 5

Compound Indication Study Status

Phase III

Cadazolid Clostridium difficile-associated diarrhea IMPACT Ongoing

Macitentan Eisenmenger syndrome MAESTRO Ongoing

Macitentan Pediatric PAH TOMORROW Initiating

Ponesimod Multiple sclerosis OPTIMUM Ongoing

Phase II

Clazosentan Reversal of vasospasm associated with aneurysmal subarachnoid hemorrhage REVERSE Ongoing

Cenerimod Systemic lupus erythematosus - Ongoing

Dual Orexin Receptor Antagonist Insomnia - Initiating Endothelin Receptor Antagonist Specialty cardiovascular disorders - Ongoing

Macitentan Chronic thromboembolic pulmonary hypertension MERIT Ongoing

Macitentan Combined pre- and post-capillary pulmonary hypertension MELODY Complete

Ponesimod Graft-versus-host disease - Ongoing

Phase Ib Lucerastat Fabry disease - Complete

Phase I

New Chemical Entity Cardiovascular disorders - Ongoing

Selective Orexin 1 Receptor Antagonist Neurological disorders - Ongoing

T-type Calcium Channel blocker Neurological disorders - Ongoing

© 2016 Actelion Pharmaceuticals Ltd

Core operating income growth in the low-teen percentage range at constant exchange rates and barring unforeseen events

2016 FINANCIAL GUIDANCE UPGRADE

H1 2016 Financial Results 6

© 2016 Actelion Pharmaceuticals Ltd

TURBO-CHARGING THE PORTFOLIO TRANSFORMATION

H1 2016 Financial Results 7

© 2016 Actelion Pharmaceuticals Ltd

1,008 1,179

H1 2015 H1 2016

SUSTAINED STRONG PERFORMANCE

H1 2015 H1 2016

US 49% 54%

Europe 33% 27%

Japan 9% 10%

RoW 10% 9%

H1 2016 Financial Results 8

+13% at CER

CHF million

H1 2016

© 2016 Actelion Pharmaceuticals Ltd

THE TRANSFORMATION IS PROGRESSING WELL

44%

47%

9%

61% 27%

12%

77%

11%

12%

Others Tracleer Opsumit + Uptravi + Veletri

H1 2016 Financial Results 9

Q2 2014 CHF 487m*

Q2 2015 CHF 493m

CHF million

Q2 2016 CHF 590m

* Excludes US rebate reversals

H1 2016

© 2016 Actelion Pharmaceuticals Ltd 10

Oral prostacyclin analogue (n=30)

20% 53% 20% 7% 23% 43%

HIGH PROPENSITY TO PRESCRIBE PRE-LAUNCH IN THE US

Source: In-house qualitative market research

27% 7%

Inhaled prostacyclin analogue (n=30)

80% Extremely / very suitable 67% Extremely / very suitable

© 2016 Actelion Pharmaceuticals Ltd

15

45 20

10

1

Q1 2016 Q2 2016

US Sales US inventory Ex-US sales

A POWERFUL START

11

CHF million

© 2016 Actelion Pharmaceuticals Ltd

POSITIVE CUSTOMER FEEDBACK

Vs. Oral Prostacyclin:

Stronger efficacy

Easier titration and easier patient education

Less side effects

Better dosing schedule

Support material is working very well

12

© 2016 Actelion Pharmaceuticals Ltd 13

4% 4%

36% 57%

HIGH PROPENSITY TO PRESCRIBE

Source: In-house qualitative market research

93% Highly / Very likely

Future intent to prescribe among physicians that have not yet prescribed Uptravi (n=28)

Very likely to prescribe (9-10)

Not at all likely to prescribe (1-2)

7-8

5-6

3-4

© 2016 Actelion Pharmaceuticals Ltd

5 15 38

59 68 95

113 147 162 178

200

Q4 2013 Q1 2014 Q2 2014 Q3 2014 Q4 2014 Q1 2015 Q2 2015 Q3 2015 Q4 2015 Q1 2016 Q2 2016

SUSTAINED SALES GROWTH DYNAMICS

14

CHF million

© 2016 Actelion Pharmaceuticals Ltd

CONTINUED SIGNIFICANT GROWTH

Growth continues due to:

– Launch momentum in France continuing in 2016

– Japan* +10% despite a 12% price cut on 1 March 2016

Competitor product RT stable Flolan launched in Japan – US/EU launch expected in H2 2016

38 48

H1 2015 H1 2016

+19% CER Growth

CHF million

15

*Trade name Epoprostenol “ACT”

© 2016 Actelion Pharmaceuticals Ltd

TRANSITIONING TO OPSUMIT Dynamics driven by Opsumit, Generic impact

in selected markets and DU growth

US price increase almost balances erosion ex-US

Impact of order phasing and inventory adjustments in US

Generic Update:

– Spain: strong generic competition

– US: Shared REMS in final stages of development

645 546

H1 2015 H1 2016

CHF million

16

- 16% in Volume -18% at CER

H1 2016 Financial Results

© 2016 Actelion Pharmaceuticals Ltd

MANAGED DECLINE

34% decline in units shipped due to competitive environment

Volume decline expected to accelerate due to competitive situation

No generic entry expected in 2016 57

43

H1 2015 H1 2016

CHF million

17

-27% CER Variance

H1 2016 Financial Results

© 2016 Actelion Pharmaceuticals Ltd

44 52

H1 2015 H1 2016

CONTINUED GROWTH IN NP-C (ex-US)

2015 baseline effect in the US

Increasing generic competition for GD1 in selected EU markets

Strong growth (+14%) in NP-C indication ex-US (i.e. Japan*, France, Canada, Brazil)

Miglustat generic entry in US during H2 2016 not to be excluded

+15% CER Growth

CHF million

18 H1 2016 Financial Results

*Trade name Brazaves

© 2016 Actelion Pharmaceuticals Ltd

W

CONSISTENT PROGRESS

H1 2016 sales: CHF 18 million

ATU FR proceeding well: 258 patients by end of H2 2016

Regulatory process ongoing – EU* decision anticipated early in 2017

19 H1 2016 Financial Results

0

1,000

2,000

3,000

4,000

Q1-15 Q2-15 Q3-15 Q4-15 Q1-16 Q2-16

US units sold Ex-US units sold

*Trade name Ledaga®

© 2016 Actelion Pharmaceuticals Ltd 20

Build on strong early launch trajectory for Uptravi in the US

Manage generic exposures

Execute Uptravi launches ex-US

Continue Opsumit trajectory

PRIORITIES FOR H2 2016: FOCUS ON EXCELLENCE IN EXECUTION

H1 2016 Financial Results

© 2016 Actelion Pharmaceuticals Ltd

STRONG FINANCIAL PERFORMANCE

H1 2016 Financial Results 21

© 2016 Actelion Pharmaceuticals Ltd H1 2016 Financial Results 22

STRONG FIRST HALF 2016

Variance

H1 2015 H1 2016 CHF CER

Product sales CHF million

1,008 1,179 17% 13%

Core operating income CHF million

423 499 18% 11%

Core diluted EPS CHF

3.11 4.05 30% 23%

Operating income CHF million

344 412 20% 12%

US GAAP diluted EPS CHF

2.50 3.32 33% 23%

H1 2016

© 2016 Actelion Pharmaceuticals Ltd

PRODUCT SALES INTRINSIC GROWTH + 13%

1,008 1,140 1,179

132 39

H1'15 Sales H1 '16 intrinsic sales growth

FX H1'16 Sales

H1 2016

CHF million

H1 2016 Financial Results 23

© 2016 Actelion Pharmaceuticals Ltd

CORE OPERATING INCOME INTRINSIC GROWTH + 11%

H1 2016

423 470 499

47 29

H1'15 Core operating income H1 '16 intrinsic growth FX H1'16 Core operating income

CHF million

H1 2016 Financial Results 24

© 2016 Actelion Pharmaceuticals Ltd

CORE OPERATING INCOME

1,179

499 499

92

250

338

H1 '16 Product sales Cost of sales R&D SG&A H1 '16 Core operatingincome

H1 2016

CHF million

H1 2016 Financial Results 25

© 2016 Actelion Pharmaceuticals Ltd

US GAAP OPERATING INCOME

499 412 412

344

44 32

11

H1'16 Core operatingincome

D&A Stock-basedcompensation

Other H1'16 OperatingIncome

H1'15 OperatingIncome

H1 2016

CHF million

H1 2016 Financial Results 26

© 2016 Actelion Pharmaceuticals Ltd

US GAAP NET INCOME

CHF million

412 360 361

287

3 55 1

H1'16 OperatingIncome

Financial result Income taxes Non-controllinginterest

H1'16 Net Income H1'15 Net Income

H1 2016

H1 2016 Financial Results 27

© 2016 Actelion Pharmaceuticals Ltd

EARNINGS PER SHARE

Variance

H1 2015 H1 2016 CHF CER

Core Net income CHF million

357 440 23% 16%

Core Diluted EPS Number of shares in calculation (m)

3.11 114.7

4.05 108.6

30% 23%

US GAAP Net income CHF million

287 361 25% 17%

US GAAP Diluted EPS Number of shares in calculation (m)

2.50 114.7

3.32 108.6

33% 23%

H1 2016

H1 2016 Financial Results 28

© 2016 Actelion Pharmaceuticals Ltd

CASH POSITION & CASH FLOW H1 2016

405 531

418 418 472 418

420

159

135 113 19 19

Net cash31 Dec 15

Operatingcash flow

Dividend 2nd line sharerepurchase

1st line sharepurchase

ESOPproceeds

Capex,other items

Net cash30 June 2016

H1 2016 Financial Results 29

CHF million

© 2016 Actelion Pharmaceuticals Ltd

Low-teen percentage core operating income growth, at constant exchange rates and barring unforeseen events

FINANCIAL GUIDANCE 2016

H1 2016 Financial Results 30

© 2016 Actelion Pharmaceuticals Ltd

TRANSFORMING ACTELION

Excellent performance across all areas of business

Products: Strong sales of Opsumit & Uptravi

Innovation: Significant pipeline progression

Finance: Upgraded guidance

H1 2016 Financial Results 31

H1 2016