Rhein Biotech GmbH A Dynavax Technologies Company Wandel der Geschäftsmodelle um eine stabile Technologieplattform

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1 Rhein Biotech GmbH A Dynavax Technologies Company Wandel der Geschäftsmodelle um eine stabile Technologieplattform Dr. Albrecht Läufer Head Business Development E&Y Life Science Mtg, Düsseldorf, May 11, 2011

2 Forward-Looking Statements This presentation contains forward-looking statements that are subject to a number of risks and uncertainties, including statements about our product candidates, clinical development plans and timelines, business plans, projected operating results and financial position. Actual results may differ materially due to the risks and uncertainties inherent in our business, including whether HEPLISAV can be further developed, financed or commercialized, or even if further development is permitted, that successful development and approval can occur in a timely manner or without significant additional studies and difficulties or delays in development; initiation and completion of pre-clinical studies and clinical trials of our other product candidates, the results of clinical trials and the impact of those results on the initiation or continuation of subsequent trials and issues arising in the regulatory process; achieving the objectives of and maintaining our collaborative and licensing agreements; the scope and validity of patent protection for our products; possible claims against us based on the patent rights of others; our ability to obtain additional financing to support our operations; and other risks detailed in the "Risk Factors" section of our current periodic reports filed with the SEC. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. Page 1

3 Dynavax: Company Profile 2010 Fully-integrated ~150 employees worldwide Well-capitalized; raised $90MM in public markets and equity line of credit for $30MM 2006 Acquired Rhein Biotech 2004 IPO NASDAQ: DVAX 1998 Fully operational Headquarters Berkeley, CA Incorporated

4 Dynavax Today HEPLISAV - positive results from two Phase 3 trials and the potential to become the Best-in-Class Hepatitis B Vaccine - Superior protection and improved convenience vs. Engerix-B - Expect to complete a Phase 3 lot-consistency and safety trial in 1H Plan to file BLA by end of 2011 Demonstrated safety in over 2,500 patients - Comparable safety profile to Engerix-B Large addressable market - > $1 billion potential market for adult hepatitis vaccines - Additional focus on low responding and high risk populations Universal Flu Vaccine in Phase I trials - Potential to protect against divergent strains, improve efficacy and reduce required dosage - Worldwide Supply and Option Agreement with Novartis TLR Inhibitors Partnered with GSK - Unique approach for autoimmune and inflammatory disease

5 Dynavax s Pipeline Preclinical Phase I Phase II Phase III HEPLISAV TM Hepatitis B Vaccine Universal Flu Vaccine Hepatitis B Therapy Hepatitis C Therapy Asthma / COPD Autoimmunity / Inflammation Page 4

6 ISS Technology Toll-Like Receptor 9 Agonists Three presentation forms: + ISS ISS ISS ISS ISS ISS ISS ISS e.g. Heplisav e.g. NP-Flu e.g. Asthma ISS = ImmunoStimulatory Oligonucleotide Sequences ISS are short, CpG-containing oligonucleotide agonists of Toll-like Receptor 9 ISS activate primarily Plasmacytoid Cells (PDC) and B cells in humans ISS are potent adjuvants for antibody and Th1 responses ISS stimulate Th1 and inhibit Th2 development ISS Adjuvant Faster and stronger immune response Page 5

7 Hansenula polymorpha protein production platform Sequenced Genome Safe host strain (GRAS) Growth up to 45 ph Multi-copy integration of foreign DNA, copies Mitotically stable integration of expression cassettes Co-expression of different foreign genes Production of virus like particles (VLPs) Secretion and intracellular expression Glycosylation without allergenic terminal 1,3-mannose Strong inducible and constitutive promoters Cultivation with inexpensive, synthetic media Endotoxine free Robust system for recombinant protein expression Page 6

8 Track Record Partnerships, Collaborations and Services Collaborations/Services SK (GSK) Ciba Geigy (Novartis) DuPont Hoechst AG (Aventis) BASF/Knoll AG - Abbott Bayer Vakzine Project Management Danisco Merck BioVascular Innogenetics (Solvay Pharmaceuticals) Crucell Medigen Roche Diagnostics Heineken Bio Merieux Diasorin Eurogentec Boehringer Ingelheim Partnerships, Joint Ventures, Technology Transfer Aventis Pasteur (Sanofi Aventis), France GCVC, Korea (Crucell N.V., The Netherlands) Wockhardt Rhein Biopharm, India Rhein Minapharm, Egypt Rhein Americana, Argentina Serum Institute of India Mubio Products, The Netherlands Developed/Licensed Out and Marketed: 3 dose Hepatitis B vaccine >> third largest selling worldwide Pentavalent vaccine (DTwP/Hib/HepB) Other combination vaccines INF α Hirudin Insulin Industrial Enzymes Page 7

9 Berkeley & Düsseldorf Drug discovery TLR 9 agonists (ISS) and TLR inhibitors Pre-clinical development Animal models, immunology Tox Clinical development Regulatory IP Berkeley INDs / Phase I - III FDA, EMEA Pre-clinical development Molecular biology - Strain construction Immunology - Mice & clinical Vaccines - Novel adjuvants - Antigen presentation, VLPs Process development Analytical Up-stream, down-stream Formulation development Manufacturing IP Düsseldorf EU GMP, FDA compliant QP Clinical and Commercial lots A perfect fit Page 8

10 Rhein Biotech History I Rhein Biotech GmbH Germany Rhein Biotech N.V. The Netherlands Berna Biotech AG Switzerland Rhein Biotech GmbH Germany Rhein Biotech N.V. The Netherlands Green Cross Vaccines Korea Rhein Americana SA Argentina Rhein Biotech GmbH Germany Green Cross Vaccines Korea Rhein Americana SA Argentina / Technologies & Product Development H.polymorpha Technology Hepatitis B Vaccine Technology Product Development Manufacturing Sales Vaccines Immunomodulators Product Development Manufacturing Sales Vaccines Immunomodulators Page 9

11 Rhein Biotech History II Crucel N.V. The Netherlands Berna Biotech AG Switzerland Rhein Biotech N.V. The Netherlands Rhein Biotech GmbH Germany Dynavax Technologies Corporation, USA Rhein Biotech GmbH Germany Green Cross Vaccines Korea Product Development Manufacturing Marketing Vaccines Antibodies Drug Discovery ISS Technology Platform Phase 3 HEPLISAV TM Hepatitis B Vaccine Phase 2 Tolamba Allergy Vaccine Phase 1 Universal Flu Vaccine Phase 1 Hepatitis C Vaccine Phase 1 Hepatitis B Immunotherapeutic Manufacturing Page 10

12 Some highlights GreenCross Vaccine Corporation, Korea Crucell N.V., The Netherlands Rhein Americana S.A. Argentina Aventis Pasteur Serum Institute of India WHO pre-qualified supplier Member of Rhein Biotech Group 2002 Berna Biotech & Crucell Joint Venture of Rhein Biotech Group 1999 technology transfer HBsAg Production facility was sold to Aventis Pasteur WHO pre-qualified supplier Since 1997 Licensee of Rhein Biotech Group 1997 technology transfer HBsAg Page 11

13 Rhein Biotech Two Business Areas Product Development & Manufacturing Own Projects 3rd party service and collaboration Own Projects 3rd party service and collaboration 100 % subsidiary of Dynavax Technologies, Berkeley / USA with a separate Supervisory Board Page 12

14 HEPLISAV TM Phase III Hepatitis B Vaccine Increased, rapid protection (2-dose) Durable antibody levels Improved compliance through convenient vaccination regimen Rhein Biotech, DE Antigen HBsAg Dynavax, US Adjuvant ISS TLR 9 agonist Clinical data from over 4,000 subjects Phase 3 PHAST trial completed in adults years of age Phase 3 trial completed in adults > 40 years of age Total of 9 clinical studies completed to date, including studies in chronic kidney disease patients Heplisav Vaccine 2 final registration trials (>2.000 patients) currently running to support licensure in U.S. and Europe Alum-free Page 13

15 HEPLISAV TM Clinical Data: Phase III - Ages % Seroprotection (SPR) (anti-hbs >10 miu/ml) 100% 75% 50% 25% 0% 18% 3% 92% >75% difference 17% 97% 27% Placebo 97% >20% difference 75% HEPLISAV ENGERIX-B Month 1 Month 3 Month 6 Month 7 HEPLISAV 2 doses over 1 month VS. Engerix-B 3 doses over 6 months Current vaccines require 3 doses for full effect; compliance extremely challenging Page 14

16 Theravax Hepatitis B Chronic Infection Chronic infection (5-10%) ~ 350 million chronic carriers worldwide 30% progress to liver cirrhosis / hepatocellular carcinoma Current treatment IFNα > only 30 % responders; low tolerability Antivirals > life long treatment necessary; resistances Unmet Medical Need Improved therapy to achieve sustained viral control under timely limited treatment Page 15

17 Theravax Therapeutic Hepatitis B Vaccine Rationale Spontaneous resolution of chronic Hepatitis B in 0.2 % of carriers 1,2 Possible recovery from chronic Hepatitis B infection 3 by transplantation of bone marrow from donors with natural immunity to HBV HBV specific T cell responses undetectable (much weaker) in chronic infection compared to vigorous immune response during acute, selflimiting HBV infection HBcAg specific T cell response correlates with viral clearance 4,5 Chronic infection can in principle be resolved by T cell response (esp. HBcAg specific). Therapeutic Hepatitis B vaccination is feasible. 1 Liaw et al (1991) Hepatology 13:625 2 Wong et al (1993) Ann Intern Med 119:312 3 Lau et al (2002) Gastroenterology 122:614 4 Bertoletti et al. (2003) J Hepatology 39:115 5 Thimme et al. (2003) J Virology 77:68 Page 16

18 Theravax (DV-601) Composition - A Product of Three Components Hepatitis B Virus + DV-601 Composition + + rhbsag particle rhbcoreag particle Adjuvant Key Features HBcore Ag included Broad HBV epitope spectrum Potent T cell adjuvant and delivery system Page 17

19 Theravax Therapeutic Hepatitis B Vaccine Preclinical proof of concept in transgenic animals CD8 + T-cell response (HBsAg and HBcoreAg specific) Anti-HBsAg antibodies Elimination of HBs Antigenemia Reduction of viral load Clinical Phase I in healthy volunteers Vaccine is immunogenic Strong T cell responses (CD8 and CD4) against HBcAg and HBsAg (equal or higher than corresponding responses in acute resolved patients) High anti-hbs antibody titers Break of immuno-tolerance Clinical Phase Ib in chronic patients Dose-escalating study All doses generally safe and well tolerated Individual immunologic and virologic responses were observed across cohorts at all dose levels Page 18

20 Partner for Product Development from Bench to Market Idea Preclinic Process Dev. MFG Clinic Market Strain Development (yeast, E. coli, mammalian and insect cells) Immunology / Biomarkers / Adjuvants Preclinical Efficacy and Safety Analytical Development Process Development / Optimization Manufacturing (EU-GMP), FDA compliant Quality Management (GLP, GMP) Quality Control, release of API and Drug Products Clinical Development Support Regulatory Support (German National authorities, EMA, US-FDA) Page 19

21 Summary: Changing business models stable technology platform technology and science driven biotech boutique, fantastic exit for investors (IPO 99, and merger with Berna 2002) technology and science driven PLUS preclinical and clinical development, excellent products for our partners today pharmaceutical development and manufacturing company, excellent proprietary products PLUS services for partners strong manufacturing platform: Hansenula polymorpha strong adjuvant platform: ISS high potential drug candidates: Heplisav, Theravax, Universal Flu, Page 20

22 Contact Rhein Biotech GmbH - Dynavax Europe - Eichsfelder Straße Düsseldorf Tel: Fax: alaeufer@eu-dynavax.com Page 21