Tobacco Harm Reduction E-Vapor Products

Tobacco Harm Reduction

E-Vapor Products

Michael Fisher, Ph.D. June 8, 2018

1st Scientific Summit on Tobacco Harm Reduction

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 1 Cigarette Smoking: A Significant Public Health Problem

Cigarette smoking Cigarette Smokers’ life causes about smoking causes expectancy one of every an estimated is about five deaths 480,000 deaths 10 years shorter annually annually. than nonsmokers’ in the U.S

Source: http://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/tobacco_related_mortality/index.htm#cigs

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 2 Cigarette Smoking Trends Among U.S. Adults 1965 – 20151 A Healthy People 45 2020 objective is 40 12% smoking 2 35 prevalence.

20 ~40 15 million 10 Adult Smoking Rate (%) Adult Smoking Rate

0 1965 1967 1969 1971 1973 1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 2011 2013 2015

Year

1 http://www.cdc.gov/tobacco/data_statistics/tables/trends/cig_smoking/index.htm 2 https://www.healthypeople.gov/

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 3 FDA Recognizes Continuum of Risk

“We must recognize the potential for innovation to lead to less harmful products, which, under FDA’s oversight, could be part of a solution. While there’s still much research to be done on these products and the risks that they may pose, they may also present benefits that we must consider.”

Dr. Scott Gottlieb FDA Commissioner

Continuum of Risk

Combusted Tobacco Products Non-combusted Tobacco Products

MOST LEAST HARMFUL HARMFUL

July 28, 2017: Protecting American Families: Comprehensive Approach to Nicotine and Tobacco https://www.fda.gov/NewsEvents/Speeches/ucm569024.htm

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 4 Tobacco Harm Reduction at Altria

Our long‐term goal at Altria is to achieve a leadership position in innovative and reduced risk tobacco products.

Continuum of Risk

Combusted Tobacco Products Non-combusted Tobacco Products

MOST LEAST HARMFUL HARMFUL

July 28, 2017: Protecting American Families: Comprehensive Approach to Nicotine and Tobacco https://www.fda.gov/NewsEvents/Speeches/ucm569024.htm Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 5 Altria Supports Harm Reduction in a Variety of Ways

Developing & Help Reduce Supporting Communicating Marketing Underage Cessation about the health Lower-Risk Tobacco Use effects of Tobacco tobacco use Products

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 6 Harm Reduction Opportunities

~5 MM Adult Smokeless Consumers

~40 MM Adult Cigarette Smokers ~10 MM Adult E-Vapor Consumers

*Source: 18+ATCT 12MM ending December 2017 Numbers may not foot due to rounding

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 7 Noncombustible Tobacco Product Platforms

Oral Tobacco/ E-Vapor Heated Tobacco Nicotine Products Products

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 8 Diverse E-vapor Product Portfolio

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 9 FDA Market Pathways

Product Pathway Reduced Exposure or Reduced Risk Claim

Substantial Modified Risk Substantial Premarket Tobacco Equivalence Tobacco Product Equivalence Application Exemption Request Application “SE” or “905” “PMTA” or “910” “905(j)(3)” “MRTPA” or “911”

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 10 ALCS Framework for Reduced Harm Tobacco Products

Constituent Risk Reduction Harm Reduction Reduction Individual Population

Product Chemical Toxicology Studies in Perception Risks and Design and and Physical and Risk Adult Human and Behavior Benefits to the Control Characterization Assessment Subjects Assessment Population

The Product Exposure and Health Risk Impact on the Population

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final11 | 11 ALCS Framework for Reduced Harm Tobacco Products

Constituent Risk Reduction Harm Reduction Reduction Individual Population

The Product Exposure and Health Risk Impact on the Population

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final12 | 12 ® Product Design MarkTen Product was Designed to and Control Eliminate or Significantly Reduce Chemical 1 and Physical HPHC Generation Characterization Cartridge Puff sensor Heated coil

Battery Vent holes Mouth piece

• Selection and evaluation of individual components and ingredients Product Design and Controls • Manufacturing standards and quality controls • Product stability • Battery safety Chemical and Physical Characterization Elimination or reduced formation • Selected HPHC • Other targeted constituents (e.g. metals) 1 HPHC = Harmful or Potentially Harmful Constituents

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 13 Chemical Harmful and Potentially Harmful Constituents in and Physical MarkTen® Aerosol Are Substantially Lower Than Characterization Reference Cigarettes Volatile Aromatic Organic Percentage CarbonylsCarbonyls B(a)P B(a)P AromaticAmines AminesCompounds VOCsTSNAs TSNAs Change 100%0 Compared to Reference Cigarette 3R4F

> 99% ~100% ~100% ~100% ~99.9% reduction reduction reduction reduction reduction

1000%

ALCS Internal Report LIQUID 16241 – MarkTen® XL Classic 3.5% nicotine, Official Stability Study – PMT1, 3, 6 and 9 months. Average of 140 intense puffs (55mL, 5 second duration, 30 second inter-puff interval).

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 14 ALCS Framework for Reduced Harm Tobacco Products

Constituent Risk Reduction Harm Reduction Reduction Individual Population

The Product Exposure and Health Risk Impact on the Population

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final15 | 15 Toxicology Reduced Risk Assessment: and Risk Pre-Clinical Studies Assessment

Toxicological literature review Ingredients risk assessment Flavors and carriers are: . Generally recognized as safe (GRAS) for use in foods . Food or pharmaceutical grade Carrier assessment 90 day in-vivo studies Flavor assessment

In-vitro toxicology studies E-liquid and aerosol condensate . OECD guidelines . Cytotoxicity and genotoxicity

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 16 ® No Cytotoxicity Observed from MarkTen Toxicology and Risk Aerosol Condensates in Neutral Red Uptake Assessment Assays1

8 MarkTen® Variants

Reference Cigarette 3R4F

• The 3R4F condensate: Positive response(IC50 of 0.048 ±0.004 mg/mL TPM) • E‐vapor condensates: Viability > 80% (IC50 could not be estimated) 1 Data shared at Society of Toxicology 2018 Annual Meeting. Doshi et al., Comparison of in vitro Cytotoxicity and Genotoxicity of Condensates Derived from E‐vapor Products and Combustible Cigarettes.

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 17 Toxicology and Risk No Mutagenicity Response Observed from Assessment MarkTen® Aerosol Condensates in Ames Test1

Ames Assay - TA98 +S9

Reference Cigarette 3R4F

8 MarkTen® Variants

1 Data shared at Society of Toxicology 2018 Annual Meeting. Doshi et al., Comparison of in vitro Cytotoxicity and Genotoxicity of Condensates Derived from E‐vapor Products and Combustible Cigarettes.

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 18 Toxicology Reduced Risk Assessment: and Risk Pre-Clinical Studies Assessment

Key Takeaways:

Ingredients risk assessment

No treatment related effects Carrier assessment . Survival Flavor assessment . Body weight . Clinical observations & chemistry parameters . Histopathology

E-liquid and aerosol condensate No evidence of mutagenicity or cytotoxicity

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 19 ALCS Framework for Reduced Harm Tobacco Products

Constituent Risk Reduction Harm Reduction Reduction Individual Population

The Product Exposure and Health Risk Impact on the Population

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final20 | 20 ® Studies in Adult MarkTen Users Have Lower Levels of Human Subjects Biomarkers of Exposure and Potential Harm

Pharmacokinetics/ Pharmacodynamics Nicotine delivery and satisfaction

Reduced Exposure 3-months Exposure reduction assessment (in progress)

Reduced Risk 6-months Biomarkers of potential harm (in progress)

Cross-sectional category study Exposure and risk assessment

Second hand vapor Impact on non-users

Results have been shared at the Global Forum on Nicotine, Society for Research on Nicotine and Tobacco, Tobacco Science Research Conference and other scientific meetings. Abstracts and presentations of these data can be found on our science website www.altria.com/alcs-science.

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 21 ® Studies in Adult MarkTen Nicotine Pharmacokinetic Studies Human Subjects Demonstrate a Range of Nicotine Deliveries1

4 Cigarette 2 MarkTen® (3 products)

Plasma Nicotine Concentration Plasma Nicotine Concentration (ng/mL) Nicotine Gum (4mg) 0 0 20406080100120140160180 Minutes

ALCS | Regulatory Affairs | 10/11/17 | DRAFT | Highly 1 Data shared at SocietyConfidential for Research on Nicotine | and Tobacco 2018 Annual Meeting. Oliveri et al., Characterization of Nicotine Exposure Profiles and Subjective Measures of e‐Vapor Products in Adult Smokers Relative to Conventional Cigarettes.

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 22 Studies in Adult Significant Differences in BOE and BOPH Human Subjects Between E-vapor Users and Cigarette Smokers1

120% Biomarkers of Biomarkers of Potential Exposure (BoE) Harm (BoPH)

100% Cig. smoker exposure level ** ** ** 80% * ** * * ** *** *** *** *** EVPTotal sample 60% ** ** TankTank users CartridgeCartridge users 40% *** *** 20% *** * P < 0.05 ** P < 0.005 Percent of cigarette exposure Percent of cigarette *** P < 0.0005

0% NNAL (ng/g NE (mg/g 3-HPMA COHb (%) WBC HDL-C 11-dehydro 8-epi (ng/g sICAM Cr) Cr) (ug/g Cr) (x103/uL) (mg/dL) (ng/g Cr) Cr) (ng/mL)

1 Data shared at Society for Research on Nicotine and Tobacco 2018 Annual Meeting. Oliveri et al., Cross‐Sectional Study Comparing Biomarkers of Exposure to Select Harmful and Potentially Harmful Constituents and Biomarkers of Inflammation and Oxidative Stress Between Adult E‐vapor Users and Conventional Cigarette Smokers.

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 23 ® Studies in Adult Clinical Studies Support MarkTen Users Human Subjects Have Lower Levels of Biomarkers of Exposure and Potential Harm

Key Takeaways:

Pharmacokinetics/ MarkTen® portfolio offers a range of nicotine Pharmacodynamics deliveries

Reduced Exposure 3-months Reduced exposure and risk biomarker studies for MarkTen® are in progress Reduced Risk 6-months

Significant difference in biomarkers of exposure Cross-sectional category study and potential harm in exclusive users of e-vapor products compared to cigarette smokers

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 24 ALCS Framework for Reduced Harm Tobacco Products

Constituent Risk Reduction Harm Reduction Reduction Individual Population

The Product Exposure and Health Risk Impact on the Population

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 25 Perception Consumer Perception and and Behavior Behavioral Assessment Assessment

Perception and behavioral intentions Risk perceptions and likelihood of use

Actual use studies Use patterns, likelihood of switching

In market study Market data on use behavior, likelihood of initiation and quitting

Product instruction Ability to comprehend the instructions comprehension and assembly of the product

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 26 ® Perception Risk Perceptions of MarkTen E-vapor and Behavior Products Compared to Cigarettes Assessment

Risk perception of MarkTen® relative to smoking cigarettes: Based on participant exposure to MarkTen® promotional materials

100% 12% 8% 8% 6% 8% 10% 10% 18% 80% 28% 23% 27% 34% 43% 33% 60% % of Participants of % 40% 74% 67% 60% 64% 59% 58% 49% 20%

Adult smokers Adult smokers E-vapor users Former Never Legal age to Legal age to age 24 planning to quit not planning to quit (n=426) tobacco users tobacco users age 24 users Non-users (n=415) (n=423) (n=417) (n=425) (n=424) (n=410) MT ranked less risky than Cig MT ranked equally risky as Cig MT ranked more risky than Cig

Source: Perceptions and Behavioral Intentions Study for Products Currently Marketed as MarkTen® E-vapor (ALCS-CMI-16-13-EV)

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 27 Perception and Behavior Flavor Portfolio Maximizes Appeal of Assessment MarkTen® Products Among Adult Smokers and Vapers Which of the following Adult smokers Adult smokers NOT E-vapor users products are most planning to quit planning to quit (N = 426) appealing to you? (N = 415) (N = 423) (select up to 3)

MarkTen®Smooth Smooth Menthol Menthol 2.4%MarkTen® Smooth16% Menthol 2.4% MarkTen®13% Smooth Menthol 2.4% 18% MarkTen®Bold Menthol Bold Menthol 4.0%MarkTen® 14%Bold Menthol 4.0% MarkTen®16% Bold Menthol 4.0% 17% MarkTen®Smooth Smooth Classic Classic 2.5%MarkTen® Smooth13% Classic 2.5% MarkTen®15% Smooth Classic 2.5% 15% MarkTen®Smooth Smooth Cream Cream 2.4%MarkTen® Smooth12% Cream 2.4% MarkTen®10% Smooth Cream 2.4% 19% MentholMarkTen® Menthol 3.5% MarkTen®12% Menthol 3.5% MarkTen®14% Menthol 3.5% 14% ClassicMarkTen® Classic 3.5% MarkTen®11% Classic 3.5% 12%MarkTen® Classic 3.5% 13% MarkTen®Oasis Caribbean Oasis 2.5%MarkTen® Caribbean11% Oasis 2.5% MarkTen®11% Caribbean Oasis 2.5% 23% MarkTen®Winter Mint Winter Mint 3.5% MarkTen®11% Winter Mint 3.5% MarkTen®12% Winter Mint 3.5% 20% MarkTen®Fusion Summer Fusion 2.5%MarkTen® Summer11% Fusion 2.5% MarkTen®10% Summer Fusion 2.5% 19% MarkTen®Classic Bold Classic 4.0% MarkTen®10% Bold Classic 4.0% MarkTen®13% Bold Classic 4.0% 16% MarkTen®Blend Bourbon Blend 2.5%MarkTen®9% Bourbon Blend 2.5% MarkTen®11% Bourbon Blend 2.5% 14% MarkTen®Mardi Gras Mardi Gras 2.5% MarkTen®9% Mardi Gras 2.5% MarkTen®8% Mardi Gras 2.5% 14% MarkTen®Harvest Harvest Blend Blend 2.5%MarkTen®7% Harvest Blend 2.5% MarkTen®5% Harvest Blend 2.5% 6% MarkTen®Vineyard Vineyard Blend Blend 2.5%MarkTen®6% Vineyard Blend 2.5% MarkTen®4% Vineyard Blend 2.5% 12% None of theseNone are appealing toNone me of these are appealing29% to me None of these are26% appealing to me 9%

No statistical significance testing Not all participants rated a product as appealing

Source: Perceptions and Behavioral Intentions Study for Products Currently Marketed as MarkTen® E-vapor (ALCS-CMI-16-13-EV)

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 28 Perception Adult Non-tobacco Users Do Not Find and Behavior MarkTen® Flavors Appealing Assessment

Which of the following products are most Former users Never users LA-24 Non-users appealing to you? (N = 417) (N = 425) (N = 410) (select up to 3)

MarkTen®Smooth Menthol Smooth Menthol…MarkTen®8% Smooth Menthol 2.4% 5% MarkTen® Smooth… 5% MarkTen®Bold MentholBold Menthol 4.0% MarkTen®5% Bold Menthol 4.0% 2% MarkTen® Bold… 3% MarkTen®Smooth Classic Smooth Classic…MarkTen®5% Smooth Classic 2.5% 2% MarkTen® Smooth… 4% SmoothMarkTen® Cream Smooth Cream…MarkTen®6% Smooth Cream 2.4% 7% MarkTen® Smooth… 7% MarkTen®Menthol Menthol 3.5% 5%MarkTen® Menthol 3.5% 2% MarkTen® Menthol 3.5% 3% MarkTen®Classic Classic 3.5% 4%MarkTen® Classic 3.5% 2% MarkTen® Classic 3.5% 2% MarkTen®Oasis Caribbean Oasis…MarkTen®8% Caribbean Oasis 2.5% 3% MarkTen® Caribbean… 8% MarkTen®Winter Winter Mint Mint 3.5% MarkTen®4% Winter Mint 3.5% 3% MarkTen® Winter… 7% Fusion MarkTen®7% Summer Fusion 2.5% 4% 7% MarkTen®Classic Bold Classic 4.0% MarkTen®4% Bold Classic 4.0% 1% 2% MarkTen®Blend Bourbon Blend…MarkTen®6% Bourbon Blend 2.5% 2% MarkTen® Bourbon… 3% MarkTen®Mardi MardiGras Gras 2.5% MarkTen®5% Mardi Gras 2.5% 4% MarkTen® Mardi Gras… 3% MarkTen®Harvest Harvest Blend Blend 2.5% MarkTen®3% Harvest Blend 2.5% 3% MarkTen® Harvest… 3% MarkTen®Vineyard VineyardBlend Blend…MarkTen®5% Vineyard Blend 2.5% 1% MarkTen® Vineyard… 3% None ofNone these are appealing…None of these are appealing to63% me None of these81% are… 73%

No statistical significance testing Not all participants rated a product as appealing

Source: Perceptions and Behavioral Intentions Study for Products Currently Marketed as MarkTen® E-vapor (ALCS-CMI-16-13-EV)

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 29 Perception Flavor Varieties Play an and Behavior Important Role in Switching Assessment

Proportion of participants using one or more flavor varieties by cigarette consumption at Week 6 # Flavor Total Sample Switched Decreased No Change in varieties used (0 CPD*) CPD CPD n=526 n=208 n=257 n=61 1 1.8 0.5 2.7 0 2 7.1 4.8 7 14.8 3 11.2 10.1 10.9 9.8 4 19.3 18.8 19.1 18.0 5 13.0 10.6 16.3 8.2 6 12.9 14.9 10.9 19.7 7 or more 34.7 40.4 33.1 29.5 *CPD: Cigarettes per day Source: A Longitudinal Study to Assess the Actual Use Of E-Vapor Products Currently Marketed as MarkTen®: MarkTen® Actual Use Study (M10-AUS)

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 30 ® Perception Every Day MarkTen Users are More Likely and Behavior to be Exclusive Users1 Assessment

Current Every day Some days Users

E-cigarettes only 25% 42% 12%

E-cigarettes + 1 other tobacco product 45% 36% 52%

E-cigarettes + 2 or more other tobacco products 31% 22% 37%

1 Data shared at Society for Research on Nicotine and Tobacco 2018 Annual Meeting. Largo et al., USE PATTERNS ASSOCIATED WITH SWITCHING AND DUAL USE AMONG CURRENT CONSUMERS OF MARKTEN®XL E‐VAPOR PRODUCTS

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 31 Perception Larger Proportion of Switchers Report and Behavior Every Day MarkTen® Use1 Assessment

Switchers Dual Users (n=349) (n=1,465)

Some day users Every day users 26% Some day 32% Every day users users 68% 74%

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 32 Perception Beyond “satisfying nicotine cravings” and Behavior Reasons for MarkTen® Use Vary by Users1 Assessment

Switchers Dual Users Reasons (n=349) (n=1,465) To satisfy my nicotine cravings 81% 71% To help prevent relapse 63% 15% To not smell like smoke/not bother other people with smoke 60% 43% It might be less harmful than cigarettes/other tobacco products 58% 29% Enjoy the taste 53% 45% Has a flavor I like 46% 39% To help cut back or quit smoking/using other tobacco products 41% 65% It might be less harmful for other people around me 40% 30% More affordable than cigarettes/other tobacco products 37% 25% To use in places where I cannot/shouldn’t smoke 30% 61% So I would not have to quit using tobacco products altogether 26% 16% Advertising or promotion (e.g., magazine ad, sign in store, coupon) 23% 34% Interested in using this type/brand of e-cigarette 20% 24% Curiosity 9% 16% All other reasons 3% 2% Don’t know 1% 1%

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 33 Perception Consumer Perception and and Behavior Behavioral Assessment Assessment

Key Takeaways: Sizable portion of AS perceive MarkTen® as Perception and equally or more harmful than cigarettes behavioral intentions MarkTen® flavor portfolio appeals primarily to current tobacco users Actual use studies Flavor varieties are necessary to maximize switching

In market study In-market data indicate every day use is associated with exclusive use of e-vapor

Product instruction comprehension Product instructions are easily understood

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 34 ALCS Framework for Reduced Harm Tobacco Products

Constituent Risk Reduction Harm Reduction Reduction Individual Population

The Product Exposure and Health Risk Impact on the Population

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final35 | 35 1 Risks and Population Assessment Benefits to the Population

Population Modeling Projection of likely impact on the population

Base Case Modified Case

Never Never Tobacco Tobacco User User

Cigarette Cigarette Dual E-vapor Smoker Smoker User User

Former Former Former Former Cigarette Cigarette Dual E-vapor Smoker Smoker User User

Modified Case – Base Case = Estimated change as a result of Introduction of E-vapor Product

1 Data shared at Society for Research on Nicotine and Tobacco 2018 Annual Meeting. Muhammad‐Kah et al., Estimating the Potential Population Health Impact of Authorizing the Marketing of E‐cigarettes in the US.

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 36 Risks and Population Assessment Benefits to the Population

Post-Market Surveillance Passive and active monitoring the impact of the introduction of the new product into the market

Active Surveillance Passive Surveillance

Consumer Health

Consumer Behavior

Consumer Perception

Adverse Events

In-market Prospective Literature National Internet Call center Poison cross- observational reviews surveys and forum AEs center sectional studies studies (e.g. monitoring monitoring registration surveys PATH) (pending validation)

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 37 Overall Conclusions

. E-vapor products present an opportunity to reduce the harm from cigarette smoking . We have a rigorous process to develop and evaluate our e-vapor products to demonstrate harm reduction opportunity . To advance harm reduction

. Generate sound science

. Truthful and accurate communications about relative risk

. Reframe debate about nicotine

. Transparent and reasonable product pathways that foster innovation

Altria Client Services l Regulatory Affairs l 1st Scientific Summit on Tobacco Harm Reduction l June 8 2018 l Final | 38