 Sunday, September 18, 2011 ICAAC Chicago, IL An Observer-Blinded, Randomized, Parallel-Group, Multi- Center Study Comparing the Safety and Immunogenicity of HEPLISAV to Licensed Vaccine (Engerix-B®) among Healthy Subjects 40 to 70 Years of Age Exhibit 99.2 |
 Background: HBV in older adults HBV Vaccination for adults is recommended for persons at increased risk of infection Current HBV vaccines are less immunogenic in healthy adults age 40+ (Averhoff, AJPrevMed, 1998) There has been no decrease in the rate of HBV infection in adults age 40-59 in the US from 1988-2008 (McQuillan, NCHS Data Brief, 2010) >40% of reported acute HBV infections in the US occur in adults age 40+ (MMWR, 2009) >50% of reported acute HBV infections in Germany occur in adults age 40+ (RKI, 2011) |
 Introduction: HBV Vaccine Current licensed Hepatitis B virus (HBV) vaccine Contains 20 µg HBsAg adjuvanted with aluminum hydroxide Administered in 3 doses on a 0,1, 6 month schedule HBsAg+ISS (HEPLISAV) Contains a new class of adjuvant (1018 ISS) Toll-like Receptor 9 (TLR9) agonist 20 µg HBsAg mixed with 3000 µg 1018 ISS Administered in 2 doses on 0,1 month schedule |
 TLR Overview TLR3 TLR7 TLR8 TLR9 TLR1 TLR2 TLR4 TLR5 TLR6 TLR10 TLR2 ssRNA CpG DNA (ISS) dsRNA ssRNA Endosome Cytosol Diacyl lipopeptides Triacyl lipopeptides LPS Flagellin ? 4 of these TLR recognize nucleic acids TIRAP MyD88 TIRAP MyD88 MyD88 TIRAP TRAM TRIF MyD88 MyD88 MyD88 MyD88 TRIF MyD88 |
 HBV-16: Study Design Healthy adults, 40 to 70 years of age Two doses of HEPLISAV (0, 4 weeks) + 1 dose placebo (24 weeks) compared to 3 doses of Engerix-B (0, 4, 24 weeks) Immunogenicity assessed by Ortho Vitros ECi assay Seroprotection defined as anti-HBsAg 10 miU/ml Randomization – HEPLISAV to Engerix-B 4:1 Randomization stratified by age, by site (ages 40 to 49 years, 50 to 59 years, 60 years and over) SEAC and DSMB oversight 3793 screened, 2452 randomized, 2449 treated, 2269 completed all visits |
 HBV-16: Visit Schedule Week 0 Week 4 Week 8 Week 12 Week 18 Week 24 Week 28 Week 36 Week 44 Week 52 Screen and Randomize Active Active Placebo Active Active Active Injection Period Follow-up Period HEPLISAV ENGERIX-B Week 32 |
 HBV-16: Objectives - Immunogenicity Primary Demonstrate non-inferiority to Engerix-B at 8 weeks after the last injection (week 12 for HEPLISAV vs. week 32 for Engerix-B) Non-inferiority (week 12 HEPLISAV vs. week 32 Engerix-B) HEPLISAV will be considered non-inferior to Engerix-B if the lower limit of the 95% confidence interval of the difference in seroprotection rates (SPR) (HEPLISAV SPR for the 3 new lots combined minus the Engerix-B SPR) is greater than -10%. Superiority (week 12 HEPLISAV vs. week 32 Engerix-B) If HEPLISAV is found to be non-inferior, then and only then will it be declared to be superior if the lower limit of this 95% confidence interval is greater than zero |
 HBV-16: Seroprotection Rates (Primary Endpoint) 0% 25% 50% 75% 100% Baseline 4 8 12 18 24 28 32 36 44 52 Weeks HEPLISAV Engerix-B Engerix-B Injections HEPLISAV Injections Non-inferiority Per-Protocol Population Primary Endpoint % Difference in SPR at 8 weeks after last active dose: 19.6% (95% CI 14.7%, 24.7%) (N=1123 for HEPLISAV, 359 for Engerix-B) 90% 70.5% 95% 73% 92% 59% |
 HBV-16: Anti-HBsAg Geometric Mean Concentration 1 10 100 1000 Baseline 4 8 12 18 24 28 32 36 44 52 Weeks HEPLISAV Engerix-B Engerix-B Injections HEPLISAV Injections Non-inferiority Per-Protocol Population |
 HBV-16 Anti-HBsAg Geometric Mean Concentration: HEPLISAV Lot Consistency (Primary Endpoint) 1 10 100 1000 Baseline 4 8 12 18 24 28 32 36 44 52 Lot 8 Lot 9 Lot 10 Engerix-B HEPLISAV Engerix-B Primary Endpoint (N= 428 for Lot 8; 438 for Lot 9; 424 for Lot 10) |
 Upper bound Lower bound Consistency Criteria HBV-16: Ratio of GMCs for Lot Consistency Adjusted Ratios Lot 10/Lot 8 Lot 10/Lot 9 Lot 8/Lot 9 |
 HBV-16: Results - Safety Post Injection Reactions Incidence similar in HEPLISAV (51.0%) vs. Engerix (49.4%) Severe reactions were uncommon and slightly lower in HEPLISAV (2.8% vs. 4.2%) Pain was more frequent in HEPLISAV (34.8% vs. 31.8%) Systemic post immunization reactions were less frequent in HEPLISAV (33.4% vs. 34.7%) Incidence decreased with subsequent injections AEs Subjects experiencing at least 1 AE; HEPLISAV (50.5%) vs. Engerix-B (53.0%) - most common was nasopharyngitis (4.0% vs. 5.2%) Most AEs were mild to moderate in intensity – severe AEs (4.5% vs. 5.4%) AEs considered by PI to be treatment related (7.2% vs. 6.0%) – most common was injection site erythema (1.5% vs. 0.8%) |
 HBV-16: Results - Safety SAEs 123 SAEs reported in 99 subjects – 3.4% of subjects in HEPLISAV vs. 4.8% in Engerix-B Most common was in SOC of Musculoskeletal and Connective Tissue (1.1% HEPLISAV vs. 1.0% Engerix-B) 1 SAE was considered by PI to be treatment related – bronchial hyper-reactivity after 3rd injection (Engerix-B) 2 deaths – pulmonary embolism (HEPLISAV) and myocardial infarction (Engerix-B) AIAEs 3 new onset autoimmune adverse events occurred during the trial 2 cases of hypothyroidism and 1 case of vitiligo all were in the HEPLISAV group (3/1968 vs 0/481, P=1.00) |
 HBV-16: Conclusions In healthy adults aged 40 to 70 years: HEPLISAV provided superior peak seroprotection with fewer doses than Engerix-B HEPLISAV provided earlier seroprotection compared to Engerix-B HEPLISAV provided superior duration of seroprotection with fewer doses than Engerix-B The clinical consistency of HEPLISAV was demonstrated The safety profile of HEPLISAV was similar to Engerix-B |
 The HBV-16 Study Team Site Principle Investigators Michael Kyle Joe Blumenau Matthew Davis Martin Kabongo Reinaldo Tirado-Bernardini Dennis O’Keefe Tami Helmer Donald Sislen Ben Lasko Nancy Campbell Lunde Canas William Jennings Stephan Sharp Duane Wombolt Randle Middleton Eric Ross Maureen Ziboh Eugene DuBoff John Ervin Daniel Brune Michael Noss Martin Throne Harry Geisberg Keith Reisinger Mahashweta Ghosh William Travis Ellison John Murray, Jr. Gerasimos Zaharatos Dynavax HBV-16 Team Elizabeth Fung Liezl Boehnlein Kim Erby Lani Ibarra Connie Louis-Tse JoAnn Dyangko Stacy Maryannis Tanya Cope Elsa Guzman-Bonilla Leslie de la Cruz Hamid Namini Fang Xie Dr. Jeff Enejosa Dr. Sean Bennett Dr. William L. Heyward Dr. J. Tyler Martin Clinical Research Organizations Axio, Inc. Accelovance, Inc. Parexel, Inc. BARC USA Almac-US |