Slide 1: 24-Week e-Vapor Switching Study: Biomarkers of Exposure and Potential Harm
An Open-label, Randomized, Parallel Group, Controlled Study to Evaluate Changes in Biomarkers of Cigarette Smoke Exposure and Biomarkers of Potential Harm in Adult Smokers Who Completely Switch to Using e- Vapor Products for 24 Weeks Jeff Edmiston, Douglas Oliveri, Qiwei Liang, Mohamadi Sarkar CORES
Slide 2: Primary Objective
Primary Objective Compare absolute changes in selected biomarkers from Baseline to End of Study between adult smokers who continue to smoke conventional cigarettes and adult smokers who have completely switched to the test e-vapor products for 24 weeks J. Edmiston| Regulatory Affairs | Altria Client
Slide 3: Study Products
Study Products Battery Assembly Cartridge Product Nicotine Nicotinea (% by weight) (mg/puff) Classic Bold 4.0 0.20 Menthol Bold 4.0 0.23 a Based on 5s puff duration, 50mL puff volume and 30s inter-puff-interval J. Edmiston| Regulatory Affairs | Altria Client Services | CORESTA Oct 7-10th 2019 3
Slide 4: 12 Week e-Vapor Switching Study
12 Week e-Vapor Switching Study J. Edmiston| Regulatory Affairs | Altria Client Services | CORESTA Oct 7-10th 2019 4
Slide 5: 24 Week e-Vapor Switching Study
24 Week e-Vapor Switching Study J. Edmiston| Regulatory Affairs | Altria Client Services | CORESTA Oct 7-10th 2019 5
Slide 6: Key Measurements
Key Measurements Biomarkers of Exposure (BOE) Biomarker Constituent FDA Classification Total NNAL NNK Carcinogen Reproductive or Carboxyhemoglobin (COHb) Carbon Monoxide Developmental Toxicant Reproductive or Nicotine Equivalents Nicotine Developmental Toxicant, (nicotine and 5 metabolites) Addictiv
Slide 7: 24 Week Study Subject: Demographics
24 Week Study Subject: Demographics Classic Bold Menthol Bold Control Overall Trait Category/Statistics (n=48) (n=50) (n=52) (n=150) Female 23 (48%) 26 (52%) 27 (52%) 76 (51%) Gender Male 25 (52%) 24 (48%) 25 (48%) 74 (49%) Other 1 (0%) 1 (2%) 0 (0%) 2 (2%) Race Black or African American 9 (19%) 5 (
Slide 8: 24 Week Study: Tobacco History
24 Week Study: Tobacco History Classic Bold Menthol Bold Control Overall n 48 50 52 150 Cigarettes per Day Mean 17.4 17.6 17.7 17.6 SD 4.95 4.20 5.65 4.95 Years Smoked Mean 21.7 25.9 26.5 24.7 SD 7.90 10.59 11.19 10.19 J. Edmiston| Regulatory Affairs | Altria Client Services | CORESTA Oct 7-10th 201
Slide 9: 24 Week Study: Product Use
24Week Study: Product Use Cigarettes per Day 30 Average Cartridges per Day Group Week 24 25 N 47 20 Classic Bold Mean 1.65 15 SD 0.93 10 N 50 Menthol Bold Mean 1.48 5 SD 0.78 0 Baseline Week 15 Week 18 Week 21 Week 24 -5 Arithmetic Means ±SD J. Edmiston| Regulatory Affairs | Altria Client Services |
Slide 10: 24 Week Study: Compliance
24 Week Study: Compliance eCO Category n (%) Group Week N ≤5 >5 - ≤8 >8 12 47 46 ( 98) 1 ( 2) 0 ( 0) 15 44 41 ( 93) 2 ( 5) 1 ( 2) Classic 18 41 38 ( 93) 2 ( 5) 1 ( 2) Bold 21 42 35 ( 83) 5 ( 12) 2 ( 5) 24 42 35 ( 83) 5 ( 12) 2 ( 5) 12 50 43 ( 86) 7 ( 14) 0 ( 0) 15 49 40 ( 82) 6 ( 12) 3 ( 6) Menthol
Slide 11: Biomarkers of Exposure
Biomarkers of Exposure 700 NNAL 700 600 600 500 500 400 400 ng/g Cr 300 300 200 200 100 100 0 0 Baseline Week 6 Week 12 Baseline Week 12 Week 18 Week 24 -100 -100 COHb 10 10 9 9 8 8 Percent saturation 7 7 6 6 5 5 4 4 3 3 2 2 1 1 0 0 Baseline Week 6 Week 12 Baseline Week 12 Week 18 Week 24 Arithmetic
Slide 12: Biomarkers of Exposure
Biomarkers of Exposure Nicotine Equivalents 27 27 22 22 17 17 mg/g Cr 12 12 7 7 2 2 Baseline Week 6 Week 12 Baseline Week 12 Week 18 Week 24 Arithmetic Means ±SD J. Edmiston| Regulatory Affairs | Altria Client Services | CORESTA Oct 7-10th 2019 12
Slide 13: Biomarkers of Potential Harm
Biomarkers of Potential Harm 10 WBC 10 9 9 8 Count (x 10^3/uL) 8 7 7 6 6 5 5 4 4 Baseline Week 6 Week 12 Baseline Week 12 Week 18 Week 24 375 sICAM-1 375 325 325 275 275 ng/ml 225 225 175 175 125 125 Baseline Week 6 Week 12 Baseline Week 12 Week 18 Week 24 Arithmetic Means ±SD J. Edmiston| Regulator
Slide 14: Biomarkers of Potential Harm
Biomarkers of Potential Harm 1600 Urine 11-DTX1600B2 1400 1400 1200 1200 1000 1000 800 800 ng/g Cr 600 600 400 400 200 200 0 0 Baseline Week 6 Week 12 Baseline Week 12 Week 18 Week 24 70 HDL-C 70 65 65 60 60 55 55 50 50 mg/dL 45 45 40 40 35 35 30 30 25 25 20 Baseline Week 6 Week 12 Baseline Week 12
Slide 15: Biomarkers of Potential Harm
Biomarkers of Potential Harm Urine 8-epi-PG F2α 800 800 700 700 600 600 500 500 ng/g Cr 400 400 300 300 200 200 100 100 0 0 Baseline Week 6 Week 12 Baseline Week 12 Week 18 Week 24 Arithmetic Means ±SD J. Edmiston| Regulatory Affairs | Altria Client Services | CORESTA Oct 7-10th 2019 15
Slide 16: 12 Week Study: Biomarkers of Potential Harm
12 Week Study: Biomarkers of Potential Harm Absolute Change from Baseline to 12 Weeks LS Means LS Mean Difference Biomarker Group Test (n) Control (n) (Test - Control) p-value^ Classic Bold -0.686 (110) 0.111 (128) -0.797 0.0002 Whole Blood WBC Menthol Bold -0.342 (119) 0.111 (128) -0.453 0.0639 Cou
Slide 17: 24 Week Study: Biomarkers of Potential Harm
24 Week Study: Biomarkers of Potential Harm Absolute Change From Baseline to Week 24 LS Means LS Mean Difference Biomarker Group Test (n) Control (n) p-value (Test - Control) WBC Classic Bold -0.90 (42) 0.24 (44) -1.14 <.0001 Count (x 10^3/uL) Menthol Bold -0.85 (47) 0.24 (44) -1.09 <.0001 Urine 11-
Slide 18: 12 Week Study: Spirometry (percent predicted)
12 Week Study: Spirometry (percent predicted) 110 FEV1 110 FVC 105 105 100 100 95 95 90 90 85 85 80 80 75 75 Baseline Week 12 Baseline Week 12 110 FEV1/FVC 105 100 95 90 85 80 75 Baseline Week 12 Arithmetic Means ±SD J. Edmiston| Regulatory Affairs | Altria Client Services | CORESTA Oct 7-10th 2019
Slide 19: 24 Week Study: Spirometry (percent predicted)
24 Week Study: Spirometry (percent predicted) FEV1 110 FVC 110 105 105 100 100 95 95 90 85 90 80 85 75 80 70 65 75 Baseline 12 weeks 18weeks 24weeks 1 Baseline 2 12 Week 3 18 Week 4 24 Week Baseline Week 12 Week 18 Week 24 110 FEV1/FVC 105 100 95 90 85 1 2 3 4 Baseline Week 12 Week 18 Week 24 Arithm
Slide 20: 24 Week Study: Spirometry (percent predicted)
24 Week Study: Spirometry (percent predicted) Absolute Change From Baseline to Week 24 LS Means LS Mean Pulmonary Function Difference Parameter Comparison Test(n) Control(n) (Test - Control) p-value Classic Bold -1.32 (36) -3.88 (39) 2.56 0.0648 Percent of Predicted FEV1 (%) Menthol Bold -0.48 (40)
Slide 21: Overall Summary
Overall Summary Subjects switching to MarkTen® products demonstrated: - High level of compliance with switching to MarkTen® - Significant reduction in BOE (NNAL & COHb) Nicotine exposure remained the same as for cigarettes - Favorable changes in BOPH WBC, Urine 11-DTX B2 and sICAM significantly
Slide 22: Conclusions
Conclusions Complete switching from cigarettes to MarkTen® reduces exposure to smoke constituents and may reduce the risks of smoking related diseases Flavor does not appear to have an impact on the BOEs or BOPHs A 12-week study with the currently available biomarkers along with exclusive use
Slide 23: Presentation available at: www.altria.com/alcs-science
Presentation available at: www.altria.com/alcs-science J. Edmiston| Regulatory Affairs | Altria Client Services | CORESTA Oct 7-10th 2019 23 This Photo by Unknown Author is licensed under CC BY-NC-ND