1/24/2018

The IQOS Heating System

Tobacco Products Scientific Advisory Committee January 25, 2018

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Scientific Assessment

17 Non-Clinical Studies Studies 8 Clinical Studies

30+ on IQOS assessment Publications 150+ on assessment methods and verification

Hoeng et al. A Network-Based Approach to Quantify the Impact of Biologically Active Substances. Drug Discov. Today 2012; 17:413-418. Sturla et al. Systems Toxicology: from basic research to risk assessment. Chem. Res. Toxicol. 2014; 27:314-329. CC-118

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IQOS Usage Patterns Actual Use Study

IQOS and Cigarettes Use: Observational Period Actual Use Study

Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 n=1,106 n=1,061 n=1,038 n=1,009 n=977 n=968

100% IQOS 5% 6% 7% 7% 6% 6%

Exclusive Use: ]95-100%] IQOS 7% 8% 9% 8% 7% 8%

THS-PBA-07-US CC-119

IQOS In Market Usage Patterns Post-Market Consumer Panel Surveys

South Korea Japan Italy Germany Switzerland n=631 n=6925 n=4197 n=2249 n=2101

100% IQOS 63% 68% 57% 50% 47%

Exclusive Use: ]95-100%] IQOS 73% 72% 61% 55% 51%

CONSUMER PANEL SURVEYS. August 2017 CC-120

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PBA Studies to Develop and Assess IQOS Messages

Phase 1 Phase 2

Developing the most Assessing Labeling and appropriate product Advertising 6 messages qualitative and Comprehension quantitative studies Comprehension to develop and assess IQOS communications Intent to Use Intent to Use

Risk Perception Risk Perception

3 Studies 3 Studies

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The IQOS Opportunity

• Millions fewer smokers

• Reduced harm and tobacco-related disease

• An important step forward

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3 1/24/2018

Tobacco Products Scientific Advisory Committee

Sponsor backup slides shown

January 25, 2018

Human vs Machine-smoking Range

Distribution frequency of mouth level exposure Range covered by selected to nicotine measured for R&D panel of IQOS users smoking-machine regimens

>95% 45 40 35 30 25 20 15 Frequency 10 ISO LR-3 HCI 5 SR-1 SR-5 SR-4 SR-6 0 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2 2.4 Nicotine [mg/stick] AC-47

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HPHCs Response to Puffing Regime Reduction vs. cigarette is maintained

Linear “Plateau” Quadratic Flat

Pyrene, benzo[a]pyrene, Ammonia, acrylamide, NAT, NNK, isoprene, dibenzo[a,h]anthracene, ethylene oxide, styrene, toluene, benzene, 1-aminonaphtalene, acrylonitrile, pyridine, acetone, MEK, m-cresol, o-cresol, 2-aminonaphtalene, crotonaldehyde, acetaldehyde, butyraldehyde, p-cresol and quinoline 3-aminobiphenyl, acrolein,acetamide, hydroquinone, resorcinol, 4-aminobiphenyl o-toluidine and NAB and nitrogen oxides and vinyl chloride

AC-48

Systemic Toxicity – Lung inflammation Combined Chronic Toxicity and Carcinogenicity Study – A/J mice

MMP activity in BALF Neutrohil count in BALF SEM) MMPactivity (mU/ml,mean

Pigmented macrophages in the lung SEM) Pigmented macrophage Pigmented (severity score, mean score, (severity 3R4F IQOS (L) IQOS (M) IQOS (H) 3R4F IQOS (L) IQOS (M) IQOS (H)

Study number 15020 SD-1071

5 1/24/2018

IQOS In Market Usage Patterns Post-Market Consumer Panel Surveys

South Korea Japan Italy Germany Switzerland n=631 n=6925 n=4197 n=2249 n=2101

100% IQOS 63% 68% 57% 50% 47%

Exclusive Use: ]95-100%] IQOS 73% 72% 61% 55% 51%

CONSUMER PANEL SURVEYS. August 2017 XX-5

No Increase in IQOS and Cigarettes Consumption Between Baseline and Observational Period

Actual Use Study: IQOS + Cigarette Consumption

Predominant IQOS Use [70%-82.5%[ IQOS Use [82.5%-95%] IQOS use n=34 n=34

10 8.4 10 8.0 (Stick/Day–Total) (Stick/Day–Total) 8 8

6 6 6.0 10.2 8.9 6.7 4 4

2 2 2.4 1.4 Consumption (Stick/Day) 0 Consumption (Stick/Day) 0 Baseline Observational Baseline Observational

# of Cigarettes # of IQOS

THS-PBA-07-US XX-7

6