Post on 03-Jan-2016
transcript
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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*Monoclonal Nature also Observed in NicVAX Immunized Subjects
Nabi Biopharmaceuticals Confidential and Proprietary
*Upon smoking; nicotine travels quickly to the brainUntreated Smokerillustrativeillustrative
Day 01 Month2 Month3 Month4 Month
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Day 01 Month2 Month3 Month4 Month
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
SUBJIDTCDTCDTXTW0W4W5W6W7W8W9W10W12W13W14W16W17W20W26W27W30W40W52
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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Day 01 Month2 Month3 Month4 Month
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
SUBJIDTCDTCDTXTW0W4W5W6W7W8W9W10W12W13W14W16W17W20W26W27W30W40W52
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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*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%
Nabi Biopharmaceuticals Confidential and Proprietary
*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
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
SUBJIDTCDTCDTXTW0W4W5W6W7W8W9W10W12W13W14W16W17W20W26W27W30W40W52
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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*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)
Nabi Biopharmaceuticals Confidential and Proprietary
***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
Nabi Biopharmaceuticals Confidential and Proprietary
*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
Nabi Biopharmaceuticals Confidential and Proprietary
*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