NicVAX; An Immunotherapy Aid to Smoking Cessation and Long Term Abstinence February 27, 2011 Raafat Fahim, Ph.D. President and CEO, Nabi Biopharmaceuticals

NicVAX; An Immunotherapy Aid to Smoking Cessation and Long Term AbstinenceFebruary 27, 2011

Raafat Fahim, Ph.D. President and CEO, Nabi BiopharmaceuticalsS h a p i n gt h e F u t u r e o fH E A L T H C A R E

Nabi Biopharmaceuticals Confidential and Proprietary

*NicVAX; Significant Unmet NeedSmoking Impact1.3 billion smokersCurrently, 44 million adult smokers in the U.S.>75% start smoking cigarettes before the age of 185.4 million deaths/year worldwideSmoking is responsible for 1 in 5 deaths in U.S. $193 billion in annual healthcare costs associated with smoking-related illness2$96 billion in direct healthcare costs2The ConsumerAverage former smoker makes 8 to 11 attempts to quit Only 35% of all smokers who try to quit by themselves are permanently successful on any given attempt

4


*Why do people fail to quit long-term?Addiction90%(-)-Cotinine0.63.1()-Nornicotine0.20.4(-)-Nicotine-N-Oxide0.62.0(-)-Nicotine-N-Oxide0.01

NicVAX

Preclinical Studies and Theoretical Mechanism of Action (Clinical relevance unknown)S h a p i n gt h e F u t u r e o fH E A L T H C A R E


*Animals Actively Immunized with NicVAX Demonstrate Sequestering of Nicotine within the Bloodstream

1 Minute after Nicotine 0.1 mg/kg i.v. (~ 6-7 cigs)Satoskar, S. et al, Int Immunopharmacol 2003;3:957


*Pentel et al SRNT 2005 Nicotine Half-Life is Significantly Extended in Vaccinated Animals

NicVAX vaccinated individuals may experience attenuated withdrawal symptoms due to the increased nicotine half-life (t1/2) from hours to days


*In Animal Models, NicVAX Demonstrated Consistent Efficacy Antibodies to NicVAX Neutralized the pharmacological effects of nicotine onblood pressure1locomotor activity2nicotine discrimination3diminishes NSA4Prevented drug dependence and addiction when administered prophylactically5Administration during nicotine exposure prevented onset of withdrawal symptoms in animals6

1Pharm Biochem Behav 2000;66:1912Bioorg Med Chem 2004;12:5633Life Sci 2002;70:27934LeSage et.al Psychopharmacology 20055Resp 2002;69(3):2476Pharm Biochem Behav 2001:68:87


*NicVAX Elicited Polyclonal Antibodies Display Monoclonal-like Specificity : > 90% Competitive Inhibition with a Single NicVAX mAbRabbitRatNicVAX Mc-431 (Competitor) against Polyclonal Antibodies (Primary) on 3AMNic-Coated Plates


*Monoclonal Nature also Observed in NicVAX Immunized Subjects


*Upon smoking; nicotine travels quickly to the brainUntreated Smokerillustrativeillustrative

Day 01 Month2 Month3 Month4 Month


*Effective number of cigarettes seen by the brain decreases with time, making it easier to quit Antibodies partially shield the brain from nicotinePath to Continuous Abstinence along with the Potential to Reduce Cravings and Withdrawalsillustrative


NicVAX Injections

gmc ab plot

0.0862778121

1.1728174996

3.893622101

8.293072456

7

8.5557570913

19.580057206

24.1973562089

24.5973593558

38.5

14

41.8

Chart1

0.0862778121

1.1728174996

3.893622101

8.293072456

7

8.5557570913

19.580057206

24.1973562089

24.5973593558

38.5

14

41.8

63.6

65

Serology

SUBJIDTCDTCDTXTW0W4W5W6W7W8W9W10W12W13W14W16W17W20W26W27W30W40W52

0010032200 g/Sch10.070.180.170.31.822.111.7411.6612.179.77.824.9821.5619.6694.94

0010042200 g/Sch10.263.13.345.3513.0211.549.3625.9733.333422.5918.110.1532.3321.198.98

0010112200 g/Sch10.2611.5910.2528.6933.2128.2316.6541.258.849.435.634.96140.6183.898.284.8

0010212200 g/Sch10.230.350.370.82

0010232200 g/Sch10.240.340.641.722.795.052.65

0010242200 g/Sch10.170.350.340.993.142.6515.6723.8121.168.6610.2725.9433.7614.629.76

0010252200 g/Sch10.270.430.180.680.620.630.81.11.051.290.670.614.383.420.860.44

0020022200 g/Sch10.1117.712.7411.238.49

0020042200 g/Sch10.230.420.70.631.591.711.85.056.436.044.122.546.567.223.571.92

0020052200 g/Sch10.080.952.2110.5415.2414.4210.3236.1527.633.2717.4213.2333.4543.3717.6111.05

0020132200 g/Sch10.180.140.20.451.241.751.6412.112.98.245.412.115.367.934.783.55

0020152200 g/Sch10.060.420.893.14

0020202200 g/Sch10.135.4222.4148.9649.2147.7225.464.6

0020212200 g/Sch10.130.320.541.239.6712.2912.8236.6646.8742.436.3723.8256.242.631.8914.73

0020222200 g/Sch10.130.550.562.065.424.735.3716.0516.42138.825.1818.0815.546.442.93

0020252200 g/Sch10.081.181.342.597.48.098.1428.3149.639.8229.2620.0259.25020.8815.04

0020262200 g/Sch10.050.210.270.30.690.680.651.388.2718.967.064.1720.4241.7913.424.6

0020312200 g/Sch10.190.782.21

0020352200 g/Sch10.113.462.575.519.8616.3214.6128.6360.258.641.231.4377.25433.423.2

0040042200 g/Sch10.070.220.2732.361.96.246.526.042.882.2618.078.993.522.16

0050062200 g/Sch10.151.131.162.273.2533.296.399.7420.55178.631.854.7525.1112.62

0050092200 g/Sch10.080.210.240.580.761.31

0050132200 g/Sch10.052.432.813.158.216.448.1331.438.9128.9417.8222.8318.5914.917.65

0050172200 g/Sch10.050.380.553.998.6622.427.5353.31106.6185154.873.4123.4225.2196.4

0050182200 g/Sch10.050.340.533.6516.651126.863.0651.435.4581.642.9823.57

0050202200 g/Sch10.220.40.621.783.12

0050242200 g/Sch10.090.460.511.113.793.783.186.516.3912.048.573.376.828.523.761.67

0060032200 g/Sch10.0540.2240.2220.651.7961.8181.4567.5066.37610.727.425.2122.5619.369.716.22

0060072200 g/Sch10.050.1460.1740.2187.56811.5212.8414.0414.09815.42211.177.199.828.655.833.67

0060092200 g/Sch10.050.0640.060.0570.3420.3180.3162.4720.2084.9742.961.79.6510.263.851.84

0060162200 g/Sch10.050.2640.2720.3581.1180.790.7161.2517.21.411.681.224.476.83.842.11

0060252200 g/Sch10.1220.981.511.32613.614.850.0450.050.0539.463322.193339.9319.259.41

0060332200 g/Sch10.050.5340.5860.053.3825.0654.8010.08619.34625.3323.5312.9916.5528.2617.7310.09

0060352200 g/Sch10.0512.3861.9466.2913.0289.768.01817.0260.4325.2818.38

0060392200 g/Sch10.050.1680.1380.1740.2040.04519.8580.31712.2520.460.48

0060482200 g/Sch10.050.0860.0970.1121.2981.298

0060522200 g/Sch10.0480.8581.1824.6385.2264.4785.22418.8731.5132.9218.2419.7526.5535.1220.829.75

0070042200 g/Sch10.110.490.482.314.033.021.468.8521.1621.5411.533.0916.740.718.878.47

0080012200 g/Sch10.055.886.2919.41256284.6185.4205.4490357.8286.2112.4243.4360.4129.275.4

0080052200 g/Sch10.051.161.461.613.524.796.389.7410.589.055.068.922.8913.218.13

0080102200 g/Sch10.050.771.783.412.6710.423.8632.9714.644.8849.425.418.83

0080122200 g/Sch10.10.460.692.175.474.820.2221.3519.1417.312.1435.326.422.1510.41

0080142200 g/Sch10.210.540.951.635.715.718.997.7239.251.234.424.2731.146.23215.52

0080172200 g/Sch10.050.10.180.270.970.781.271.446.163.991.842.2824.448.612.31

0080202200 g/Sch10.11.540.9211.615.7313.769.5429.2930.2122.6213.278.1416.5718.428.454.49

0090052200 g/Sch10.122.072.154.7213.22

0090112200 g/Sch10.350.730.752.7413.9116.3323.0622.847.653.4565373.6106.27745.2

0090122200 g/Sch10.054.943.3610.4310.28

0090152200 g/Sch10.151.312.027.553.777.429.887.335.322.535.674.233.091.68

0090212200 g/Sch10.080.40.485.263.232.231.43

0010363200 g/Sch20.381.6713.8215.0510.189.119.389.418.116.9912.0324.3320.4123.8836.8316.520.06

0010403200 g/Sch20.050.230.691.181.382.212.342.151.941.712.062.291.781.741.460.970.55

0010533200 g/Sch20.392.594.7815.9926.2621.8120.7113.27

0010573200 g/Sch20.050.553.624.895.215.4412.4517.211.97.7621.0415.8721.0524.711.048.51

0020423200 g/Sch20.140.7111.5424.624.8442.842.644.0136.946.94

0030063200 g/Sch20.050.050.130.9910.784.72

0030203200 g/Sch20.080.8914.1586.649.68794.877.251.240.4936.843.9317.1841.7140.9111.977.73

0030393200 g/Sch20.1710.945.388.6215.3535.5424.367.32

0030413200 g/Sch20.252.445.158.9811.629.435.2327.245.9850.842.0947.297.436.521.91

0030443200 g/Sch20.050.7341.1516.624.329938.3133.4733.1552.64227.5839.9440.619.056.53

0030473200 g/Sch20.050.05

0030503200 g/Sch20.133.5992.687.849.847.7159.843.4122.2108.869188.8175.468.234.25

0030533200 g/Sch20.12.1511.8321.7716.1230.0733.1933.1529.3222.8247.2

0030573200 g/Sch23.8523.2517.232.4340.7243.4239.937.544440.438.615971.842.424.07

0040093200 g/Sch20.050.7612.911.8

0040113200 g/Sch20.090.714.759.525.9248.748.5628.8422.5410.3623.9423.5320.62

0040153200 g/Sch20.142.328.6116.0824.75

0040183200 g/Sch20.0818.0826.3946

0040213200 g/Sch20.21.32.7721.1624.6137.5748.6930.3430.2121.2665.860.645.82124.896.6118.631.13

0040263200 g/Sch20.162.333.473.155.176.1110.798.046.995.1410.3611.526.814.9813.836.94.35

0040283200 g/Sch20.10.941.562.064.574.518.9915.5915.3512.0624.3731.1821.450.44939.4525.03

0050433200 g/Sch20.292.8212.4920.5115.8

0050463200 g/Sch20.050.060.140.711.614.1616.3319.8614.77.9417.841.633.0481.494.639.821.71

0050473200 g/Sch20.082.177.434.4733.6240.8446.7546.8437.1935.013550.436.9571.26644.8526.22

0050483200 g/Sch20.130.651.191.861.73.938.368.937.255.629.214.639.51104.263.65

0050513200 g/Sch20.150.211.841.2410.17.787.99

0050543200 g/Sch20.081.481.6321.421.7341.446.253.246.3852.7645.656.444.234565.4930.6319.98

0060563200 g/Sch20.050.1460.694.625.619.9611.3315.910.59.39

0060603200 g/Sch20.05

0070083200 g/Sch20.110.290.650.710.821.321.521.16

0070143200 g/Sch20.132.2825.6124.424.6738.9431.9834.3627.5519.8817.6435.68

0070153200 g/Sch20.112.199.1115.4116.56

0070353200 g/Sch20.051.211.975.487.029.6216.2512.1710.389.13

0080183200 g/Sch20.110.731.170.880.691.251.371.241.180.941.171.180.641.261.170.750.39

0080233200 g/Sch20.274.7830.236.0129.1643.5159.693.883.678.1861.465.257.882.280.444.7719.02

0080283200 g/Sch20.080.692.227.6712.1938.2838.3836.6135.1234.1943.6224.636.9435.7924.8918.987.34

0080323200 g/Sch20.050.331.262.674.3911.3612.999.186.7243.5420.8614.8241.262511.924.79

0080333200 g/Sch20.051.416.1213.416.0131.0232.4628.9329.9537.9648.7932.6633.2350.427.7613.33

0090223200 g/Sch20.241.162.296.1417.5935.6921.422.629.9420.8929.1533.422.7413.39

0090303200 g/Sch20.060.967.879.1521.0431.5251.676.47370.283.8118.484.6128.4125.664.246.21

0090323200 g/Sch20.110.277.535.473.334.997.353.27

0090333200 g/Sch20.181.272.516.97.8422.2425.6922.3817.7818.0327.9641.3332.3782.876.644.3927.38

0090393200 g/Sch20.151.776.168.313.0420.783035.6828.3332.1448.2953.4350.2

0090403200 g/Sch20.050.393.76.755.737.5510.257.928.478.2914.8217.4613.3315.6923.9420.8312.39

0090413200 g/Sch20.051.9210.5510.6413.518.733.7631.232.131.829.843.535.5742.664.438.1918.76

0090433200 g/Sch20.350.380.560.751.274.185.258.215.322.648.1210.956.19

0090473200 g/Sch20.130.252.142.862.3916.081510.289.418.1713.4115.155.0818.5823.856.622.36

0090493200 g/Sch20.072.179.01

0090533200 g/Sch20.060.461.51

0090563200 g/Sch20.13

0010025400 g/Sch10.130.380.742.573.374.443.827.749.56.686.043.58.1511.467.526.04

0010075400 g/Sch10.116.15512281.871.254.49898.268.65038.0764.851.626.6414.78

0010095400 g/Sch10.163.814.626.1434.6527.436.4147.66057.644.239.8967.684.252.3821.44

0010155400 g/Sch10.20.610.974.177.977.424.2816.681624.0114.469.5241.8735.0616.657.73

0010265400 g/Sch10.11.491.354.24

0010275400 g/Sch10.051.282.645.2612.817.6311.329.633.1427.6214.0412.0145.3733.0613.126.25

0010335400 g/Sch10.111.218.7515.0115.244248.5330.1213.0941.1313.4110.32

0020035400 g/Sch10.10.380.8111.0936.5538.1432.3145.5844.2537.8331.9519.641.9940.6536.5925.77

0020105400 g/Sch10.212.553.667.8723.8621.823.8729.0442.475.648.439.6846.63151.811756

0020115400 g/Sch10.112.532.224.884.864.123.539.7212.3615.7213.715.5534.5640.8227.7922.76

0020235400 g/Sch10.161.181.522.062.372.832.4212.8410.6314.439.189.9557.441.1727.6114.6

0020275400 g/Sch10.220.871.18.8715.4514.4315.6342.9442.859.337.0430.5842.442.4432.66

0020345400 g/Sch10.070.740.784.687.026.294.9718.2431.6618.3613.797.3934.922.527.663.41

0020365400 g/Sch10.061.471.961.835.076.4710.7325.846.647.1630.4868.657.4

0020375400 g/Sch10.150.140.352.364.015.1223.168.5753.869.629.0917.11

0040035400 g/Sch10.1344.3315.1338.235.436.2111212203.4156.8139.4225.4243.4122.4132.6

0050055400 g/Sch10.180.330.454.15.134.433.4324.3327.722.515.959.7715.638.8518.110.16

0050075400 g/Sch10.20.470.666.114.483.642.889.7426.2621.638.165.7222.7924.36

0050155400 g/Sch10.073.663.394.879.4611.449.1518.1353.1643.62619.634.274.817.45

0050165400 g/Sch10.160.270.240.260.820.991.53.887.025.886.67.3427.4921.2110.554.13

0050225400 g/Sch10.050.120.130.1811.010.871.652.242.021.090.673.012.991.320.79

0050265400 g/Sch10.051.511.5417.7714.9913.779.422.3132.9925.0614.3327.31

0050275400 g/Sch10.072.762.345.468.077.187.1613.1519.6815.813.148.1515.0410.65.52

0050295400 g/Sch10.050.260.350.641.481.462.8820.9342.2133.0717.7347.7133.3818.498.92

0050305400 g/Sch10.050.10.270.320.881.271.512.233.533.92.92.272.681.670.99

0050315400 g/Sch10.050.370.6711.351.41.613.111.9822.3312.27.114.2412.874.56

0060015400 g/Sch10.050.8541.13.8085.4423.54810.9560.24610.8967.693.6611.9313.484.141.94

0060055400 g/Sch10.22619.34815.25616.57421.01824.89219.47615.846.210.0525.4416.6433.4764.631.5416.42

0060085400 g/Sch10.051.131.3581.5220.5815.12214.2821.08818.7521.78813.29.6328.3125.39.48.95

0060185400 g/Sch10.050.4840.61.9962.2142.172.043

0060295400 g/Sch10.056.82218.354206.8156.2121.481.6173.4139.6103.673.657.6148.4173.264.250.49

0060315400 g/Sch10.050.350.4060.6623.3624.6343.4760.1927.51618.3114.3224.2337.4422.8611.6

0060365400 g/Sch10.050.2560.239

0060385400 g/Sch10.050.2820.3120.3640.5570.730.0564.256

0060475400 g/Sch10.0651.4540.9866.14212.2411.3438.1618.80639.20630.9321.6113.8436.1446.9829.8917.37

0060515400 g/Sch12.8882.9588.87415.5180.1020.0515.99642.4338.1337.6314.863.2107.445.6431.62

0070025400 g/Sch10.110.380.381.282.434.073.297.0114.4411.229.0440.5

0070035400 g/Sch10.13.142.842.6511.3811.177.7436.152.8244.7326.7915.8696943.7626.58

0080035400 g/Sch10.051.822.853.956.887.347.8510.1413.8715.2314.416.3214.6629.0318.9714.75

0080045400 g/Sch10.180.240.370.491.711.762.143.194.253.632.714.3617.869.525.89

0080085400 g/Sch10.0528.5418.2921.2618.39.816.1721.5430.8823.615.2923.1137.22215.39

0080155400 g/Sch10.248.685.8340.834.443.3330.8873.284.86443.647.47104.486.248.848.5

0080165400 g/Sch10.110.580.641.362.192.512.2913.8113.5613.537.34.612.339.264.481.69

0080215400 g/Sch10.070.840.80.9812.8311.5610.552343.0435.8524.7415.7225.832.5923.6915.45

0090025400 g/Sch10.05

0090085400 g/Sch10.050.460.4910.4353.543016.54

0090095400 g/Sch10.056.839.9444.746466.652.28898.854

0090135400 g/Sch10.110.390.720.855.625.45.0722.7729.2621.4224.3819.090.7844.1137.4917.6

0090205400 g/Sch10.130.570.921.243.524.474.588.4513.8715.9813.929.9617.3626.2719.236.67

0090255400 g/Sch10.11.651.288.0320.41

0010316400 g/Sch20.312.874.2122.1916.841.1938.637.633.640.754.4403162.7858.7744.428.23

0010356400 g/Sch20.050.420.872.442.254.299.8914.6114.449.827.1624.4219.96

0010386400 g/Sch20.110.4214.8414.379.611.2225.3325.1125.3222.0625.625.5828.249.0352.3225.0714.95

0010396400 g/Sch20.051.392.87.397.4916.7214.4714.2212.61

0010496400 g/Sch20.11.889.5423.62

0020406400 g/Sch20.150.951.874.44

0020436400 g/Sch20.11

0030076400 g/Sch20.050.150.330.654.5110.28.6310.386.6413.6717.578.0424.7718.2611.385.83

0030116400 g/Sch20.050.714.076.34

0030136400 g/Sch20.173.7216.8659.6962.47871.445.450.3

0030176400 g/Sch20.057.3960.294.645131151175.4219163.6357.6395.8245.2539666.4224.676

0030226400 g/Sch20.074.87

0030236400 g/Sch20.161.161.935.535.1224.0421.524.1920.7417.1944.3828.2119.664239.5218.0416.75

0030296400 g/Sch20.051.783.422.237.098.525.193.852.5619.114.664.7610.0310.894.032.4

0030306400 g/Sch20.05

0030326400 g/Sch20.153.15.066.5420.9132.446.4537.1231.561.84635.685.4100.635.9334.35

0030386400 g/Sch20.361.322.2512.5936.5137.6136.9938.3634.9158.6144.6106172.6222137.498.6

0030496400 g/Sch20.050.613.163.314.5914.0113.319.0133.6119.111.9624.8721.469.036.85

0030586400 g/Sch20.051.342.161.851.434.384.243.172.72.039.376.473.712.4614.628.653.53

0040146400 g/Sch20.051.491.823.71418.4226.8928.7517.0114.6926.4441.2929.259.484.25237.48

0040196400 g/Sch20.122.8135.431.242.431.19

0040206400 g/Sch20.140.22

0040236400 g/Sch20.0548.3815.0830.2949.2245.487.290.473.2110121.486131.2140.64965.8

0050456400 g/Sch20.065.2510.2814.21227.5838.1638.2735.0629.8941.440.643.27397.868.828.64

0050506400 g/Sch20.050.927.213.7953.821.1687.4

0050526400 g/Sch20.150.531.123.884.0411.5116.616.82227.3536.7438.9627.6640.436.6523.5912.74

0050576400 g/Sch20.054.0114.3487.463.888.686.453.8

0060576400 g/Sch20.050.4013.2647.469.0925.5223.7818.1314.9510.9517.23

0070096400 g/Sch20.117.9841.447.4934.3552.4345.6531.3128.1933.4113.9430.113.627.4

0070106400 g/Sch20.120.411.724.853.024.3514.0416.213.9114.5441.6

0070186400 g/Sch20.12110.6615.69

0070216400 g/Sch20.140.731.783.933.5419.7530.7924.9915.5613.2439.436.2313.8640.1928.3210.185.27

0070276400 g/Sch20.070.792.8314.3410.8632.0456.885.434.870.45355.638.1918.87

0070336400 g/Sch20.111.397.276.6610.8313.8811.459.028.9512.5631.4819.088.87

0070346400 g/Sch20.050.871.063.282.35

0070366400 g/Sch20.151.4512.1716.1618.1136.583937.431.9425.7154.442.9225.860.647.421.7510.81

0070396400 g/Sch20.130.881.675.9815.130.61

0080246400 g/Sch20.080.361.8925.426.3230.3649.6345.243.1833.6139.7224.819.728.6831.3114.176.29

0080266400 g/Sch20.131.913.696.6112.594057.250.63778.489.6103.4134.8162.887.882.2

0080296400 g/Sch20.050.080.160.61.092.824.123.643.483.357.454.632.833.894.572.370.89

0080346400 g/Sch20.081.213.718.8511.0540.1375.4146.858.5845.545946.0425.6245.6848.1419.589.45

0090246400 g/Sch20.080.481.121.924.7413.3327.51

0090316400 g/Sch20.183.6955.2

0090366400 g/Sch20.0530.9436.8133.436.860.645.451.647.244.243.452.243.2765.273

0090386400 g/Sch20.140.876.074.564.015.916.826.814.895.290.2814.298.8113.7813.258.924.56

0090446400 g/Sch20.050.210.461.132.734.693.895.254.0617.1311.096.1510.9610.265.183.81

0090486400 g/Sch20.070.685.489.41

0090516400 g/Sch20.052.4823.2227.5823.439.846.250.21394343.4446.9721.4931.8642.3620.278.66

0090526400 g/Sch20.112.934.7911.7812.0632.635.1432.329.1823.3953.394926.58754.831.8518.08

0090546400 g/Sch20.150.584.495.125.9427.4436.9638.4624.1119.2444.0436.5322.1545.0350.8230.912.4

0090556400 g/Sch20.051.498.513.611.531.846.735.7633.7629.847.649.0220.7341.0731.5212.137.03

0010120Placebo/Sch10.080.110.120.150.110.120.170.140.20.170.130.070.10.340.310.12

0010130Placebo/Sch10.080.060.070.090.050.050.080.090.10.060.080.050.050.050.07

0010180Placebo/Sch10.180.10.110.050.170.10.090.180.160.140.10.370.10.850.080.1

0020010Placebo/Sch10.150.10.060.120.070.090.150.120.120.130.170.060.050.090.170.15

0020070Placebo/Sch10.110.110.060.050.080.080.120.10.140.090.050.060.090.130.180.11

0020090Placebo/Sch10.160.20.120.140.110.170.110.170.250.090.120.10.050.240.27

0020120Placebo/Sch10.050.050.050.05

0020140Placebo/Sch10.160.080.090.160.080.160.120.170.170.160.110.130.190.140.19

0020160Placebo/Sch10.070.050.070.080.090.110.110.120.050.120.110.050.050.050.210.06

0020190Placebo/Sch10.090.070.080.160.160.160.120.120.16

0020240Placebo/Sch10.070.050.050.080.070.080.090.060.090.160.090.050.120.050.140.06

0020290Placebo/Sch10.080.080.080.140.150.160.060.10.110.160.130.120.190.130.170.19

0020300Placebo/Sch10.050.060.110.130.160.120.170.070.130.120.10.140.510.520.470.31

0020330Placebo/Sch10.140.160.090.340.170.180.140.10.120.16

0020380Placebo/Sch10.060.050.050.130.10.050.110.120.120.170.060.050.050.110.1

0030020Placebo/Sch10.050.050.050.050.070.060.060.070.130.050.050.150.09

0030030Placebo/Sch10.170.130.2

0040010Placebo/Sch10.070.110.070.28

0040050Placebo/Sch10.050.050.090.180.050.080.320.060.060.060.070.140.050.160.090.05

0050010Placebo/Sch10.060.050.050.050.050.050.050.050.050.05

0050020Placebo/Sch10.120.110.060.050.060.050.050.070.050.10.060.30.090.110.090.1

0050080Placebo/Sch10.190.050.10.130.060.050.120.05

0050100Placebo/Sch10.050.050.090.080.050.050.10.050.050.050.070.20.210.050.080.21

0050140Placebo/Sch10.050.050.050.050.050.050.050.050.080.050.050.050.050.050.050.05

0050210Placebo/Sch10.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05

0050250Placebo/Sch10.050.090.070.050.110.050.080.070.150.140.160.150.090.43

0050280Placebo/Sch10.050.050.050.050.050.050.050.050.050.050.050.050.050.1

0050320Placebo/Sch10.090.050.080.050.110.1

0050330Placebo/Sch10.050.050.050.050.050.050.050.050.050.130.120.050.050.050.050.05

0050380Placebo/Sch10.230.070.20.180.210.050.40.090.080.110.180.190.11

0050390Placebo/Sch10.070.120.130.130.110.140.180.10.10.40.220.130.10.160.220.12

0050400Placebo/Sch10.050.140.050.060.080.110.080.090.120.120.140.120.090.190.130.13

0060100Placebo/Sch10.050.050.050.0590.050.050.050.050.050.050.190.120.080.090.380.17

0060110Placebo/Sch10.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05

0060120Placebo/Sch10.0510.0510.0480.1060.0680.0650.0470.0630.0520.0730.220.160.230.30.360.38

0060230Placebo/Sch10.050.050.050.050.050.050.050.050.050.090.070.050.120.360.10.06

0060410Placebo/Sch10.050.050.050.050.050.0538.770.050.090.090.070.05

0060440Placebo/Sch10.0530.0480.0550.0530.0670.0530.0560.0470.0530.10.060.060.050.280.110.11

0070010Placebo/Sch10.120.140.140.160.120.170.170.170.130.180.190.130.160.140.20.31

0080020Placebo/Sch10.070.110.080.220.210.560.160.120.130.140.320.360.380.20.170.39

0080060Placebo/Sch10.050.050.05

0080070Placebo/Sch10.050.050.080.050.050.050.050.080.060.050.050.060.050.090.120.14

0080090Placebo/Sch10.120.170.130.140.170.170.180.10.10.30.110.190.130.130.150.2

0080110Placebo/Sch10.060.050.420.050.050.060.150.050.050.050.05

0080130Placebo/Sch10.120.120.250.220.170.160.210.250.280.150.170.130.160.150.190.11

0090030Placebo/Sch10.110.090.050.050.09

0090040Placebo/Sch10.180.180.170.180.150.150.270.170.180.220.310.370.260.260.310.25

0090060Placebo/Sch10.050.050.050.050.050.050.050.050.070.060.050.050.050.050.060.05

0090140Placebo/Sch10.050.050.050.050.06

0090190Placebo/Sch10.050.050.050.060.05

0010411Placebo/Sch20.240.270.240.220.160.240.240.210.160.2536.870.210.210.270.30.180.15

0010421Placebo/Sch20.050.080.090.070.090.090.070.080.070.070.070.080.170.440.050.05

0010451Placebo/Sch20.130.050.050.050.050.170.050.050.050.050.050.050.050.260.090.05

0010461Placebo/Sch20.050.060.050.070.080.050.050.070.050.060.050.070.060.230.050.110.05

0010481Placebo/Sch20.120.050.060.060.060.090.140.050.080.060.050.060.050.260.050.069.64

0010561Placebo/Sch20.050.150.170.130.150.150.160.090.260.250.190.110.350.190.110.14

0010611Placebo/Sch20.10.110.10.080.090.080.080.090.090.080.070.070.060.110.050.06

0020411Placebo/Sch20.120.140.050.090.070.130.050.060.050.050.050.130.10.180.230.120.1

0020441Placebo/Sch20.140.260.260.280.250.340.210.250.260.160.210.220.190.250.230.270.15

0020501Placebo/Sch20.060.050.050.080.050.050.050.160.090.050.05

0030051Placebo/Sch20.050.050.050.050.060.050.070.070.070.070.050.050.050.050.050.05

0030181Placebo/Sch20.050.050.050.140.080.180.19

0030191Placebo/Sch20.090.050.050.070.050.150.050.120.1

0030241Placebo/Sch20.150.140.260.190.240.170.190.190.260.260.250.230.290.380.29

0030281Placebo/Sch20.060.13

0030311Placebo/Sch20.180.240.140.140.160.190.150.240.160.110.120.140.310.320.110.34

0030341Placebo/Sch20.110.140.090.050.120.110.10.10.10.130.150.130.110.120.10.53

0030351Placebo/Sch20.050.050.070.110.070.090.110.080.060.060.070.080.150.050.110.11

0030421Placebo/Sch20.050.050.050.060.050.050.110.050.3

0030431Placebo/Sch20.20.10.270.080.43

0030461Placebo/Sch20.10.160.110.180.190.160.120.130.13

0030521Placebo/Sch20.240.130.380.230.30.20.130.090.140.10.090.13

0030541Placebo/Sch20.190.150.090.120.180.110.260.140.110.10.240.170.080.130.190.20.12

0040071Placebo/Sch20.050.070.050.05

0040081Placebo/Sch20.280.30.280.30.340.450.281.480.250.270.340.390.410.350.35

0040121Placebo/Sch20.050.10.10.050.050.06

0040171Placebo/Sch20.050.050.050.050.050.050.050.050.050.050.050.050.060.050.130.050.05

0040241Placebo/Sch20.170.20.140.250.090.270.130.10.190.240.370.150.40.260.280.2

0040271Placebo/Sch20.110.120.270.130.140.180.120.110.160.110.220.110.120.340.290.30.18

0050411Placebo/Sch20.080.240.130.140.170.160.150.130.120.320.260.350.180.450.310.220.21

0070131Placebo/Sch20.050.050.050.050.050.050.050.050.050.090.170.050.05

0070161Placebo/Sch20.050.050.050.050.05

0070171Placebo/Sch20.140.210.310.320.190.240.170.17

0070191Placebo/Sch20.060.050.050.050.050.050.050.050.050.050.070.050.050.05

0070251Placebo/Sch20.120.130.090.150.10.120.110.140.120.060.070.060.080.150.140.11

0070291Placebo/Sch20.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05

0070301Placebo/Sch20.160.110.13

0070311Placebo/Sch20.20.140.20.130.110.140.19

0070321Placebo/Sch20.130.10.120.10.110.160.080.10.10.090.110.190.20.160.120.170.06

0070371Placebo/Sch20.170.330.290.150.20.160.270.230.24

0080191Placebo/Sch20.230.370.270.230.140.210.230.170.240.250.130.270.150.160.210.220.15

0080221Placebo/Sch20.190.30.180.20.20.220.290.130.190.110.150.160.230.290.330.350.2

0080251Placebo/Sch20.080.180.090.090.220.16

0080271Placebo/Sch20.060.070.220.120.230.230.180.060.10.140.070.270.10.130.15

0080311Placebo/Sch20.130.210.170.130.130.120.190.120.110.160.140.120.20.110.10.09

0090231Placebo/Sch20.110.090.120.130.10.080.110.20.180.350.314.680.20.070.260.260.17

0090261Placebo/Sch20.060.060.10.080.070.140.260.110.110.190.160.080.140.080.150.150.13

0090281Placebo/Sch20.160.10.130.140.160.140.250.150.190.30.310.210.150.210.240.260.13

0090421Placebo/Sch20.120.20.180.180.260.160.150.160.330.190.190.170.280.120.150.190.1

0090461Placebo/Sch20.060.110.120.110.170.050.090.120.190.120.060.060.120.110.120.110.08


045678910121314161720222326273036404852

200 g/Schedule 10.09483597560.66795890810.77350342121.7709381794.50471063854.96216546824.32102556537.340143157912.324534427318.053931982213.475375668.78012911818.552334095227.527913161414.2441565067.1256674902

400 g/Schedule 10.08867859291.03636037471.25720722983.79809748627.75681841847.02724284465.752595064915.831948778924.490154644320.647275303717.556768619712.41455344829.61403354134.885670471519.540453356911.1913651892

200 g/Schedule 20.10196497480.90350480683.97681135687.33796758737.981926135114.92823233519.1907395618.788545830118.840338454315.558696697123.128860829725.614652564618.14956192731.498606247432.536040115118.40647120088.4258287124

5 Injections 400 g0.08627781211.17281749963.8936221018.2930724568.555757091319.58005720624.197356208924.597359355820.941241757218.83226130432.708986806936.003218939922.617873966944.403241952543.677727648521.550236473912.2981834995

6 Injections 400 g (est.)0.08627781211.17281749963.8936221018.2930724568.555757091319.58005720624.197356208924.597359355838.541.863.66546.768.567.845.636.4


*Supportive CounselingAntibodies partially shield the brain from nicotine Easier to Quit Smoking Target Quit DateSuccessful Quit illustrative Brain exposure to nicotine was reduced gradually with the rise of antibodies Bound/free nicotine equilibrium results in continuous low levels of free nicotine Antibodies persistence for months Aligned quit date and counseling with high antibodies Path to Continuous Abstinence along with the Potential to Reduce Cravings and Withdrawals


NicVAX Injections

gmc ab plot

0.0862778121

1.1728174996

3.893622101

8.293072456

7

8.5557570913

19.580057206

24.1973562089

24.5973593558

38.5

14

41.8

Chart1

0.0862778121

1.1728174996

3.893622101

8.293072456

7

8.5557570913

19.580057206

24.1973562089

24.5973593558

38.5

14

41.8

63.6

65

Serology


0010032200 g/Sch10.070.180.170.31.822.111.7411.6612.179.77.824.9821.5619.6694.94

0010042200 g/Sch10.263.13.345.3513.0211.549.3625.9733.333422.5918.110.1532.3321.198.98

0010112200 g/Sch10.2611.5910.2528.6933.2128.2316.6541.258.849.435.634.96140.6183.898.284.8

0010212200 g/Sch10.230.350.370.82

0010232200 g/Sch10.240.340.641.722.795.052.65

0010242200 g/Sch10.170.350.340.993.142.6515.6723.8121.168.6610.2725.9433.7614.629.76

0010252200 g/Sch10.270.430.180.680.620.630.81.11.051.290.670.614.383.420.860.44

0020022200 g/Sch10.1117.712.7411.238.49

0020042200 g/Sch10.230.420.70.631.591.711.85.056.436.044.122.546.567.223.571.92

0020052200 g/Sch10.080.952.2110.5415.2414.4210.3236.1527.633.2717.4213.2333.4543.3717.6111.05

0020132200 g/Sch10.180.140.20.451.241.751.6412.112.98.245.412.115.367.934.783.55

0020152200 g/Sch10.060.420.893.14

0020202200 g/Sch10.135.4222.4148.9649.2147.7225.464.6

0020212200 g/Sch10.130.320.541.239.6712.2912.8236.6646.8742.436.3723.8256.242.631.8914.73

0020222200 g/Sch10.130.550.562.065.424.735.3716.0516.42138.825.1818.0815.546.442.93

0020252200 g/Sch10.081.181.342.597.48.098.1428.3149.639.8229.2620.0259.25020.8815.04

0020262200 g/Sch10.050.210.270.30.690.680.651.388.2718.967.064.1720.4241.7913.424.6

0020312200 g/Sch10.190.782.21

0020352200 g/Sch10.113.462.575.519.8616.3214.6128.6360.258.641.231.4377.25433.423.2

0040042200 g/Sch10.070.220.2732.361.96.246.526.042.882.2618.078.993.522.16

0050062200 g/Sch10.151.131.162.273.2533.296.399.7420.55178.631.854.7525.1112.62

0050092200 g/Sch10.080.210.240.580.761.31

0050132200 g/Sch10.052.432.813.158.216.448.1331.438.9128.9417.8222.8318.5914.917.65

0050172200 g/Sch10.050.380.553.998.6622.427.5353.31106.6185154.873.4123.4225.2196.4

0050182200 g/Sch10.050.340.533.6516.651126.863.0651.435.4581.642.9823.57

0050202200 g/Sch10.220.40.621.783.12

0050242200 g/Sch10.090.460.511.113.793.783.186.516.3912.048.573.376.828.523.761.67

0060032200 g/Sch10.0540.2240.2220.651.7961.8181.4567.5066.37610.727.425.2122.5619.369.716.22

0060072200 g/Sch10.050.1460.1740.2187.56811.5212.8414.0414.09815.42211.177.199.828.655.833.67

0060092200 g/Sch10.050.0640.060.0570.3420.3180.3162.4720.2084.9742.961.79.6510.263.851.84

0060162200 g/Sch10.050.2640.2720.3581.1180.790.7161.2517.21.411.681.224.476.83.842.11

0060252200 g/Sch10.1220.981.511.32613.614.850.0450.050.0539.463322.193339.9319.259.41

0060332200 g/Sch10.050.5340.5860.053.3825.0654.8010.08619.34625.3323.5312.9916.5528.2617.7310.09

0060352200 g/Sch10.0512.3861.9466.2913.0289.768.01817.0260.4325.2818.38

0060392200 g/Sch10.050.1680.1380.1740.2040.04519.8580.31712.2520.460.48

0060482200 g/Sch10.050.0860.0970.1121.2981.298

0060522200 g/Sch10.0480.8581.1824.6385.2264.4785.22418.8731.5132.9218.2419.7526.5535.1220.829.75

0070042200 g/Sch10.110.490.482.314.033.021.468.8521.1621.5411.533.0916.740.718.878.47

0080012200 g/Sch10.055.886.2919.41256284.6185.4205.4490357.8286.2112.4243.4360.4129.275.4

0080052200 g/Sch10.051.161.461.613.524.796.389.7410.589.055.068.922.8913.218.13

0080102200 g/Sch10.050.771.783.412.6710.423.8632.9714.644.8849.425.418.83

0080122200 g/Sch10.10.460.692.175.474.820.2221.3519.1417.312.1435.326.422.1510.41

0080142200 g/Sch10.210.540.951.635.715.718.997.7239.251.234.424.2731.146.23215.52

0080172200 g/Sch10.050.10.180.270.970.781.271.446.163.991.842.2824.448.612.31

0080202200 g/Sch10.11.540.9211.615.7313.769.5429.2930.2122.6213.278.1416.5718.428.454.49

0090052200 g/Sch10.122.072.154.7213.22

0090112200 g/Sch10.350.730.752.7413.9116.3323.0622.847.653.4565373.6106.27745.2

0090122200 g/Sch10.054.943.3610.4310.28

0090152200 g/Sch10.151.312.027.553.777.429.887.335.322.535.674.233.091.68

0090212200 g/Sch10.080.40.485.263.232.231.43

0010363200 g/Sch20.381.6713.8215.0510.189.119.389.418.116.9912.0324.3320.4123.8836.8316.520.06

0010403200 g/Sch20.050.230.691.181.382.212.342.151.941.712.062.291.781.741.460.970.55

0010533200 g/Sch20.392.594.7815.9926.2621.8120.7113.27

0010573200 g/Sch20.050.553.624.895.215.4412.4517.211.97.7621.0415.8721.0524.711.048.51

0020423200 g/Sch20.140.7111.5424.624.8442.842.644.0136.946.94

0030063200 g/Sch20.050.050.130.9910.784.72

0030203200 g/Sch20.080.8914.1586.649.68794.877.251.240.4936.843.9317.1841.7140.9111.977.73

0030393200 g/Sch20.1710.945.388.6215.3535.5424.367.32

0030413200 g/Sch20.252.445.158.9811.629.435.2327.245.9850.842.0947.297.436.521.91

0030443200 g/Sch20.050.7341.1516.624.329938.3133.4733.1552.64227.5839.9440.619.056.53

0030473200 g/Sch20.050.05

0030503200 g/Sch20.133.5992.687.849.847.7159.843.4122.2108.869188.8175.468.234.25

0030533200 g/Sch20.12.1511.8321.7716.1230.0733.1933.1529.3222.8247.2

0030573200 g/Sch23.8523.2517.232.4340.7243.4239.937.544440.438.615971.842.424.07

0040093200 g/Sch20.050.7612.911.8

0040113200 g/Sch20.090.714.759.525.9248.748.5628.8422.5410.3623.9423.5320.62

0040153200 g/Sch20.142.328.6116.0824.75

0040183200 g/Sch20.0818.0826.3946

0040213200 g/Sch20.21.32.7721.1624.6137.5748.6930.3430.2121.2665.860.645.82124.896.6118.631.13

0040263200 g/Sch20.162.333.473.155.176.1110.798.046.995.1410.3611.526.814.9813.836.94.35

0040283200 g/Sch20.10.941.562.064.574.518.9915.5915.3512.0624.3731.1821.450.44939.4525.03

0050433200 g/Sch20.292.8212.4920.5115.8

0050463200 g/Sch20.050.060.140.711.614.1616.3319.8614.77.9417.841.633.0481.494.639.821.71

0050473200 g/Sch20.082.177.434.4733.6240.8446.7546.8437.1935.013550.436.9571.26644.8526.22

0050483200 g/Sch20.130.651.191.861.73.938.368.937.255.629.214.639.51104.263.65

0050513200 g/Sch20.150.211.841.2410.17.787.99

0050543200 g/Sch20.081.481.6321.421.7341.446.253.246.3852.7645.656.444.234565.4930.6319.98

0060563200 g/Sch20.050.1460.694.625.619.9611.3315.910.59.39

0060603200 g/Sch20.05

0070083200 g/Sch20.110.290.650.710.821.321.521.16

0070143200 g/Sch20.132.2825.6124.424.6738.9431.9834.3627.5519.8817.6435.68

0070153200 g/Sch20.112.199.1115.4116.56

0070353200 g/Sch20.051.211.975.487.029.6216.2512.1710.389.13

0080183200 g/Sch20.110.731.170.880.691.251.371.241.180.941.171.180.641.261.170.750.39

0080233200 g/Sch20.274.7830.236.0129.1643.5159.693.883.678.1861.465.257.882.280.444.7719.02

0080283200 g/Sch20.080.692.227.6712.1938.2838.3836.6135.1234.1943.6224.636.9435.7924.8918.987.34

0080323200 g/Sch20.050.331.262.674.3911.3612.999.186.7243.5420.8614.8241.262511.924.79

0080333200 g/Sch20.051.416.1213.416.0131.0232.4628.9329.9537.9648.7932.6633.2350.427.7613.33

0090223200 g/Sch20.241.162.296.1417.5935.6921.422.629.9420.8929.1533.422.7413.39

0090303200 g/Sch20.060.967.879.1521.0431.5251.676.47370.283.8118.484.6128.4125.664.246.21

0090323200 g/Sch20.110.277.535.473.334.997.353.27

0090333200 g/Sch20.181.272.516.97.8422.2425.6922.3817.7818.0327.9641.3332.3782.876.644.3927.38

0090393200 g/Sch20.151.776.168.313.0420.783035.6828.3332.1448.2953.4350.2

0090403200 g/Sch20.050.393.76.755.737.5510.257.928.478.2914.8217.4613.3315.6923.9420.8312.39

0090413200 g/Sch20.051.9210.5510.6413.518.733.7631.232.131.829.843.535.5742.664.438.1918.76

0090433200 g/Sch20.350.380.560.751.274.185.258.215.322.648.1210.956.19

0090473200 g/Sch20.130.252.142.862.3916.081510.289.418.1713.4115.155.0818.5823.856.622.36

0090493200 g/Sch20.072.179.01

0090533200 g/Sch20.060.461.51

0090563200 g/Sch20.13

0010025400 g/Sch10.130.380.742.573.374.443.827.749.56.686.043.58.1511.467.526.04

0010075400 g/Sch10.116.15512281.871.254.49898.268.65038.0764.851.626.6414.78

0010095400 g/Sch10.163.814.626.1434.6527.436.4147.66057.644.239.8967.684.252.3821.44

0010155400 g/Sch10.20.610.974.177.977.424.2816.681624.0114.469.5241.8735.0616.657.73

0010265400 g/Sch10.11.491.354.24

0010275400 g/Sch10.051.282.645.2612.817.6311.329.633.1427.6214.0412.0145.3733.0613.126.25

0010335400 g/Sch10.111.218.7515.0115.244248.5330.1213.0941.1313.4110.32

0020035400 g/Sch10.10.380.8111.0936.5538.1432.3145.5844.2537.8331.9519.641.9940.6536.5925.77

0020105400 g/Sch10.212.553.667.8723.8621.823.8729.0442.475.648.439.6846.63151.811756

0020115400 g/Sch10.112.532.224.884.864.123.539.7212.3615.7213.715.5534.5640.8227.7922.76

0020235400 g/Sch10.161.181.522.062.372.832.4212.8410.6314.439.189.9557.441.1727.6114.6

0020275400 g/Sch10.220.871.18.8715.4514.4315.6342.9442.859.337.0430.5842.442.4432.66

0020345400 g/Sch10.070.740.784.687.026.294.9718.2431.6618.3613.797.3934.922.527.663.41

0020365400 g/Sch10.061.471.961.835.076.4710.7325.846.647.1630.4868.657.4

0020375400 g/Sch10.150.140.352.364.015.1223.168.5753.869.629.0917.11

0040035400 g/Sch10.1344.3315.1338.235.436.2111212203.4156.8139.4225.4243.4122.4132.6

0050055400 g/Sch10.180.330.454.15.134.433.4324.3327.722.515.959.7715.638.8518.110.16

0050075400 g/Sch10.20.470.666.114.483.642.889.7426.2621.638.165.7222.7924.36

0050155400 g/Sch10.073.663.394.879.4611.449.1518.1353.1643.62619.634.274.817.45

0050165400 g/Sch10.160.270.240.260.820.991.53.887.025.886.67.3427.4921.2110.554.13

0050225400 g/Sch10.050.120.130.1811.010.871.652.242.021.090.673.012.991.320.79

0050265400 g/Sch10.051.511.5417.7714.9913.779.422.3132.9925.0614.3327.31

0050275400 g/Sch10.072.762.345.468.077.187.1613.1519.6815.813.148.1515.0410.65.52

0050295400 g/Sch10.050.260.350.641.481.462.8820.9342.2133.0717.7347.7133.3818.498.92

0050305400 g/Sch10.050.10.270.320.881.271.512.233.533.92.92.272.681.670.99

0050315400 g/Sch10.050.370.6711.351.41.613.111.9822.3312.27.114.2412.874.56

0060015400 g/Sch10.050.8541.13.8085.4423.54810.9560.24610.8967.693.6611.9313.484.141.94

0060055400 g/Sch10.22619.34815.25616.57421.01824.89219.47615.846.210.0525.4416.6433.4764.631.5416.42

0060085400 g/Sch10.051.131.3581.5220.5815.12214.2821.08818.7521.78813.29.6328.3125.39.48.95

0060185400 g/Sch10.050.4840.61.9962.2142.172.043

0060295400 g/Sch10.056.82218.354206.8156.2121.481.6173.4139.6103.673.657.6148.4173.264.250.49

0060315400 g/Sch10.050.350.4060.6623.3624.6343.4760.1927.51618.3114.3224.2337.4422.8611.6

0060365400 g/Sch10.050.2560.239

0060385400 g/Sch10.050.2820.3120.3640.5570.730.0564.256

0060475400 g/Sch10.0651.4540.9866.14212.2411.3438.1618.80639.20630.9321.6113.8436.1446.9829.8917.37

0060515400 g/Sch12.8882.9588.87415.5180.1020.0515.99642.4338.1337.6314.863.2107.445.6431.62

0070025400 g/Sch10.110.380.381.282.434.073.297.0114.4411.229.0440.5

0070035400 g/Sch10.13.142.842.6511.3811.177.7436.152.8244.7326.7915.8696943.7626.58

0080035400 g/Sch10.051.822.853.956.887.347.8510.1413.8715.2314.416.3214.6629.0318.9714.75

0080045400 g/Sch10.180.240.370.491.711.762.143.194.253.632.714.3617.869.525.89

0080085400 g/Sch10.0528.5418.2921.2618.39.816.1721.5430.8823.615.2923.1137.22215.39

0080155400 g/Sch10.248.685.8340.834.443.3330.8873.284.86443.647.47104.486.248.848.5

0080165400 g/Sch10.110.580.641.362.192.512.2913.8113.5613.537.34.612.339.264.481.69

0080215400 g/Sch10.070.840.80.9812.8311.5610.552343.0435.8524.7415.7225.832.5923.6915.45

0090025400 g/Sch10.05

0090085400 g/Sch10.050.460.4910.4353.543016.54

0090095400 g/Sch10.056.839.9444.746466.652.28898.854

0090135400 g/Sch10.110.390.720.855.625.45.0722.7729.2621.4224.3819.090.7844.1137.4917.6

0090205400 g/Sch10.130.570.921.243.524.474.588.4513.8715.9813.929.9617.3626.2719.236.67

0090255400 g/Sch10.11.651.288.0320.41

0010316400 g/Sch20.312.874.2122.1916.841.1938.637.633.640.754.4403162.7858.7744.428.23

0010356400 g/Sch20.050.420.872.442.254.299.8914.6114.449.827.1624.4219.96

0010386400 g/Sch20.110.4214.8414.379.611.2225.3325.1125.3222.0625.625.5828.249.0352.3225.0714.95

0010396400 g/Sch20.051.392.87.397.4916.7214.4714.2212.61

0010496400 g/Sch20.11.889.5423.62

0020406400 g/Sch20.150.951.874.44

0020436400 g/Sch20.11

0030076400 g/Sch20.050.150.330.654.5110.28.6310.386.6413.6717.578.0424.7718.2611.385.83

0030116400 g/Sch20.050.714.076.34

0030136400 g/Sch20.173.7216.8659.6962.47871.445.450.3

0030176400 g/Sch20.057.3960.294.645131151175.4219163.6357.6395.8245.2539666.4224.676

0030226400 g/Sch20.074.87

0030236400 g/Sch20.161.161.935.535.1224.0421.524.1920.7417.1944.3828.2119.664239.5218.0416.75

0030296400 g/Sch20.051.783.422.237.098.525.193.852.5619.114.664.7610.0310.894.032.4

0030306400 g/Sch20.05

0030326400 g/Sch20.153.15.066.5420.9132.446.4537.1231.561.84635.685.4100.635.9334.35

0030386400 g/Sch20.361.322.2512.5936.5137.6136.9938.3634.9158.6144.6106172.6222137.498.6

0030496400 g/Sch20.050.613.163.314.5914.0113.319.0133.6119.111.9624.8721.469.036.85

0030586400 g/Sch20.051.342.161.851.434.384.243.172.72.039.376.473.712.4614.628.653.53

0040146400 g/Sch20.051.491.823.71418.4226.8928.7517.0114.6926.4441.2929.259.484.25237.48

0040196400 g/Sch20.122.8135.431.242.431.19

0040206400 g/Sch20.140.22

0040236400 g/Sch20.0548.3815.0830.2949.2245.487.290.473.2110121.486131.2140.64965.8

0050456400 g/Sch20.065.2510.2814.21227.5838.1638.2735.0629.8941.440.643.27397.868.828.64

0050506400 g/Sch20.050.927.213.7953.821.1687.4

0050526400 g/Sch20.150.531.123.884.0411.5116.616.82227.3536.7438.9627.6640.436.6523.5912.74

0050576400 g/Sch20.054.0114.3487.463.888.686.453.8

0060576400 g/Sch20.050.4013.2647.469.0925.5223.7818.1314.9510.9517.23

0070096400 g/Sch20.117.9841.447.4934.3552.4345.6531.3128.1933.4113.9430.113.627.4

0070106400 g/Sch20.120.411.724.853.024.3514.0416.213.9114.5441.6

0070186400 g/Sch20.12110.6615.69

0070216400 g/Sch20.140.731.783.933.5419.7530.7924.9915.5613.2439.436.2313.8640.1928.3210.185.27

0070276400 g/Sch20.070.792.8314.3410.8632.0456.885.434.870.45355.638.1918.87

0070336400 g/Sch20.111.397.276.6610.8313.8811.459.028.9512.5631.4819.088.87

0070346400 g/Sch20.050.871.063.282.35

0070366400 g/Sch20.151.4512.1716.1618.1136.583937.431.9425.7154.442.9225.860.647.421.7510.81

0070396400 g/Sch20.130.881.675.9815.130.61

0080246400 g/Sch20.080.361.8925.426.3230.3649.6345.243.1833.6139.7224.819.728.6831.3114.176.29

0080266400 g/Sch20.131.913.696.6112.594057.250.63778.489.6103.4134.8162.887.882.2

0080296400 g/Sch20.050.080.160.61.092.824.123.643.483.357.454.632.833.894.572.370.89

0080346400 g/Sch20.081.213.718.8511.0540.1375.4146.858.5845.545946.0425.6245.6848.1419.589.45

0090246400 g/Sch20.080.481.121.924.7413.3327.51

0090316400 g/Sch20.183.6955.2

0090366400 g/Sch20.0530.9436.8133.436.860.645.451.647.244.243.452.243.2765.273

0090386400 g/Sch20.140.876.074.564.015.916.826.814.895.290.2814.298.8113.7813.258.924.56

0090446400 g/Sch20.050.210.461.132.734.693.895.254.0617.1311.096.1510.9610.265.183.81

0090486400 g/Sch20.070.685.489.41

0090516400 g/Sch20.052.4823.2227.5823.439.846.250.21394343.4446.9721.4931.8642.3620.278.66

0090526400 g/Sch20.112.934.7911.7812.0632.635.1432.329.1823.3953.394926.58754.831.8518.08

0090546400 g/Sch20.150.584.495.125.9427.4436.9638.4624.1119.2444.0436.5322.1545.0350.8230.912.4

0090556400 g/Sch20.051.498.513.611.531.846.735.7633.7629.847.649.0220.7341.0731.5212.137.03

0010120Placebo/Sch10.080.110.120.150.110.120.170.140.20.170.130.070.10.340.310.12

0010130Placebo/Sch10.080.060.070.090.050.050.080.090.10.060.080.050.050.050.07

0010180Placebo/Sch10.180.10.110.050.170.10.090.180.160.140.10.370.10.850.080.1

0020010Placebo/Sch10.150.10.060.120.070.090.150.120.120.130.170.060.050.090.170.15

0020070Placebo/Sch10.110.110.060.050.080.080.120.10.140.090.050.060.090.130.180.11

0020090Placebo/Sch10.160.20.120.140.110.170.110.170.250.090.120.10.050.240.27

0020120Placebo/Sch10.050.050.050.05

0020140Placebo/Sch10.160.080.090.160.080.160.120.170.170.160.110.130.190.140.19

0020160Placebo/Sch10.070.050.070.080.090.110.110.120.050.120.110.050.050.050.210.06

0020190Placebo/Sch10.090.070.080.160.160.160.120.120.16

0020240Placebo/Sch10.070.050.050.080.070.080.090.060.090.160.090.050.120.050.140.06

0020290Placebo/Sch10.080.080.080.140.150.160.060.10.110.160.130.120.190.130.170.19

0020300Placebo/Sch10.050.060.110.130.160.120.170.070.130.120.10.140.510.520.470.31

0020330Placebo/Sch10.140.160.090.340.170.180.140.10.120.16

0020380Placebo/Sch10.060.050.050.130.10.050.110.120.120.170.060.050.050.110.1

0030020Placebo/Sch10.050.050.050.050.070.060.060.070.130.050.050.150.09

0030030Placebo/Sch10.170.130.2

0040010Placebo/Sch10.070.110.070.28

0040050Placebo/Sch10.050.050.090.180.050.080.320.060.060.060.070.140.050.160.090.05

0050010Placebo/Sch10.060.050.050.050.050.050.050.050.050.05

0050020Placebo/Sch10.120.110.060.050.060.050.050.070.050.10.060.30.090.110.090.1

0050080Placebo/Sch10.190.050.10.130.060.050.120.05

0050100Placebo/Sch10.050.050.090.080.050.050.10.050.050.050.070.20.210.050.080.21

0050140Placebo/Sch10.050.050.050.050.050.050.050.050.080.050.050.050.050.050.050.05

0050210Placebo/Sch10.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05

0050250Placebo/Sch10.050.090.070.050.110.050.080.070.150.140.160.150.090.43

0050280Placebo/Sch10.050.050.050.050.050.050.050.050.050.050.050.050.050.1

0050320Placebo/Sch10.090.050.080.050.110.1

0050330Placebo/Sch10.050.050.050.050.050.050.050.050.050.130.120.050.050.050.050.05

0050380Placebo/Sch10.230.070.20.180.210.050.40.090.080.110.180.190.11

0050390Placebo/Sch10.070.120.130.130.110.140.180.10.10.40.220.130.10.160.220.12

0050400Placebo/Sch10.050.140.050.060.080.110.080.090.120.120.140.120.090.190.130.13

0060100Placebo/Sch10.050.050.050.0590.050.050.050.050.050.050.190.120.080.090.380.17

0060110Placebo/Sch10.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05

0060120Placebo/Sch10.0510.0510.0480.1060.0680.0650.0470.0630.0520.0730.220.160.230.30.360.38

0060230Placebo/Sch10.050.050.050.050.050.050.050.050.050.090.070.050.120.360.10.06

0060410Placebo/Sch10.050.050.050.050.050.0538.770.050.090.090.070.05

0060440Placebo/Sch10.0530.0480.0550.0530.0670.0530.0560.0470.0530.10.060.060.050.280.110.11

0070010Placebo/Sch10.120.140.140.160.120.170.170.170.130.180.190.130.160.140.20.31

0080020Placebo/Sch10.070.110.080.220.210.560.160.120.130.140.320.360.380.20.170.39

0080060Placebo/Sch10.050.050.05

0080070Placebo/Sch10.050.050.080.050.050.050.050.080.060.050.050.060.050.090.120.14

0080090Placebo/Sch10.120.170.130.140.170.170.180.10.10.30.110.190.130.130.150.2

0080110Placebo/Sch10.060.050.420.050.050.060.150.050.050.050.05

0080130Placebo/Sch10.120.120.250.220.170.160.210.250.280.150.170.130.160.150.190.11

0090030Placebo/Sch10.110.090.050.050.09

0090040Placebo/Sch10.180.180.170.180.150.150.270.170.180.220.310.370.260.260.310.25

0090060Placebo/Sch10.050.050.050.050.050.050.050.050.070.060.050.050.050.050.060.05

0090140Placebo/Sch10.050.050.050.050.06

0090190Placebo/Sch10.050.050.050.060.05

0010411Placebo/Sch20.240.270.240.220.160.240.240.210.160.2536.870.210.210.270.30.180.15

0010421Placebo/Sch20.050.080.090.070.090.090.070.080.070.070.070.080.170.440.050.05

0010451Placebo/Sch20.130.050.050.050.050.170.050.050.050.050.050.050.050.260.090.05

0010461Placebo/Sch20.050.060.050.070.080.050.050.070.050.060.050.070.060.230.050.110.05

0010481Placebo/Sch20.120.050.060.060.060.090.140.050.080.060.050.060.050.260.050.069.64

0010561Placebo/Sch20.050.150.170.130.150.150.160.090.260.250.190.110.350.190.110.14

0010611Placebo/Sch20.10.110.10.080.090.080.080.090.090.080.070.070.060.110.050.06

0020411Placebo/Sch20.120.140.050.090.070.130.050.060.050.050.050.130.10.180.230.120.1

0020441Placebo/Sch20.140.260.260.280.250.340.210.250.260.160.210.220.190.250.230.270.15

0020501Placebo/Sch20.060.050.050.080.050.050.050.160.090.050.05

0030051Placebo/Sch20.050.050.050.050.060.050.070.070.070.070.050.050.050.050.050.05

0030181Placebo/Sch20.050.050.050.140.080.180.19

0030191Placebo/Sch20.090.050.050.070.050.150.050.120.1

0030241Placebo/Sch20.150.140.260.190.240.170.190.190.260.260.250.230.290.380.29

0030281Placebo/Sch20.060.13

0030311Placebo/Sch20.180.240.140.140.160.190.150.240.160.110.120.140.310.320.110.34

0030341Placebo/Sch20.110.140.090.050.120.110.10.10.10.130.150.130.110.120.10.53

0030351Placebo/Sch20.050.050.070.110.070.090.110.080.060.060.070.080.150.050.110.11

0030421Placebo/Sch20.050.050.050.060.050.050.110.050.3

0030431Placebo/Sch20.20.10.270.080.43

0030461Placebo/Sch20.10.160.110.180.190.160.120.130.13

0030521Placebo/Sch20.240.130.380.230.30.20.130.090.140.10.090.13

0030541Placebo/Sch20.190.150.090.120.180.110.260.140.110.10.240.170.080.130.190.20.12

0040071Placebo/Sch20.050.070.050.05

0040081Placebo/Sch20.280.30.280.30.340.450.281.480.250.270.340.390.410.350.35

0040121Placebo/Sch20.050.10.10.050.050.06

0040171Placebo/Sch20.050.050.050.050.050.050.050.050.050.050.050.050.060.050.130.050.05

0040241Placebo/Sch20.170.20.140.250.090.270.130.10.190.240.370.150.40.260.280.2

0040271Placebo/Sch20.110.120.270.130.140.180.120.110.160.110.220.110.120.340.290.30.18

0050411Placebo/Sch20.080.240.130.140.170.160.150.130.120.320.260.350.180.450.310.220.21

0070131Placebo/Sch20.050.050.050.050.050.050.050.050.050.090.170.050.05

0070161Placebo/Sch20.050.050.050.050.05

0070171Placebo/Sch20.140.210.310.320.190.240.170.17

0070191Placebo/Sch20.060.050.050.050.050.050.050.050.050.050.070.050.050.05

0070251Placebo/Sch20.120.130.090.150.10.120.110.140.120.060.070.060.080.150.140.11

0070291Placebo/Sch20.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05

0070301Placebo/Sch20.160.110.13

0070311Placebo/Sch20.20.140.20.130.110.140.19

0070321Placebo/Sch20.130.10.120.10.110.160.080.10.10.090.110.190.20.160.120.170.06

0070371Placebo/Sch20.170.330.290.150.20.160.270.230.24

0080191Placebo/Sch20.230.370.270.230.140.210.230.170.240.250.130.270.150.160.210.220.15

0080221Placebo/Sch20.190.30.180.20.20.220.290.130.190.110.150.160.230.290.330.350.2

0080251Placebo/Sch20.080.180.090.090.220.16

0080271Placebo/Sch20.060.070.220.120.230.230.180.060.10.140.070.270.10.130.15

0080311Placebo/Sch20.130.210.170.130.130.120.190.120.110.160.140.120.20.110.10.09

0090231Placebo/Sch20.110.090.120.130.10.080.110.20.180.350.314.680.20.070.260.260.17

0090261Placebo/Sch20.060.060.10.080.070.140.260.110.110.190.160.080.140.080.150.150.13

0090281Placebo/Sch20.160.10.130.140.160.140.250.150.190.30.310.210.150.210.240.260.13

0090421Placebo/Sch20.120.20.180.180.260.160.150.160.330.190.190.170.280.120.150.190.1

0090461Placebo/Sch20.060.110.120.110.170.050.090.120.190.120.060.060.120.110.120.110.08


045678910121314161720222326273036404852

200 g/Schedule 10.09483597560.66795890810.77350342121.7709381794.50471063854.96216546824.32102556537.340143157912.324534427318.053931982213.475375668.78012911818.552334095227.527913161414.2441565067.1256674902

400 g/Schedule 10.08867859291.03636037471.25720722983.79809748627.75681841847.02724284465.752595064915.831948778924.490154644320.647275303717.556768619712.41455344829.61403354134.885670471519.540453356911.1913651892

200 g/Schedule 20.10196497480.90350480683.97681135687.33796758737.981926135114.92823233519.1907395618.788545830118.840338454315.558696697123.128860829725.614652564618.14956192731.498606247432.536040115118.40647120088.4258287124

5 Injections 400 g0.08627781211.17281749963.8936221018.2930724568.555757091319.58005720624.197356208924.597359355820.941241757218.83226130432.708986806936.003218939922.617873966944.403241952543.677727648521.550236473912.2981834995

6 Injections 400 g (est.)0.08627781211.17281749963.8936221018.2930724568.555757091319.58005720624.197356208924.597359355838.541.863.66546.768.567.845.636.4

NicVAX Clinical Development

S h a p i n gt h e F u t u r e o fH E A L T H C A R E


*Objectives of the Phase I/II programEvaluate tolerability and safety of NicVAX in non-smokers and smokersUnderstand the immune response to NicVAXDetermineDose level and number of dosesAdministration scheduleDemonstrate proof of concept that antibodies to nicotine are useful in treating nicotine dependence


*NicVAX Phase 2b Trial DesignMulti-center, randomized, double-blind, placebo controlled study in smokers who want to quit smoking301 heavy smokersAverage of 24 cigarettes per day; no smoker less than 15/day2 dose levels (400 g and 200 g) vs. placebo4 and 5 injection schedules tested and pooled for POC


*Safety & Tolerability SummaryNicVAX was safe with no significant SAEs. No difference between placebo and NicVAXSimilar observations for all other studies to dateMost common local reactogenicity events AcheTendernessMost common systemic reactogenicity eventsGeneral discomfort/malaiseHeadacheMuscle achesEvents were generally mild to moderate in severity and resolved quicklyIncidence of events did not increase after subsequent vaccinations


*Adverse EventsAll events 10% of either NicVAX or Placebo

NicVAX n=201Placebo n=100Upper Respiratory Infection29%30%Headache12%12%Insomnia10%9%Nasopharyngitis9%14%Nausea7%10%Dizziness6%11%


*Antibody Response by Treatment Arm Intent to Treat PopulationTQDTQD4 Injections5 InjectionsSchedule 1 Schedule 2TQD is fixed at 1 week post 2nd injection

gmc ab plot

0.09483597560.08867859290.10196497480.0862778121

0.66795890811.03636037470.90350480681.1728174996

553.97681135683.893622101

0.77350342121.25720722987.33796758738.293072456

1.7709381793.798097486277

887.98192613518.5557570913

4.50471063857.756818418414.92823233519.580057206

4.96216546827.027242844619.1907395624.1973562089

4.32102556535.752595064918.788545830124.5973593558

7.340143157915.83194877891313

12.324534427324.490154644318.840338454320.9412417572

18.053931982220.647275303715.558696697118.832261304

171723.128860829732.7089868069

13.4753756617.556768619725.614652564636.0032189399

8.78012911812.41455344818.14956192722.6178739669

18.552334095229.61403354131.498606247444.4032419525

27.527913161434.885670471532.536040115143.6777276485

14.24415650619.540453356918.406471200821.5502364739

7.125667490211.19136518928.425828712412.2981834995

4 x 200 g

4 x 400 g

5 x 200 g

5 x 400 g

Study Week

GMC Ab (g/ml)

Serology


0010032200 g/Sch10.070.180.170.31.822.111.7411.6612.179.77.824.9821.5619.6694.94

0010042200 g/Sch10.263.13.345.3513.0211.549.3625.9733.333422.5918.110.1532.3321.198.98

0010112200 g/Sch10.2611.5910.2528.6933.2128.2316.6541.258.849.435.634.96140.6183.898.284.8

0010212200 g/Sch10.230.350.370.82

0010232200 g/Sch10.240.340.641.722.795.052.65

0010242200 g/Sch10.170.350.340.993.142.6515.6723.8121.168.6610.2725.9433.7614.629.76

0010252200 g/Sch10.270.430.180.680.620.630.81.11.051.290.670.614.383.420.860.44

0020022200 g/Sch10.1117.712.7411.238.49

0020042200 g/Sch10.230.420.70.631.591.711.85.056.436.044.122.546.567.223.571.92

0020052200 g/Sch10.080.952.2110.5415.2414.4210.3236.1527.633.2717.4213.2333.4543.3717.6111.05

0020132200 g/Sch10.180.140.20.451.241.751.6412.112.98.245.412.115.367.934.783.55

0020152200 g/Sch10.060.420.893.14

0020202200 g/Sch10.135.4222.4148.9649.2147.7225.464.6

0020212200 g/Sch10.130.320.541.239.6712.2912.8236.6646.8742.436.3723.8256.242.631.8914.73

0020222200 g/Sch10.130.550.562.065.424.735.3716.0516.42138.825.1818.0815.546.442.93

0020252200 g/Sch10.081.181.342.597.48.098.1428.3149.639.8229.2620.0259.25020.8815.04

0020262200 g/Sch10.050.210.270.30.690.680.651.388.2718.967.064.1720.4241.7913.424.6

0020312200 g/Sch10.190.782.21

0020352200 g/Sch10.113.462.575.519.8616.3214.6128.6360.258.641.231.4377.25433.423.2

0040042200 g/Sch10.070.220.2732.361.96.246.526.042.882.2618.078.993.522.16

0050062200 g/Sch10.151.131.162.273.2533.296.399.7420.55178.631.854.7525.1112.62

0050092200 g/Sch10.080.210.240.580.761.31

0050132200 g/Sch10.052.432.813.158.216.448.1331.438.9128.9417.8222.8318.5914.917.65

0050172200 g/Sch10.050.380.553.998.6622.427.5353.31106.6185154.873.4123.4225.2196.4

0050182200 g/Sch10.050.340.533.6516.651126.863.0651.435.4581.642.9823.57

0050202200 g/Sch10.220.40.621.783.12

0050242200 g/Sch10.090.460.511.113.793.783.186.516.3912.048.573.376.828.523.761.67

0060032200 g/Sch10.0540.2240.2220.651.7961.8181.4567.5066.37610.727.425.2122.5619.369.716.22

0060072200 g/Sch10.050.1460.1740.2187.56811.5212.8414.0414.09815.42211.177.199.828.655.833.67

0060092200 g/Sch10.050.0640.060.0570.3420.3180.3162.4720.2084.9742.961.79.6510.263.851.84

0060162200 g/Sch10.050.2640.2720.3581.1180.790.7161.2517.21.411.681.224.476.83.842.11

0060252200 g/Sch10.1220.981.511.32613.614.850.0450.050.0539.463322.193339.9319.259.41

0060332200 g/Sch10.050.5340.5860.053.3825.0654.8010.08619.34625.3323.5312.9916.5528.2617.7310.09

0060352200 g/Sch10.0512.3861.9466.2913.0289.768.01817.0260.4325.2818.38

0060392200 g/Sch10.050.1680.1380.1740.2040.04519.8580.31712.2520.460.48

0060482200 g/Sch10.050.0860.0970.1121.2981.298

0060522200 g/Sch10.0480.8581.1824.6385.2264.4785.22418.8731.5132.9218.2419.7526.5535.1220.829.75

0070042200 g/Sch10.110.490.482.314.033.021.468.8521.1621.5411.533.0916.740.718.878.47

0080012200 g/Sch10.055.886.2919.41256284.6185.4205.4490357.8286.2112.4243.4360.4129.275.4

0080052200 g/Sch10.051.161.461.613.524.796.389.7410.589.055.068.922.8913.218.13

0080102200 g/Sch10.050.771.783.412.6710.423.8632.9714.644.8849.425.418.83

0080122200 g/Sch10.10.460.692.175.474.820.2221.3519.1417.312.1435.326.422.1510.41

0080142200 g/Sch10.210.540.951.635.715.718.997.7239.251.234.424.2731.146.23215.52

0080172200 g/Sch10.050.10.180.270.970.781.271.446.163.991.842.2824.448.612.31

0080202200 g/Sch10.11.540.9211.615.7313.769.5429.2930.2122.6213.278.1416.5718.428.454.49

0090052200 g/Sch10.122.072.154.7213.22

0090112200 g/Sch10.350.730.752.7413.9116.3323.0622.847.653.4565373.6106.27745.2

0090122200 g/Sch10.054.943.3610.4310.28

0090152200 g/Sch10.151.312.027.553.777.429.887.335.322.535.674.233.091.68

0090212200 g/Sch10.080.40.485.263.232.231.43

0010363200 g/Sch20.381.6713.8215.0510.189.119.389.418.116.9912.0324.3320.4123.8836.8316.520.06

0010403200 g/Sch20.050.230.691.181.382.212.342.151.941.712.062.291.781.741.460.970.55

0010533200 g/Sch20.392.594.7815.9926.2621.8120.7113.27

0010573200 g/Sch20.050.553.624.895.215.4412.4517.211.97.7621.0415.8721.0524.711.048.51

0020423200 g/Sch20.140.7111.5424.624.8442.842.644.0136.946.94

0030063200 g/Sch20.050.050.130.9910.784.72

0030203200 g/Sch20.080.8914.1586.649.68794.877.251.240.4936.843.9317.1841.7140.9111.977.73

0030393200 g/Sch20.1710.945.388.6215.3535.5424.367.32

0030413200 g/Sch20.252.445.158.9811.629.435.2327.245.9850.842.0947.297.436.521.91

0030443200 g/Sch20.050.7341.1516.624.329938.3133.4733.1552.64227.5839.9440.619.056.53

0030473200 g/Sch20.050.05

0030503200 g/Sch20.133.5992.687.849.847.7159.843.4122.2108.869188.8175.468.234.25

0030533200 g/Sch20.12.1511.8321.7716.1230.0733.1933.1529.3222.8247.2

0030573200 g/Sch23.8523.2517.232.4340.7243.4239.937.544440.438.615971.842.424.07

0040093200 g/Sch20.050.7612.911.8

0040113200 g/Sch20.090.714.759.525.9248.748.5628.8422.5410.3623.9423.5320.62

0040153200 g/Sch20.142.328.6116.0824.75

0040183200 g/Sch20.0818.0826.3946

0040213200 g/Sch20.21.32.7721.1624.6137.5748.6930.3430.2121.2665.860.645.82124.896.6118.631.13

0040263200 g/Sch20.162.333.473.155.176.1110.798.046.995.1410.3611.526.814.9813.836.94.35

0040283200 g/Sch20.10.941.562.064.574.518.9915.5915.3512.0624.3731.1821.450.44939.4525.03

0050433200 g/Sch20.292.8212.4920.5115.8

0050463200 g/Sch20.050.060.140.711.614.1616.3319.8614.77.9417.841.633.0481.494.639.821.71

0050473200 g/Sch20.082.177.434.4733.6240.8446.7546.8437.1935.013550.436.9571.26644.8526.22

0050483200 g/Sch20.130.651.191.861.73.938.368.937.255.629.214.639.51104.263.65

0050513200 g/Sch20.150.211.841.2410.17.787.99

0050543200 g/Sch20.081.481.6321.421.7341.446.253.246.3852.7645.656.444.234565.4930.6319.98

0060563200 g/Sch20.050.1460.694.625.619.9611.3315.910.59.39

0060603200 g/Sch20.05

0070083200 g/Sch20.110.290.650.710.821.321.521.16

0070143200 g/Sch20.132.2825.6124.424.6738.9431.9834.3627.5519.8817.6435.68

0070153200 g/Sch20.112.199.1115.4116.56

0070353200 g/Sch20.051.211.975.487.029.6216.2512.1710.389.13

0080183200 g/Sch20.110.731.170.880.691.251.371.241.180.941.171.180.641.261.170.750.39

0080233200 g/Sch20.274.7830.236.0129.1643.5159.693.883.678.1861.465.257.882.280.444.7719.02

0080283200 g/Sch20.080.692.227.6712.1938.2838.3836.6135.1234.1943.6224.636.9435.7924.8918.987.34

0080323200 g/Sch20.050.331.262.674.3911.3612.999.186.7243.5420.8614.8241.262511.924.79

0080333200 g/Sch20.051.416.1213.416.0131.0232.4628.9329.9537.9648.7932.6633.2350.427.7613.33

0090223200 g/Sch20.241.162.296.1417.5935.6921.422.629.9420.8929.1533.422.7413.39

0090303200 g/Sch20.060.967.879.1521.0431.5251.676.47370.283.8118.484.6128.4125.664.246.21

0090323200 g/Sch20.110.277.535.473.334.997.353.27

0090333200 g/Sch20.181.272.516.97.8422.2425.6922.3817.7818.0327.9641.3332.3782.876.644.3927.38

0090393200 g/Sch20.151.776.168.313.0420.783035.6828.3332.1448.2953.4350.2

0090403200 g/Sch20.050.393.76.755.737.5510.257.928.478.2914.8217.4613.3315.6923.9420.8312.39

0090413200 g/Sch20.051.9210.5510.6413.518.733.7631.232.131.829.843.535.5742.664.438.1918.76

0090433200 g/Sch20.350.380.560.751.274.185.258.215.322.648.1210.956.19

0090473200 g/Sch20.130.252.142.862.3916.081510.289.418.1713.4115.155.0818.5823.856.622.36

0090493200 g/Sch20.072.179.01

0090533200 g/Sch20.060.461.51

0090563200 g/Sch20.13

0010025400 g/Sch10.130.380.742.573.374.443.827.749.56.686.043.58.1511.467.526.04

0010075400 g/Sch10.116.15512281.871.254.49898.268.65038.0764.851.626.6414.78

0010095400 g/Sch10.163.814.626.1434.6527.436.4147.66057.644.239.8967.684.252.3821.44

0010155400 g/Sch10.20.610.974.177.977.424.2816.681624.0114.469.5241.8735.0616.657.73

0010265400 g/Sch10.11.491.354.24

0010275400 g/Sch10.051.282.645.2612.817.6311.329.633.1427.6214.0412.0145.3733.0613.126.25

0010335400 g/Sch10.111.218.7515.0115.244248.5330.1213.0941.1313.4110.32

0020035400 g/Sch10.10.380.8111.0936.5538.1432.3145.5844.2537.8331.9519.641.9940.6536.5925.77

0020105400 g/Sch10.212.553.667.8723.8621.823.8729.0442.475.648.439.6846.63151.811756

0020115400 g/Sch10.112.532.224.884.864.123.539.7212.3615.7213.715.5534.5640.8227.7922.76

0020235400 g/Sch10.161.181.522.062.372.832.4212.8410.6314.439.189.9557.441.1727.6114.6

0020275400 g/Sch10.220.871.18.8715.4514.4315.6342.9442.859.337.0430.5842.442.4432.66

0020345400 g/Sch10.070.740.784.687.026.294.9718.2431.6618.3613.797.3934.922.527.663.41

0020365400 g/Sch10.061.471.961.835.076.4710.7325.846.647.1630.4868.657.4

0020375400 g/Sch10.150.140.352.364.015.1223.168.5753.869.629.0917.11

0040035400 g/Sch10.1344.3315.1338.235.436.2111212203.4156.8139.4225.4243.4122.4132.6

0050055400 g/Sch10.180.330.454.15.134.433.4324.3327.722.515.959.7715.638.8518.110.16

0050075400 g/Sch10.20.470.666.114.483.642.889.7426.2621.638.165.7222.7924.36

0050155400 g/Sch10.073.663.394.879.4611.449.1518.1353.1643.62619.634.274.817.45

0050165400 g/Sch10.160.270.240.260.820.991.53.887.025.886.67.3427.4921.2110.554.13

0050225400 g/Sch10.050.120.130.1811.010.871.652.242.021.090.673.012.991.320.79

0050265400 g/Sch10.051.511.5417.7714.9913.779.422.3132.9925.0614.3327.31

0050275400 g/Sch10.072.762.345.468.077.187.1613.1519.6815.813.148.1515.0410.65.52

0050295400 g/Sch10.050.260.350.641.481.462.8820.9342.2133.0717.7347.7133.3818.498.92

0050305400 g/Sch10.050.10.270.320.881.271.512.233.533.92.92.272.681.670.99

0050315400 g/Sch10.050.370.6711.351.41.613.111.9822.3312.27.114.2412.874.56

0060015400 g/Sch10.050.8541.13.8085.4423.54810.9560.24610.8967.693.6611.9313.484.141.94

0060055400 g/Sch10.22619.34815.25616.57421.01824.89219.47615.846.210.0525.4416.6433.4764.631.5416.42

0060085400 g/Sch10.051.131.3581.5220.5815.12214.2821.08818.7521.78813.29.6328.3125.39.48.95

0060185400 g/Sch10.050.4840.61.9962.2142.172.043

0060295400 g/Sch10.056.82218.354206.8156.2121.481.6173.4139.6103.673.657.6148.4173.264.250.49

0060315400 g/Sch10.050.350.4060.6623.3624.6343.4760.1927.51618.3114.3224.2337.4422.8611.6

0060365400 g/Sch10.050.2560.239

0060385400 g/Sch10.050.2820.3120.3640.5570.730.0564.256

0060475400 g/Sch10.0651.4540.9866.14212.2411.3438.1618.80639.20630.9321.6113.8436.1446.9829.8917.37

0060515400 g/Sch12.8882.9588.87415.5180.1020.0515.99642.4338.1337.6314.863.2107.445.6431.62

0070025400 g/Sch10.110.380.381.282.434.073.297.0114.4411.229.0440.5

0070035400 g/Sch10.13.142.842.6511.3811.177.7436.152.8244.7326.7915.8696943.7626.58

0080035400 g/Sch10.051.822.853.956.887.347.8510.1413.8715.2314.416.3214.6629.0318.9714.75

0080045400 g/Sch10.180.240.370.491.711.762.143.194.253.632.714.3617.869.525.89

0080085400 g/Sch10.0528.5418.2921.2618.39.816.1721.5430.8823.615.2923.1137.22215.39

0080155400 g/Sch10.248.685.8340.834.443.3330.8873.284.86443.647.47104.486.248.848.5

0080165400 g/Sch10.110.580.641.362.192.512.2913.8113.5613.537.34.612.339.264.481.69

0080215400 g/Sch10.070.840.80.9812.8311.5610.552343.0435.8524.7415.7225.832.5923.6915.45

0090025400 g/Sch10.05

0090085400 g/Sch10.050.460.4910.4353.543016.54

0090095400 g/Sch10.056.839.9444.746466.652.28898.854

0090135400 g/Sch10.110.390.720.855.625.45.0722.7729.2621.4224.3819.090.7844.1137.4917.6

0090205400 g/Sch10.130.570.921.243.524.474.588.4513.8715.9813.929.9617.3626.2719.236.67

0090255400 g/Sch10.11.651.288.0320.41

0010316400 g/Sch20.312.874.2122.1916.841.1938.637.633.640.754.4403162.7858.7744.428.23

0010356400 g/Sch20.050.420.872.442.254.299.8914.6114.449.827.1624.4219.96

0010386400 g/Sch20.110.4214.8414.379.611.2225.3325.1125.3222.0625.625.5828.249.0352.3225.0714.95

0010396400 g/Sch20.051.392.87.397.4916.7214.4714.2212.61

0010496400 g/Sch20.11.889.5423.62

0020406400 g/Sch20.150.951.874.44

0020436400 g/Sch20.11

0030076400 g/Sch20.050.150.330.654.5110.28.6310.386.6413.6717.578.0424.7718.2611.385.83

0030116400 g/Sch20.050.714.076.34

0030136400 g/Sch20.173.7216.8659.6962.47871.445.450.3

0030176400 g/Sch20.057.3960.294.645131151175.4219163.6357.6395.8245.2539666.4224.676

0030226400 g/Sch20.074.87

0030236400 g/Sch20.161.161.935.535.1224.0421.524.1920.7417.1944.3828.2119.664239.5218.0416.75

0030296400 g/Sch20.051.783.422.237.098.525.193.852.5619.114.664.7610.0310.894.032.4

0030306400 g/Sch20.05

0030326400 g/Sch20.153.15.066.5420.9132.446.4537.1231.561.84635.685.4100.635.9334.35

0030386400 g/Sch20.361.322.2512.5936.5137.6136.9938.3634.9158.6144.6106172.6222137.498.6

0030496400 g/Sch20.050.613.163.314.5914.0113.319.0133.6119.111.9624.8721.469.036.85

0030586400 g/Sch20.051.342.161.851.434.384.243.172.72.039.376.473.712.4614.628.653.53

0040146400 g/Sch20.051.491.823.71418.4226.8928.7517.0114.6926.4441.2929.259.484.25237.48

0040196400 g/Sch20.122.8135.431.242.431.19

0040206400 g/Sch20.140.22

0040236400 g/Sch20.0548.3815.0830.2949.2245.487.290.473.2110121.486131.2140.64965.8

0050456400 g/Sch20.065.2510.2814.21227.5838.1638.2735.0629.8941.440.643.27397.868.828.64

0050506400 g/Sch20.050.927.213.7953.821.1687.4

0050526400 g/Sch20.150.531.123.884.0411.5116.616.82227.3536.7438.9627.6640.436.6523.5912.74

0050576400 g/Sch20.054.0114.3487.463.888.686.453.8

0060576400 g/Sch20.050.4013.2647.469.0925.5223.7818.1314.9510.9517.23

0070096400 g/Sch20.117.9841.447.4934.3552.4345.6531.3128.1933.4113.9430.113.627.4

0070106400 g/Sch20.120.411.724.853.024.3514.0416.213.9114.5441.6

0070186400 g/Sch20.12110.6615.69

0070216400 g/Sch20.140.731.783.933.5419.7530.7924.9915.5613.2439.436.2313.8640.1928.3210.185.27

0070276400 g/Sch20.070.792.8314.3410.8632.0456.885.434.870.45355.638.1918.87

0070336400 g/Sch20.111.397.276.6610.8313.8811.459.028.9512.5631.4819.088.87

0070346400 g/Sch20.050.871.063.282.35

0070366400 g/Sch20.151.4512.1716.1618.1136.583937.431.9425.7154.442.9225.860.647.421.7510.81

0070396400 g/Sch20.130.881.675.9815.130.61

0080246400 g/Sch20.080.361.8925.426.3230.3649.6345.243.1833.6139.7224.819.728.6831.3114.176.29

0080266400 g/Sch20.131.913.696.6112.594057.250.63778.489.6103.4134.8162.887.882.2

0080296400 g/Sch20.050.080.160.61.092.824.123.643.483.357.454.632.833.894.572.370.89

0080346400 g/Sch20.081.213.718.8511.0540.1375.4146.858.5845.545946.0425.6245.6848.1419.589.45

0090246400 g/Sch20.080.481.121.924.7413.3327.51

0090316400 g/Sch20.183.6955.2

0090366400 g/Sch20.0530.9436.8133.436.860.645.451.647.244.243.452.243.2765.273

0090386400 g/Sch20.140.876.074.564.015.916.826.814.895.290.2814.298.8113.7813.258.924.56

0090446400 g/Sch20.050.210.461.132.734.693.895.254.0617.1311.096.1510.9610.265.183.81

0090486400 g/Sch20.070.685.489.41

0090516400 g/Sch20.052.4823.2227.5823.439.846.250.21394343.4446.9721.4931.8642.3620.278.66

0090526400 g/Sch20.112.934.7911.7812.0632.635.1432.329.1823.3953.394926.58754.831.8518.08

0090546400 g/Sch20.150.584.495.125.9427.4436.9638.4624.1119.2444.0436.5322.1545.0350.8230.912.4

0090556400 g/Sch20.051.498.513.611.531.846.735.7633.7629.847.649.0220.7341.0731.5212.137.03

0010120Placebo/Sch10.080.110.120.150.110.120.170.140.20.170.130.070.10.340.310.12

0010130Placebo/Sch10.080.060.070.090.050.050.080.090.10.060.080.050.050.050.07

0010180Placebo/Sch10.180.10.110.050.170.10.090.180.160.140.10.370.10.850.080.1

0020010Placebo/Sch10.150.10.060.120.070.090.150.120.120.130.170.060.050.090.170.15

0020070Placebo/Sch10.110.110.060.050.080.080.120.10.140.090.050.060.090.130.180.11

0020090Placebo/Sch10.160.20.120.140.110.170.110.170.250.090.120.10.050.240.27

0020120Placebo/Sch10.050.050.050.05

0020140Placebo/Sch10.160.080.090.160.080.160.120.170.170.160.110.130.190.140.19

0020160Placebo/Sch10.070.050.070.080.090.110.110.120.050.120.110.050.050.050.210.06

0020190Placebo/Sch10.090.070.080.160.160.160.120.120.16

0020240Placebo/Sch10.070.050.050.080.070.080.090.060.090.160.090.050.120.050.140.06

0020290Placebo/Sch10.080.080.080.140.150.160.060.10.110.160.130.120.190.130.170.19

0020300Placebo/Sch10.050.060.110.130.160.120.170.070.130.120.10.140.510.520.470.31

0020330Placebo/Sch10.140.160.090.340.170.180.140.10.120.16

0020380Placebo/Sch10.060.050.050.130.10.050.110.120.120.170.060.050.050.110.1

0030020Placebo/Sch10.050.050.050.050.070.060.060.070.130.050.050.150.09

0030030Placebo/Sch10.170.130.2

0040010Placebo/Sch10.070.110.070.28

0040050Placebo/Sch10.050.050.090.180.050.080.320.060.060.060.070.140.050.160.090.05

0050010Placebo/Sch10.060.050.050.050.050.050.050.050.050.05

0050020Placebo/Sch10.120.110.060.050.060.050.050.070.050.10.060.30.090.110.090.1

0050080Placebo/Sch10.190.050.10.130.060.050.120.05

0050100Placebo/Sch10.050.050.090.080.050.050.10.050.050.050.070.20.210.050.080.21

0050140Placebo/Sch10.050.050.050.050.050.050.050.050.080.050.050.050.050.050.050.05

0050210Placebo/Sch10.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05

0050250Placebo/Sch10.050.090.070.050.110.050.080.070.150.140.160.150.090.43

0050280Placebo/Sch10.050.050.050.050.050.050.050.050.050.050.050.050.050.1

0050320Placebo/Sch10.090.050.080.050.110.1

0050330Placebo/Sch10.050.050.050.050.050.050.050.050.050.130.120.050.050.050.050.05

0050380Placebo/Sch10.230.070.20.180.210.050.40.090.080.110.180.190.11

0050390Placebo/Sch10.070.120.130.130.110.140.180.10.10.40.220.130.10.160.220.12

0050400Placebo/Sch10.050.140.050.060.080.110.080.090.120.120.140.120.090.190.130.13

0060100Placebo/Sch10.050.050.050.0590.050.050.050.050.050.050.190.120.080.090.380.17

0060110Placebo/Sch10.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05

0060120Placebo/Sch10.0510.0510.0480.1060.0680.0650.0470.0630.0520.0730.220.160.230.30.360.38

0060230Placebo/Sch10.050.050.050.050.050.050.050.050.050.090.070.050.120.360.10.06

0060410Placebo/Sch10.050.050.050.050.050.0538.770.050.090.090.070.05

0060440Placebo/Sch10.0530.0480.0550.0530.0670.0530.0560.0470.0530.10.060.060.050.280.110.11

0070010Placebo/Sch10.120.140.140.160.120.170.170.170.130.180.190.130.160.140.20.31

0080020Placebo/Sch10.070.110.080.220.210.560.160.120.130.140.320.360.380.20.170.39

0080060Placebo/Sch10.050.050.05

0080070Placebo/Sch10.050.050.080.050.050.050.050.080.060.050.050.060.050.090.120.14

0080090Placebo/Sch10.120.170.130.140.170.170.180.10.10.30.110.190.130.130.150.2

0080110Placebo/Sch10.060.050.420.050.050.060.150.050.050.050.05

0080130Placebo/Sch10.120.120.250.220.170.160.210.250.280.150.170.130.160.150.190.11

0090030Placebo/Sch10.110.090.050.050.09

0090040Placebo/Sch10.180.180.170.180.150.150.270.170.180.220.310.370.260.260.310.25

0090060Placebo/Sch10.050.050.050.050.050.050.050.050.070.060.050.050.050.050.060.05

0090140Placebo/Sch10.050.050.050.050.06

0090190Placebo/Sch10.050.050.050.060.05

0010411Placebo/Sch20.240.270.240.220.160.240.240.210.160.2536.870.210.210.270.30.180.15

0010421Placebo/Sch20.050.080.090.070.090.090.070.080.070.070.070.080.170.440.050.05

0010451Placebo/Sch20.130.050.050.050.050.170.050.050.050.050.050.050.050.260.090.05

0010461Placebo/Sch20.050.060.050.070.080.050.050.070.050.060.050.070.060.230.050.110.05

0010481Placebo/Sch20.120.050.060.060.060.090.140.050.080.060.050.060.050.260.050.069.64

0010561Placebo/Sch20.050.150.170.130.150.150.160.090.260.250.190.110.350.190.110.14

0010611Placebo/Sch20.10.110.10.080.090.080.080.090.090.080.070.070.060.110.050.06

0020411Placebo/Sch20.120.140.050.090.070.130.050.060.050.050.050.130.10.180.230.120.1

0020441Placebo/Sch20.140.260.260.280.250.340.210.250.260.160.210.220.190.250.230.270.15

0020501Placebo/Sch20.060.050.050.080.050.050.050.160.090.050.05

0030051Placebo/Sch20.050.050.050.050.060.050.070.070.070.070.050.050.050.050.050.05

0030181Placebo/Sch20.050.050.050.140.080.180.19

0030191Placebo/Sch20.090.050.050.070.050.150.050.120.1

0030241Placebo/Sch20.150.140.260.190.240.170.190.190.260.260.250.230.290.380.29

0030281Placebo/Sch20.060.13

0030311Placebo/Sch20.180.240.140.140.160.190.150.240.160.110.120.140.310.320.110.34

0030341Placebo/Sch20.110.140.090.050.120.110.10.10.10.130.150.130.110.120.10.53

0030351Placebo/Sch20.050.050.070.110.070.090.110.080.060.060.070.080.150.050.110.11

0030421Placebo/Sch20.050.050.050.060.050.050.110.050.3

0030431Placebo/Sch20.20.10.270.080.43

0030461Placebo/Sch20.10.160.110.180.190.160.120.130.13

0030521Placebo/Sch20.240.130.380.230.30.20.130.090.140.10.090.13

0030541Placebo/Sch20.190.150.090.120.180.110.260.140.110.10.240.170.080.130.190.20.12

0040071Placebo/Sch20.050.070.050.05

0040081Placebo/Sch20.280.30.280.30.340.450.281.480.250.270.340.390.410.350.35

0040121Placebo/Sch20.050.10.10.050.050.06

0040171Placebo/Sch20.050.050.050.050.050.050.050.050.050.050.050.050.060.050.130.050.05

0040241Placebo/Sch20.170.20.140.250.090.270.130.10.190.240.370.150.40.260.280.2

0040271Placebo/Sch20.110.120.270.130.140.180.120.110.160.110.220.110.120.340.290.30.18

0050411Placebo/Sch20.080.240.130.140.170.160.150.130.120.320.260.350.180.450.310.220.21

0070131Placebo/Sch20.050.050.050.050.050.050.050.050.050.090.170.050.05

0070161Placebo/Sch20.050.050.050.050.05

0070171Placebo/Sch20.140.210.310.320.190.240.170.17

0070191Placebo/Sch20.060.050.050.050.050.050.050.050.050.050.070.050.050.05

0070251Placebo/Sch20.120.130.090.150.10.120.110.140.120.060.070.060.080.150.140.11

0070291Placebo/Sch20.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.050.05

0070301Placebo/Sch20.160.110.13

0070311Placebo/Sch20.20.140.20.130.110.140.19

0070321Placebo/Sch20.130.10.120.10.110.160.080.10.10.090.110.190.20.160.120.170.06

0070371Placebo/Sch20.170.330.290.150.20.160.270.230.24

0080191Placebo/Sch20.230.370.270.230.140.210.230.170.240.250.130.270.150.160.210.220.15

0080221Placebo/Sch20.190.30.180.20.20.220.290.130.190.110.150.160.230.290.330.350.2

0080251Placebo/Sch20.080.180.090.090.220.16

0080271Placebo/Sch20.060.070.220.120.230.230.180.060.10.140.070.270.10.130.15

0080311Placebo/Sch20.130.210.170.130.130.120.190.120.110.160.140.120.20.110.10.09

0090231Placebo/Sch20.110.090.120.130.10.080.110.20.180.350.314.680.20.070.260.260.17

0090261Placebo/Sch20.060.060.10.080.070.140.260.110.110.190.160.080.140.080.150.150.13

0090281Placebo/Sch20.160.10.130.140.160.140.250.150.190.30.310.210.150.210.240.260.13

0090421Placebo/Sch20.120.20.180.180.260.160.150.160.330.190.190.170.280.120.150.190.1

0090461Placebo/Sch20.060.110.120.110.170.050.090.120.190.120.060.060.120.110.120.110.08


0456789101213141617202627304052

4 x 200 g0.09483597560.66795890810.77350342121.7709381794.50471063854.96216546824.32102556537.340143157912.324534427318.053931982213.475375668.78012911818.552334095227.527913161414.2441565067.1256674902

4 x 400 g0.08867859291.03636037471.25720722983.79809748627.75681841847.02724284465.752595064915.831948778924.490154644320.647275303717.556768619712.41455344829.61403354134.885670471519.540453356911.1913651892

5 x 200 g0.10196497480.90350480683.97681135687.33796758737.981926135114.92823233519.1907395618.788545830118.840338454315.558696697123.128860829725.614652564618.14956192731.498606247432.536040115118.40647120088.4258287124

5 x 400 g0.08627781211.17281749963.8936221018.2930724568.555757091319.58005720624.197356208924.597359355820.941241757218.83226130432.708986806936.003218939922.617873966944.403241952543.677727648521.550236473912.2981834995


*Proportion of Subjects Quit Each Week: Point Prevalence Stratified by Antibody Levels*Top 30% by AUCN=18/61p=0.0055N=17/140N=12/100All NicVAX Subjects: ITTTQDTQD

wk pp 52

00.71.7

00.71.7

00.73.4

01.43.4

610.613.6

810.616.9

1616.233.9

1516.232.2

1314.135.6

1819.739

1515.537.3

1815.533.9

1613.433.9

1915.537.3

1515.533.9

161933.9

1916.935.6

2215.533.9

181232.2

1916.235.6

2115.535.6

1815.535.6

1816.239

1917.635.6

1614.832.2

1415.532.2

171930.5

1918.333.9

1815.535.6

1816.235.6

2016.235.6

2015.535.6

2016.935.6

2016.937.3

1815.537.3

1816.237.3

1616.935.6

1915.539

1412.733.9

1513.437.3

1713.437.3

1613.433.9

1813.433.9

1613.433.9

1713.432.2

1512.732.2

151232.2

1513.432.2

1514.132.2

1612.732.2

121230.54

placebo

low Ab

high Ab*

Study Week

% Quit per Week

Sheet1

200.71.7

300.71.7

400.73.4

501.43.4

6610.613.6

7810.616.9

81616.233.9

91516.232.2

101314.135.6

111819.739

121515.537.3

131815.533.9

141613.433.9

151915.537.3

161515.533.9

17161933.9

181916.935.6

192215.533.9

20181232.2

211916.235.6

222115.535.6

231815.535.6

241816.239

251917.635.6

261614.832.2

271415.532.2

28171930.5

291918.333.9

301815.535.6

311816.235.6

322016.235.6

332015.535.6

342016.935.6

352016.937.3

361815.537.3

371816.237.3

381616.935.6

391915.539

401412.733.9

411513.437.3

421713.437.3

431613.433.9

441813.433.9

451613.433.9

461713.432.2

471512.732.2

48151232.2

491513.432.2

501514.132.2

511612.732.2

52121230.54

Sheet2

Sheet3


*Antibody-dependence of Abstinence : ITTPrimary Endpoint (POC) and Follow up* Top 30% by AUC per protocolSchedule 1 & Schedule 2 pooled

Continuous Abstinence6-Month (8Wk 19-26)12-Month 44-WeekNicVAX High Antibody*25%(n=15/61)p=0.0418%(n=11/61)p=0.01NicVAX Low Antibody10% (n=14/140)p=0.478%(n=11/140)p=0.49Placebo 13% (n=13/100)6% (n=6/100)


***NicVAX Long-term Efficacy before Regimen Optimization Similar to Marketed Rx Therapies Intent to Treat Population in all casesIntended for comparative purposes only & does not reflect head to head study

Treatment44-Week Continuous Abstinence ActivePlaceboTherapeutic Effectvarenicline (Chantix) Pfizer Phase III 21-22%8-10%13%OR=3.13bupropion (Zyban) Pfizer Phase III comparator arm14-16%8-10%6%OR=

NicVAX

Correlation between Antibody Levels and Smoking Cessation

Phase IIbS h a p i n gt h e F u t u r e o fH E A L T H C A R E


*High Antibody Levels Support Sustained Quit in 5 Injection Regimen (Nabi-4512)N=12/30N=8/71N=12/100NicVAX Subjects: 5 Injection RegimenTQDQuit for at least 8 weeks continuously and remaining continuously abstinent to study end

RawAUC Plot

000

000

27.042253521123.3333333333

27.042253521123.3333333333

38.450704225426.6666666667

38.450704225426.6666666667

511.267605633830

511.267605633830

611.267605633833.3333333333

633.3333333333

736.6666666667

736.6666666667

840

840

940

9

10

10

11

11

12

12

12

p=0.0068 comparing top 30% in AUC to placebo in a Cox model adjusted for center

Placebo

Bottom 70% in AUC

Top 30% in AUC

Time to Sustained Abstinence (Weeks)

Sustained Abstinence

ImpuAUC Plot

000

000

28.450704225420

28.450704225420

39.859154929623.3333333333

39.859154929623.3333333333

512.67605633826.6666666667

512.67605633826.6666666667

612.67605633830

630

733.3333333333

733.3333333333

836.6666666667

836.6666666667

936.6666666667

9

10

10

11

11

12

12

12

p=0.0008 comparing top 30% in AUC to placebo in a Cox model adjusted for center

Placebo

Bottom 70% in AUC

Top 30% in AUC

Time to 8-Week Sustained Abstinence (Weeks)

% 8-Week Sustained Abstinence

Kaplan-Meier Estimates of Time to 8-Week Sustained Abstinence Stratified by Imputed AUC(0-26w) (>= 4994.82, < 4994.82, placebo, Log-rank p-value = 0.0024) - NicVAX Schedule 2 and Placebo SubjectsDropouts Censored at Week 52

RawAUC Data

AUCRawGroupFirstQuit8Wksurvivalfailure_CENSOR_

0010000

061000

069820

07982

079730

08973

089550

09955

099460

010946

0109370

011937

0119280

012928

0129190

016919

01690100

0259010

02589110

0298911

02988120

0528812

05288121

1010000

161000

1692.95774647897.04225352110

1792.95774647897.0422535211

1791.54929577468.45070422540

12191.54929577468.4507042254

12188.732394366211.26760563380

15288.732394366211.2676056338

15288.732394366211.26760563381

2010000

261000

2676.666666666723.33333333330

2776.666666666723.3333333333

2773.333333333326.66666666670

22173.333333333326.6666666667

22170300

2297030

22966.666666666733.33333333330

23166.666666666733.3333333333

23163.333333333336.66666666670

23563.333333333336.6666666667

23560400

2526040

25260401

ImpuAUC Data

AUCImpuGroupFirstQuit8Wksurvivalfailure_CENSOR_

0010000

061000

069820

07982

079730

08973

089550

09955

099460

010946

0109370

011937

0119280

012928

0129190

016919

01690100

0259010

02589110

0298911

02988120

0528812

05288121

1010000

161000

1691.54929577468.45070422540

1791.54929577468.4507042254

1790.14084507049.85915492960

12190.14084507049.8591549296

12187.32394366212.6760563380

15287.32394366212.676056338

15287.32394366212.6760563381

2010000

261000

2680200

278020

2776.666666666723.33333333330

22176.666666666723.3333333333

22173.333333333326.66666666670

22973.333333333326.6666666667

22970300

2317030

23166.666666666733.33333333330

23566.666666666733.3333333333

23563.333333333336.66666666670

25263.333333333336.6666666667

25263.333333333336.66666666671


*Antibody Dose-Response (Abstinence at 12-months)Top 30%NicVAX Subjects: 5 Injection Regimen

mean

19.8

21.11

23.75

22.86

23.33

28

30

40

50

70

Mean

Percentile Group ranked by Cmax Ab level

8wk CARweeks 45-52

min value

16.25

15.71

15

18

20

26.67

35

50

Min Value

Log10 Week 16 Ab level

% quit last 8 weeks (45-52)

both

14.8547.06847.068

15.5647.65147.651

16.2548.5148.51

15.7149.73349.733

1551.33151.331

1853.97653.976

2058.46258.462

26.6764.69564.695

3574.15974.159

50

Documents

NicVAX; An Immunotherapy Aid to Smoking Cessation and Long Term Abstinence February 27, 2011 Raafat Fahim, Ph.D. President and CEO, Nabi Biopharmaceuticals