Development of Recombinant MERS-CoV Spike (S) Nanoparticle Vaccine Russell P. Wilson Senior Vice President, Business Development Vaccine World MENA & CIS 2014 Istanbul, Turkey November 19, 2014 1 www.novavax.com
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Discussion Topics Brief overview of Novavax The MERS threat Novavax MERS-CoV Spike (S) Vaccine Two recent case studies of other emerging infectious diseases (H7N9 & Ebola) Closing remarks 3
Novavax Overview Recombinant Nanoparticle Vaccine Technology: Innovative, proprietary technology to produce vaccine candidates that efficiently and effectively respond to both well-known and emerging diseases. Later-Stage Development Programs: RSV Vaccine Only later-stage RSV vaccine candidate in the clinic Seasonal Flu Novel recombinant vaccine Pandemic Flu Novel H7N9 recombinant vaccine Breakthrough Clinical Data: RSV Vaccine: Induces immune response activity similar to marketed monoclonal antibody used for pre-term infants (Synagis ) Pandemic influenza vaccines: H5N1 flu vaccine: induced robust and cross-reactive immunogenicity H7N9 flu vaccine: first positive clinical data, published in the New England Journal of Medicine Supported by U.S. government (HHS-BARDA) development contract for up to $179 MM Strong Vaccine Development Infrastructure Experienced management team (>200 years of vaccine experience) Strong balance sheet (over $190 MM in cash as of 30Sep2014) Manufacturing capacity for both antigen and adjuvant capacity 4
Protein Production Using Baculovirus Expression System Genetic sequences encoding vaccine antigens selected Genes cloned into baculovirus Baculovirus infects insect cells (Sf9) Antigens expressed and purified Clone genes into baculovirus Infect Sf9 insect cells with baculovirus Sf9 cells express protein antigens Product 5
Product Pipeline: Current Program RSV Infants (Maternal Immunization) Elderly Pediatrics (6 mos 6 yrs) Influenza Seasonal Pandemic (H7N9+Matrix-M ) Pandemic (H5N1) New Vaccines Ebola MERS Collaborators Preclinical Phase 1 Phase 2 Phase 3 Rabies (@ Indian JV) 6
A Leading Vaccine Development Company with a Global Reach Novavax AB Uppsala, SWEDEN Novavax Maryland, USA 7
Significant Manufacturing Infrastructure in Place R&D facility, including GMP pilot plant to manufacture Phase 1 & 2 trial materials in U.S. GMP manufacturing facility for Phase 3 and commercial launch in U.S. GMP adjuvant manufacturing facility for clinical and commercial production in Sweden 8
9 The MERS Threat
10 MERS Cases Beyond the KSA
Middle East Respiratory Syndrome (MERS) Coronavirus (CoV) Spike (S) glycoprotein o o receptor binding fusion Membrane (M) glycoprotein o Membrane spanning MERS-CoV Re-emerging Disease 11
Saudi Sequence of Novavax MERS-CoV Published June 10, 2013 MERS CoV Isolate Al-Hasa_1_2013 Sequence submitted by the Ministry of Health, Kingdom of Saudi Arabia 12
Novavax MERS-CoV Al-Hasa_1_2013 Nanoparticle Vaccine Recombinant baculovirus full length, codon optimized MERS S Manufacturing in Sf9 insect cells followed by chromatography purification Self-assembly of MERS S trimers: 26nm proteinprotein micelles 13
Preclinical Testing of Novavax MERS-CoV Spike (S) Vaccine Vaccine 32 (2014) 3169-3174 Novavax MERS-CoV Al-Hasa_1_2013 Nanoparticle Vaccine Induced Neutralizing Antibodies Novavax vaccine platform can be used to induce a neutralizing antibody response in mice for both MERS and SARS Matrix-M adjuvant significantly enhances the level of neutralizing antibody produced compared to Alum 14
Two Recent Case Studies Novavax Response to Other Emerging Infectious Diseases H7N9 pandemic influenza strain First recognized by Chinese health authorities as a potential pandemic influenza threat in late March 2013. In a three-month period, Novavax developed a vaccine antigen, conducted multiple animal studies and initiated the world s first Phase 1 clinical trial of a vaccine against an H7N9 influenza strain. Clinical results published in November 2013 in The New England Journal of Medicine - achieved protective levels from vaccinations within just 116 days of the announcement of the H7N9 outbreak. Ebola Cloned the current Guinea strain of Ebola now circulating in West Africa after gene sequence published in the journal Science in September 2014 First, and currently only, reported Ebola vaccine produced using the genetic sequence of the Guinea strain. Successfully tested vaccine in both rodent and rabbit pre-clinical models. Initiated non-human primate study Manufactured initial clinical material and expect to initiate a Phase 1 clinical trial soon 15
Flexible, Rapid and Proven Vaccine Technology Timeline for Novavax H7N9 Response Animal efficacy data GMP manufacture First human doses administered 08 July 2013 16 16
Adjuvanted Vaccine Provides Protection Before the Second Wave Protective levels achieved within just 116 days of the announcement of the H7N9 outbreak. Chinese publish genetic sequence of H7N9 Novavax initiates A(H7N9) vaccine development Novavax A(H7N9) vaccine administered to humans Potential protective responses present in subject sera 17
H7N9 = Poor Immunogen and Requires Adjuvant % = seroconversion rates 80.6% 64.9% 64.8% 36.8% 15.9% Potential for Dose-Sparing 5.7% Trial Design: Randomized, observerblind, saline placebocontrolled (n=40/group) Two identical doses at Days 0 and 21, with and without saponin-based adjuvant (Iscomatrix ) Key serology time points: Days 0, 21 and 35, with later follow-up to assess antibody persistence 18
Adjuvant Demonstrates Strong Cross Clade Responses Data from H5N1 Study HAI Titers of A/Vietnam/1203/04 (clade 1) to A/Indonesia/5/05 Vaccine 45µg HA 15µg HA 15µg HA 7.5µg HA 3.75µg HA Placebo Adjuvant No No Yes Yes Yes No SCR 54.2 (40.1) 24.5 (12.4) 79.6 (68.9) 76.0 (64.2) 73.3 (60.4) 2.1 (0) % 40 54.2 (40.1) 34.7 (21.4) 81.5 (71.1) 78.0 (66.5) 80.0 (68.3) 4.3 (0) GMR 4.2 (3.0) 2.2 (1.6) 8.8 (6.6) 7.5 (5.5) 8.5 (6.1) 1.0 (0.8) ( ) = Lower 95% CI = fulfillment of CBER criteria at lower 95% confidence bound = fulfillment of CBER criteria at point estimate 19
Ebola Case Study: Novavax EBOV Glycoprotein (GP) Nanoparticle Vaccine EBOV GP based on the Guinea, cluster 3 gene sequence; Gire, et al Science;12 September 2014 Full length, unmodified EBOV GP 1,2 [H.sapiens -wt/sle/2014/ ManoRiver-G3798; cluster 3] Clone genes into baculovirus Infect Sf9 insect cells with baculovirus Sf9 cells express protein antigens EBOV GP 20
Novavax Guinea Ebola GP Sequence Comparison: Mayinga 1976 vs Guinea 2014 1976 GP 2014 GP: 20 AA mutations mab 13F6 Gire, et al, Science 12 Sept 2014 Lee et al, Nature 2008 21
Preclinical Immunogenicity Study in Mice of Recombinant 2014 EBOV GP Vaccine STUDY DESIGN: Group N EBOLA Vaccine GP Dose (µg) Adjuvant (µg) Immun days Blood Draw days 1 10 5-0, 14 0, 21, 28 2 10 5 Matrix M (5) 0, 14 0, 21, 28 3 10 5 Al PO 4 (50) 0, 14 0, 21, 28 4 10 Saline - - 0, 21, 28 22
23 2014 Recombinant EBOV GP Vaccine Anti-GP ELISA (EC90) Responses in Mice
PsVNA50 Cross-Neutralization 2014 (Guinea) EBOV GP Vaccine of 1976 (Mayinga) PsVNA50 Pseudovirus 1 10 5 10 4 10 3 10 2 1 Jay Hooper, USAMRIID neutralization assay PSVNA50 24
Next Steps with Novavax EBOV GP Vaccine Initiated non-human primate study Manufactured initial clinical material and expect to initiate a Phase 1 clinical trial soon Subsequent clinical studies will be designed following the data from the non-human primate study and the Phase 1 clinical trial. 25
Novavax Technology = Potential Platform of Choice to Address Emerging Infectious Disease Threats Recombinant system allows for quick antigen selection Proceed from gene to human clinical data in comparatively short periods of time (e.g., MERS, Ebola, H7N9) Recombinant system allows for better match of vaccine strains to wildtype virus may improve vaccine effectiveness Single-use technology Fast responder - flexible, agile Standardized process Reproducible clinical results Novavax vaccines tested in > 7,000 subjects (e.g., RSV, seasonal influenza, and H7N9, H5N1, H1N1 pandemic influenza vaccines) Effective dose-sparing capability Matrix-M (saponin-based) adjuvant demonstrated dose-sparing capability of platform Cross-protection Matrix-M adjuvant may broaden the scope of protection (e.g., cross-strain protection) as pathogens change and mutate 26
Potential Future Directions for a MERS Vaccine Immunize humans Middle Eastern health care workers and first responders Pilgrims to Saudi Arabia General populace Immunize camels Generation of therapeutic antibodies for treatment of ill patients 27
Thank you! 28 www.novavax.com