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

S h a p i n g t h e F u t u r e o f H E A L T H C A R E. NicVAX ; An Immunotherapy Aid to Smoking Cessation and Long Term Abstinence February 27, 2011 Raafat Fahim, Ph.D. President and CEO, Nabi Biopharmaceuticals. NicVAX; Significant Unmet Need. Smoking Impact 1.3 billion smokers

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

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  1. Shaping t h e Future o f H E A L T H C A R E NicVAX; An Immunotherapy Aid to Smoking Cessation and Long Term AbstinenceFebruary 27, 2011Raafat Fahim, Ph.D. President and CEO, Nabi Biopharmaceuticals

  2. NicVAX; Significant Unmet Need Smoking Impact 1.3 billion smokers Currently, 44 million adult smokers in the U.S. >75% start smoking cigarettes before the age of 18 5.4 million deaths/year worldwide Smoking 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 costs2 The Consumer Average former smoker makes 8 to 11 attempts to quit Only 3–5% of all smokers who try to quit by themselves are permanently successful on any given attempt 4

  3. Why do people fail to quit long-term? • Addiction • <10% (<1:10) remain abstinent at one-year who quit “cold-turkey” • Cravings • Nicotine is freely available and more socially acceptable than other addictive drugs • Habit/psychological cues • Current therapies in combination with behavioral counseling • One-year continuous abstinence rates: best is ~22% • Short-acting • Compliance • Side-effect concerns

  4. NicVAX: 3’aminomethyl Nicotine – Recombinant P. aeruginosa Exoprotein A (rEPA) Conjugate N H 2 N C H 3 N N C H 3 N Nicotine is not immunogenic O rEPA + + H N O 2 Nicotine O 3’ aminomethyl Nicotine AMNic rEPA O Upon conjugation to rEPA (NicVAX ) nicotine is rendered immunogenic N H rEPA N H O N C H 3 N + alum (Adjuvant)

  5. Breaking the Addiction Cycle

  6. NicVAX Induces Antibodies Specific to Nicotine, Not to Nicotine Metabolites or Related Molecules Specificity, (binding) of antibodies to nicotine induced by vaccination with NicVAX Specificity was determined by inhibition ELISA nd=not determined

  7. Shaping t h e Future o f H E A L T H C A R E NicVAXPreclinical Studies and Theoretical Mechanism of Action (Clinical relevance unknown)

  8. 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

  9. 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 Pentel et al SRNT 2005

  10. In Animal Models, NicVAX Demonstrated Consistent Efficacy Antibodies to NicVAX Neutralized the pharmacological effects of nicotine on blood pressure1 locomotor activity2 nicotine discrimination3 diminishes NSA4 Prevented drug dependence and addiction when administered prophylactically5 Administration during nicotine exposure prevented onset of withdrawal symptoms in animals6 1Pharm Biochem Behav 2000;66:191 2Bioorg Med Chem 2004;12:563 3Life Sci 2002;70:2793 4LeSage et.al Psychopharmacology 2005 5Resp 2002;69(3):247 6Pharm Biochem Behav 2001:68:87

  11. NicVAX Elicited Polyclonal Antibodies Display “Monoclonal-like” Specificity : > 90% Competitive Inhibition with a Single NicVAX mAb Rabbit Rat NicVAX Mc-431 (Competitor) against Polyclonal Antibodies (Primary) on 3’AMNic-Coated Plates

  12. “Monoclonal Nature” also Observed in NicVAX Immunized Subjects

  13. Untreated Smoker Upon smoking; nicotine travels quickly to the brain illustrative illustrative

  14. Path to Continuous Abstinence along with the Potential to Reduce Cravings and Withdrawals Effective number of cigarettes “seen” by the brain decreases with time, making it easier to quit … illustrative Antibodies partially shield the brain from nicotine

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

  16. Shaping t h e Future o f H E A L T H C A R E NicVAXClinical Development

  17. Objectives of the Phase I/II program • Evaluate tolerability and safety of NicVAX in non-smokers and smokers • Understand the immune response to NicVAX • Determine • Dose level and number of doses • Administration schedule • Demonstrate proof of concept that antibodies to nicotine are useful in treating nicotine dependence

  18. NicVAX Phase 2b Trial Design • Multi-center, randomized, double-blind, placebo controlled study in smokers who want to quit smoking • 301 heavy smokers • Average of 24 cigarettes per day; no smoker less than 15/day • 2 dose levels (400 µg and 200 µg) vs. placebo • 4 and 5 injection schedules tested and pooled for POC

  19. Safety & Tolerability Summary • NicVAX was safe with no significant SAEs. No difference between placebo and NicVAX • Similar observations for all other studies to date • Most common local reactogenicity events • Ache • Tenderness • Most common systemic reactogenicity events • General discomfort/malaise • Headache • Muscle aches • Events were generally mild to moderate in severity and resolved quickly • Incidence of events did not increase after subsequent vaccinations

  20. Adverse Events All events ≥ 10% of either NicVAX or Placebo

  21. Antibody Response by Treatment ArmIntent to Treat Population TQD TQD 4 Injections Schedule 1 5 Injections Schedule 2 TQD is fixed at 1 week post 2nd injection

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

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

  24. NicVAX Long-term Efficacy before Regimen Optimization Similar to Marketed Rx Therapies Intent to Treat Population in all cases Intended for comparative purposes only & does not reflect head to head study 25 25

  25. Shaping t h e Future o f H E A L T H C A R E NicVAXCorrelation between Antibody Levels and Smoking CessationPhase IIb

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

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

  28. NicVAX ITT : Ab Levels after Each Injection Correlate with LT Efficacy 3rd Injection 2nd Injection 4th Injection 29

  29. Antibody-Dependent Reduction in Cigarette Consumption in Non-Abstainers All NicVAX Subjects: ITT

  30. Reduced Clinical/Regulatory Pathway Risk • Successful EOP2 meeting with the FDA: • No concerns with pre-clinical safety or CMC to initiate phase III studies • Agreed with phase III design and end points • Encouraged Nabi to submit an SPA • Approved SPA package: • FDA approved design and end points in a letter to Nabi • Received scientific advice from EMA • Supports Phase III trial design • Pivotal Phase 3 studies initiated • First trial November 2, 2009 – Results anticipated 2nd half, 2011 • Second trial March 17, 2010 – Results anticipated 1st half, 2012 31

  31. Responders % Above Target Ab levels by Number of Injections ITT Population Nabi-4513 vs. Nabi-4512 TQD TQD 83% 50% 7%

  32. Key Findings: Implications for NicVAX Phase III Trial Design The 400 µg doses induce high antibody levels Six doses maintain long-term, high antibody levels in circulation => Abstinence is sustained to 12 months Alignment of target quit date with peak antibody levels will enhance effectiveness => move TQD to Week 14 (previously Week 5) Additional dose at week 12 further increase Ab levels earlier; evaluated in a separate study prior to phase III Increasing supportive counseling consistent with other marketed therapies may improve abstinence rates Vaccine education incorporated in the study 33

  33. Principal Design Changes for Phase III Phase IIb Proof-of-Concept • Five injections, 400 µg, at weeks 0,4,8,16 & 26 • Target Quit Date Week 5 • One trial x 301 participants • 8 research sites • Smoke ≥ 15 cigarettes /day • Minimal counseling Phase III Efficacy/Safety • Six injections, 400 µg at weeks 0,4,8, 12, 16 & 26 • Target Quit Date Week 14 • 2 trials x 1000 participants • 22 and 25 research sites • Smoke ≥ 10 cigarettes/day • Standard-of-care counseling • Aligned with Target Quit Date and high antibody level

  34. Phase III Studies • Two multi-center, double-blind, placebo-controlled randomized trials, Nabi-4514 and Nabi-4515 • Nearly identical trials, 1000 patients each • 22 to 25 sites per study • Mix of academic medical center-based and community-based sites

  35. Nabi-4514 & Nabi-4515: DB, Placebo-controlled Phase III Studies to Assess NicVAX as an Aid to Smoking Cessation & Long-term Abstinence TQD NicVAX Injections 12 4 8 16 26 0 52 Four injections supports quitting at TQD Six injections series supports long-term abstinence + placebo injections 4 months of abstinence 1o Endpoint Abstinence at one year

  36. NicVAX Licensed to GlaxoSmithKline • Exclusive worldwide option and licensing agreement to: • Develop, commercialize and manufacture NicVAX & NicVAX Alternatives • Develop, commercialize and manufacture future generation vaccines • More than $500 million upfront and potential consideration • Transaction closed • Approved by Nabi shareholders March 2, 2010 • Agreement closed March 8, 2010

  37. Status of Efficacy Studies • Two 1000 Subject Phase III studies on-going • 1st Study, Completion of enrollment announced: July 2010 • 2nd Study, Completion of enrollment announced: November 2010 • Anticipate final results of 1st Phase III (Nabi-4514) in 2nd half of 2011 • Anticipate final results of 2nd Phase III (Nabi-4515) in 1st half of 2012

  38. Summary • NicVAX holds potential as an additional aid to smoking cessation and relapse prevention • Reduced clinical risk • Dose selected and optimized regimen established • Aligned target quit date with peak antibody levels • Reduced regulatory risk • Both Phase III studies initiated • SPA approved by FDA • Scientific advice from EMEA • Reduced commercial risk • GSK’s worldwide commercialization reach • Well positioned to be first smoking cessation vaccine to market “Shifting the smoking-cessation therapeutic paradigm from quit to continuous abstinence”

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