Rhein Biotech GmbH A Dynavax Technologies …...E&Y Life Science Mtg, Düsseldorf, May 11, 2011...

E&Y Life Science Mtg, Düsseldorf, May 11, 2011

Rhein Biotech GmbHA Dynavax Technologies Company

Wandel der Geschäftsmodelle um eine stabile Technologieplattform

Dr. Albrecht Läufer – Head Business Development

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.

Dynavax: Company Profile

1996 - Incorporated

1998 – Fully operational

Headquarters Berkeley, CA

2004 – IPO

NASDAQ: DVAX

2006 – Acquired Rhein Biotech

2010 – Fully-integrated

~150 employees worldwide

Well-capitalized; raised $90MM in public markets and equity line of credit for $30MM

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 2011- 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

Dynavax‘s Pipeline

Asthma / COPDAsthma / COPD

Universal Flu VaccineUniversal Flu Vaccine

Autoimmunity / InflammationAutoimmunity / Inflammation

Phase IIIPhase IIPhase IPreclinical

Hepatitis B TherapyHepatitis B Therapy

Hepatitis C TherapyHepatitis C Therapy

HEPLISAVTM Hepatitis B VaccineHEPLISAVTM Hepatitis B Vaccine

■ 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

ISSAdjuvant

Faster and stronger immune response

ISS Technology – Toll-Like Receptor 9 Agonists

Three presentation forms:

+ ISS ISS

e.g. Heplisav e.g. NP-Flu

ISS

e.g. Asthma

ISS ISSISSISS

ISS

■ Sequenced Genome■ Safe host strain (GRAS)■ Growth up to 45°C @ pH 2.5 – 6.0■ Multi-copy integration of foreign DNA, 40 – 60 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

Hansenula polymorpha protein productionplatform

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 largestselling worldwide■ Pentavalent vaccine (DTwP/Hib/HepB)■ Other combination vaccines■ INF α■ Hirudin■ Insulin■ Industrial Enzymes

Berkeley & Düsseldorf

■ Drug discoveryTLR 9 agonists (ISS) and TLR inhibitors

■ Pre-clinical developmentAnimal models, immunologyTox

■ Clinical developmentINDs / Phase I - III

■ RegulatoryFDA, EMEA

■ IP

■ Pre-clinical developmentMolecular biology

- Strain constructionImmunology

- Mice & clinicalVaccines

- Novel adjuvants- Antigen presentation, VLPs

■ Process developmentAnalytical Up-stream, down-streamFormulation development

■ ManufacturingEU GMP, FDA compliantQPClinical and Commercial lots

■ IP

Berkeley Düsseldorf

A perfect fit

Rhein Biotech History I

Technologies & Product Development

H.polymorpha Technology

Hepatitis B Vaccine Technology

Product Development Manufacturing Sales

Vaccines Immunomodulators

1985 1999/2000 2002

Rhein Biotech GmbH Germany


Rhein Biotech N.V. The Netherlands

Green Cross Vaccines Korea

Rhein Americana SA Argentina

Berna Biotech AGSwitzerland

Rhein Biotech N.V.The Netherlands

Product Development Manufacturing Sales

Vaccines Immunomodulators



Rhein Americana SA Argentina

Rhein Biotech History II

Drug Discovery ISS Technology Platform

Phase 3 HEPLISAVTM Hepatitis B Vaccine Phase 2 Tolamba Allergy VaccinePhase 1 Universal Flu VaccinePhase 1 Hepatitis C VaccinePhase 1 Hepatitis B Immunotherapeutic

Manufacturing

2006 2010

Dynavax Technologies Corporation, USA


Berna Biotech AGSwitzerland

Crucel N.V. The Netherlands

Rhein Biotech N.V.The Netherlands


Product Development Manufacturing Marketing

VaccinesAntibodies


Some highlights

■ WHO pre-qualified supplier

■ 1996 - 2002 Member of Rhein Biotech Group

■ 2002 Berna Biotech & Crucell

GreenCross VaccineCorporation, Korea

Crucell N.V., The Netherlands

Rhein Americana S.A.Argentina

Aventis Pasteur

Serum Institute of India

■ 1996 – 2001 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

Rhein Biotech – Two Business Areas

ProductDevelopment Manufacturing&

100 % subsidiary of Dynavax Technologies, Berkeley / USA with a separate Supervisory Board

Own Projects Own Projects3rd party service and

collaboration

3rd party service and

collaboration

■ Increased, rapid protection (2-dose)■ Durable antibody levels■ Improved compliance through convenient

vaccination regimen

■ Clinical data from over 4,000 subjects

■ Phase 3 PHAST trial completed in adults 18-55 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

■ 2 final registration trials (>2.000 patients) currently running to support licensure in U.S. and Europe

HEPLISAVTM

Phase III Hepatitis B Vaccine

AdjuvantISS TLR 9 agonist

Antigen HBsAg

HeplisavVaccine

Rhein Biotech, DE Dynavax, US

Alum-free

97%92%

97%

18%

27%

17%

75%

3%0%

25%

50%

75%

100%

% S

erop

rote

ctio

n (S

PR)

(ant

i-HB

s >1

0 m

IU/m

L)

Engerix-B3 doses over 6

months

HEPLISAV2 doses

over 1 month

>75% difference

>20% difference

HEPLISAVTM

Clinical Data: Phase III - Ages 40 - 55

Current vaccines require 3 doses for full effect; compliance extremely challenging

Placebo

VS.

HEPLISAVENGERIX-B

Month 1 Month 3 Month 7Month 6

TheravaxHepatitis B Chronic Infection

■ Chronic infection (5-10%)~ 350 million chronic carriers worldwide30% progress to liver cirrhosis / hepatocellular carcinoma

■ Current treatmentIFNα > only 30 % responders; low tolerabilityAntivirals > life long treatment necessary; resistances

Unmet Medical Need

Improved therapy to achieve sustained viral control under timely limited treatment

TheravaxTherapeutic Hepatitis B Vaccine – Rationale

■ Spontaneous resolution of chronic Hepatitis B in 0.2 % of carriers1,2

■ Possible recovery from chronic Hepatitis B infection3 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, self-limiting HBV infection

■ HBcAg specific T cell response correlates with viral clearance4,5

1 Liaw et al (1991) Hepatology 13:6252 Wong et al (1993) Ann Intern Med 119:3123 Lau et al (2002) Gastroenterology 122:6144 Bertoletti et al. (2003) J Hepatology 39:1155 Thimme et al. (2003) J Virology 77:68

Chronic infection can in principle be resolved by T cell response (esp. HBcAg specific). Therapeutic Hepatitis B vaccination is feasible.

‘Theravax’ (DV-601)Composition - A Product of Three Components

AdjuvantrHBsAg particle rHBcoreAg particle

+

+ +

■ HBcore Ag included■ Broad HBV epitope spectrum■ Potent T cell adjuvant and delivery system

Hepatitis B Virus

DV-601 Composition

Key Features

Theravax Therapeutic Hepatitis B Vaccine

■ Preclinical proof of concept in transgenic animalsCD8 + T-cell response (HBsAg and HBcoreAg specific)Anti-HBsAg antibodiesElimination of HBs AntigenemiaReduction of viral load

■ Clinical Phase I in healthy volunteersVaccine is immunogenicStrong 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

■ Clinical Phase Ib in chronic patients Dose-escalating studyAll doses generally safe and well toleratedIndividual immunologic and virologic responses were observed across cohorts at all dose levels

Break of immuno-tolerance

Partner for Product Development from Bench to 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)

Preclinic Process Dev. MFG Clinic MarketIdea

Summary: Changing business models –stable technology platform

■ 1985 – 1999 technology and science driven “biotech boutique”, fantastic exit for investors (IPO ´99, and “merger” with Berna 2002).

■ 1999 – 2006 technology and science driven PLUS preclinical and clinical development, excellent products for our partners.

■ 2006 - today pharmaceutical development and manufacturing company, excellent proprietary products PLUS services for partners

strong manufacturing platform: Hansenula polymorphastrong adjuvant platform: ISS

high potential drug candidates: Heplisav, Theravax, Universal Flu, …

Contact

Rhein Biotech GmbH- Dynavax Europe -Eichsfelder Straße 1140595 Düsseldorf

Tel: +49 211 75845-183Fax: +49 211 [email protected]

Rhein Biotech GmbH A Dynavax Technologies …...E&Y Life Science Mtg, Düsseldorf, May 11, 2011...

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