Development of Recombinant MERS-CoV Spike (S) Nanoparticle Vaccine

Transcription

1 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,

2 Safe Harbor Statement Statements herein relating to future financial or business performance, conditions or strategies and other financial and business matters, including expectations regarding clinical development, product sales, operating expenses, and anticipated milestones are forward-looking statements within the meaning of the Private Securities Litigation Reform Act. Novavax cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Such factors that may cause actual results to differ materially from the results discussed in the forward-looking statements or historical experience include risks relating to the early stage of Novavax s product candidates under development; current results may not be predictive of future pandemic results, results of our seasonal influenza vaccine or any other vaccine that we may develop; further testing is required before regulatory approval can be applied for and the FDA may not approve a vaccine even if further trial results are similar to those disclosed previously by the company; uncertainties relating to clinical trials, including possible delays in initiating or completing the trials and safety and efficacy results; dependence on the efforts of third parties; competition for clinical resources and patient enrollment from drug candidates in development by other companies with greater resources and visibility; and risks that we may lack the financial resources and access to capital to fund our operations including further clinical trials. Further information on the factors and risks that could affect Novavax s business, financial conditions and results of operations, is contained in Novavax s filings with the U.S. Securities and Exchange Commission, which are available at These forward-looking statements speak only as of the date of this presentation, and Novavax assumes no duty to update forward-looking statements. 2

3 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

4 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

5 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

6 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

7 A Leading Vaccine Development Company with a Global Reach Novavax AB Uppsala, SWEDEN Novavax Maryland, USA 7

8 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 9 The MERS Threat

10 10 MERS Cases Beyond the KSA

11 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

12 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

13 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

14 Preclinical Testing of Novavax MERS-CoV Spike (S) Vaccine Vaccine 32 (2014) 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

15 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 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

16 Flexible, Rapid and Proven Vaccine Technology Timeline for Novavax H7N9 Response Animal efficacy data GMP manufacture First human doses administered 08 July

17 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

18 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

19 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) % (40.1) 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

20 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

21 Novavax Guinea Ebola GP Sequence Comparison: Mayinga 1976 vs Guinea GP 2014 GP: 20 AA mutations mab 13F6 Gire, et al, Science 12 Sept 2014 Lee et al, Nature

22 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 , 14 0, 21, Matrix M (5) 0, 14 0, 21, Al PO 4 (50) 0, 14 0, 21, Saline - - 0, 21, 28 22

23 Recombinant EBOV GP Vaccine Anti-GP ELISA (EC90) Responses in Mice

24 PsVNA50 Cross-Neutralization 2014 (Guinea) EBOV GP Vaccine of 1976 (Mayinga) PsVNA50 Pseudovirus Jay Hooper, USAMRIID neutralization assay PSVNA50 24

25 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

26 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

27 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

28 Thank you! 28