Slide 1: Update on Novavax Investigational NanoFlu Vaccine and COVID-19-Influenza Combination Vaccine Development
1 © 2022 NOVAVAX. All rights reserved. UPDATE ON NOVAVAX INVESTIGATIONAL N anoFlu VACCINE AND COVID - 19 - INFLUENZA COMBINATION VACCINE DEVELOPMENT VIVEK SHINDE, MD APRIL 20, 2022 | NOVAVAX
Slide 2: Safe Harbor Statement
SAFE HARBOR STATEMENT 2 © 2022 NOVAVAX. All rights reserved. Certain information, particularly information relating to the future of Novavax, its operating plans and prospects, its partnerships, the ongoing development of NVX - CoV 2373 , including Novavax’ plans to initiate a pediatric study in Q 2
Slide 3: Overview
OVERVIEW NanoFlu ( qNIV ) Vaccine Program Development COVID - Influenza Combination (CIC) Vaccine Development 3 © 2022 NOVAVAX. All rights reserved.
Slide 4: NanoFlu (qNIV) Vaccine Development
N anoFlu * ( q NIV ) VACCINE DEVELOPMENT 4 © 2022 NOVAVAX. All rights reserved. * NanoFlu identifies a recombinant hemagglutinin (HA) protein nanoparticle influenza vaccine candidate produced by Novavax. This investigational candidate was evaluated during a controlled phase 3 trial conducted during
Slide 5: Characteristics of Currently Licensed Influenza Vaccines
Characteristics Addressed VACCINE TYPE EGG - ADAPTIVE CHANGES ANTIGENIC DRIFT IMMUNOSENESCENCE ANTIBODIES T - CELLS Standard Inactivated 1,2,3,4,5 High - dose inactivated 1,3,4,5 x MF - 59 Adjuvanted 4,5,6,7 x x ? Cell - derived inactivated 5,8 ? Recombinant 2,3,4 x x x NanoFlu ( qNIV ) 9,10 [recomb
Slide 6: 6 © 2022 NOVAVAX. All rights reserved.
6 © 2022 NOVAVAX. All rights reserved.
Slide 7: Phase 3: A Non-Inferiority Immunogenicity Trial
AIMS • Demonstrate immunologic non - inferiority to licensed influenza vaccine ( Fluzone Quadrivalent) on 4 homologous strains • Establish pivotal clinical trial dataset to support filing of BLA via accelerated approval path PHASE 3: A NON - INFERIORITY IMMUNOGENICITY TRIAL Primary objectives: • Dem
Slide 8: Phase 3 Summary: Primary Endpoint Met
• Primary immunogenicity endpoint met on all homologous strains assessed with egg - adapted HAI antibody responses • GMT ratio and seroconversion difference success criteria met for non - inferiority • NanoFlu : 24 — 66% higher wild - type HAI antibody responses vs Fluzone quadrivalent against 4 hom
Slide 9: Phase 3 CMI: Potent Induction of Polyfunctional CD4+ T Cell Responses
PHASE 3 CMI: POTENT INDUCTION OF POLYFUNCTIONAL CD4+ T CELL RESPONSES RCD plot of Day 0 and 7 counts of double cytokine+ effector CD4+ T cells against A/Kansas (H3N2) 9 © 2022 NOVAVAX. All rights reserved. • qNIV right shifted distribution • Virtually all qNIV participants became “ CMI responders ,”
Slide 10: Phase 3 CMI: Kinetics of Effector CD4+ T Cell Responses Over 1 Year
Day 7, 28, 364 geometric mean fold rise (GMFRs) relative to Day 0, of double cytokine+ effector CD4+ T cells against A/Kansas (H3N2), B/ Marylan (B - Vic), A/Cambodia (drifted H3N2), or A/Wisconsin (drifted H1N1) 10 © 2022 NOVAVAX. All rights reserved. PHASE 3 CMI: KINETICS OF EFFECTOR CD4+ T CELL R
Slide 11: Phase 3: Summary and Conclusions
PHASE 3: SUMMARY AND CONCLUSIONS Primary endpoint met: • Demonstrated immunologic non - inferiority to Fluzone Quad (egg - adapted HAI antibody responses) Statistically significant higher wild - type HAI antibody responses compared to Fluzone Quadrivalent: • 24 — 66% improved Day 28 GMTs against hom
Slide 12: COVID-Influenza Combination (CIC) Vaccine Development
COVID - INFLUENZA COMBINATION (CIC) VACCINE DEVELOPMENT 12 © 2022 NOVAVAX. All rights reserved.
Slide 13: Rationale for a COVID-Influenza Combination Vaccine
RATIONALE FOR A COVID - INFLUENZA COMBINATION VACCINE RECURRENT BOOSTERS OF A SARS - COV - 2 VACCINE MAY BE NEEDED IN FUTURE Ongoing potential for emergence of variants escaping natural/vaccine immunity Continued SARS - CoV - 2 circulation , potentially in a seasonally recurrent pattern Waning of ne
Slide 14: Novel Dose Finding Study Design Using Design of Experiments Approach
The study will evaluate dose ranges for both Spike and Hemagglutinin antigens, using a Design of experiments (DoE) approach with 14 treatments groups Key antibody and cell - mediated immunity responses will be used to select one or more doses to advance into further development Participants are admi
Slide 15: Phase I/II Study Design
640 adults aged 50 – 70 years , seropositive by infection or vaccination ≥ 8 week prior 2 doses of various CIC formulations, 56 days apart rS dose range 2.5 - 22.5 μ g/dose HA dose range 5 - 60 μ g/strain/dose Matrix - M adjuvant dose : 50 μ g/dose Safety and reactogenicity: through Day 70 and 182 I
Slide 16: Preliminary Results of Phase 1/2 CIC Vaccine Trial
16 PRELIMINARY RESULTS OF PHASE 1/2 CIC VACCINE TRIAL © 2022 NOVAVAX. All rights reserved.
Slide 17: Baseline Characteristics, Reactogenicity and Safety Results
BASELINE CHARACTERISTICS, REACTOGENICITY AND SAFETY RESULTS 17 © 2022 NOVAVAX. All rights reserved. Treatment groups were comparable at baseline • Median age 59 years • 62% male / 38% female • 100% had received prior primary series EUA COVID - 19 vaccine; median 10.7 weeks prior to Day 0 • ~0.2% had
Slide 18: Anti-S IgG Dose Response with Increasing rS Dose
18 © 2022 NOVAVAX. All rights reserved. 1,000 10,000 100,000 Day 0 28 HA 0 μ g (Ref) 1,000 10,000 100,000 Day 0 28 HA 60 μ g 1,000 10,000 100,000 Day 0 28 HA 35 μ g 1,000 10,000 100,000 Day 0 28 HA 10 μ g 1,000 10,000 100,000 Day 0 28 HA 5 μ g rS 22.5 μ g rS 2.5 μ g rS 7.5 μ g rS 5.0 μ g ANTI - S Ig
Slide 19: Peak Influenza HAI Antibody Dose Response - A/Brisbane H1N1
PEAK INFLUENZA HAI ANTIBODY DOSE RESPONSE WITH INTERMEDIATE LEVELS OF HA DOSE Hemagglutination inhibition (HAI) antibody geometric mean titers (GMT) by dose and visit – A/Brisbane H1N1 19 © 2022 NOVAVAX. All rights reserved. 20 200 Day 0 28 HA 60 μ g (Ref) 20 200 Day 0 28 HA 60 μ g 20 200 Day 0 28 H
Slide 20: Peak Influenza HAI Antibody Dose Response - A/Kansas H3N2
PEAK INFLUENZA HAI ANTIBODY DOSE RESPONSE WITH INTERMEDIATE LEVELS OF HA DOSE Hemagglutination inhibition (HAI) antibody geometric mean titers (GMT) by dose and visit – A/Kansas H3N2 20 © 2022 NOVAVAX. All rights reserved. 20 200 Day 0 28 HA 60 μ g (Ref) 20 200 Day 0 28 HA 60 μ g 20 200 Day 0 28 HA
Slide 21: Peak Influenza HAI Antibody Dose Response - B/Maryland (Vic)
PEAK INFLUENZA HAI ANTIBODY DOSE RESPONSE WITH INCREASING LEVELS OF HA DOSE Hemagglutination inhibition (HAI) antibody geometric mean titers (GMT) by dose and visit – B/Maryland (Vic) 21 © 2022 NOVAVAX. All rights reserved. 20 200 Day 0 28 HA 60 μ g (Ref) 20 200 Day 0 28 HA 60 μ g 20 200 Day 0 28 HA
Slide 22: Peak Influenza HAI Antibody Dose Response - B/Phuket (Yam)
PEAK INFLUENZA HAI ANTIBODY DOSE RESPONSE WITH INTERMEDIATE LEVELS OF HA DOSE Hemagglutination inhibition (HAI) antibody geometric mean titers (GMT) by dose and visit – B/Phuket (Yam) 22 © 2022 NOVAVAX. All rights reserved. 20 200 Day 0 28 HA 60 μ g (Ref) 20 200 Day 0 28 HA 60 μ g 20 200 Day 0 28 HA
Slide 23: Modeling Can Predict an Optimal Dose of rS and HA
MODELING CAN PREDICT AN OPTIMAL DOSE OF rS AND HA Design of experiments (DoE) response surface modeling methods 23 © 2022 NOVAVAX. All rights reserved. 3 separate multiple regression modeling approaches were employed. Each approach: • Constructed 5 separate second order models ( ie , main rS and HA
Slide 24: Response Surface Modeling for Dose Optimization
MODELING CAN PREDICT AN OPTIMAL DOSE OF rS AND HA Design of experiments (DoE) response surface modeling for dose optimization 24 © 2022 NOVAVAX. All rights reserved. • We used these models to predict the impact of every permutation of combinations of HA dose and rS dose on the IgG and HAI response,
Slide 25: Using Modeling to Predict an Optimal Dose of rS and HA
USING MODELING TO PREDICT AN OPTIMAL DOSE OF rS AND HA Design of experiments (DoE) response surface modeling for dose optimization 25 © 2022 NOVAVAX. All rights reserved. The 3 different modeling approaches broadly converged on a similar set of results with regards to optimal dose combinations, incr
Slide 26: Preliminary Findings and Next Steps
PRELIMINARY FINDINGS AND NEXT STEPS 26 © 2022 NOVAVAX. All rights reserved. • The first study to demonstrate that a COVID - Influenza combination vaccine is feasible, well - tolerated, and immunogenic , and these data warrant continued development • A novel DoE modeling - based approach to dose find
Slide 27: Preliminary Findings and Next Steps
PRELIMINARY FINDINGS AND NEXT STEPS 27 © 2022 NOVAVAX. All rights reserved. • This study evaluated CIC formulations with 50μg of Matrix - M adjuvant, which was lower than the 75μg Matrix - M previously used in the standalone qNIV • A higher Matrix - M adjuvant dose of 75μg in CIC might further enhan
Slide 28: Thank You
28 © 2022 NOVAVAX. All rights reserved. THANK YOU CONTRIBUTORS VIVEK SHINDE, WAYNE WOO, SHARON LIU, SUSAN NEAL, JOYCE PLESTED, TIM VINCENT, MINGZHU ZHU, SHANE CLONEY - CLARK, IKSUNG CHO, LOU FRIES, FILIP DUBOVSKY, GREG GLENN
Slide 29: Backups
29 © 2022 NOVAVAX. All rights reserved. BACKUPS
Slide 30: The NanoFlu Vaccine: Hemagglutinin Nanoparticle Antigen and Matrix-M Adjuvant
The NanoFlu vaccine Hemagglutinin nanoparticle antigen and Matrix - M adjuvant 30 © 2022 NOVAVAX. All rights reserved. Recombinant hemagglutinin (HA) nanoparticles • Produced in a Baculovirus/Sf9 insect cell system • Expressed as recombinant , full - length, wild - type , uncleaved HA0 that assemble
Slide 31: Phase 1: NanoFlu Induced Higher Wild-Type HAI Antibody Responses
PHASE 1: NanoFlu ( tNIV ) INDUCED HIGHER WILD - TYPE HAI ANTIBODY RESPONSES (GMFRs) VS. FLUZONE - HIGH DOSE (IIV3 - HD) AGAINST 5 GENERATIONS OF ANTIGENICALLY DRIFTED A(H3N2) STRAINS Shinde et al. NEJM 2018. DOI: 10.1056/NEJMc1803554 Phase 1 design: 330 US adults aged ≥60 years Randomized 1:1:1 • tN
Slide 32: Phase 2: Summary
• Demonstration of an “ adjuvant effect ” • Matrix - M adjuvant resulted in significant enhancement of immune responses when compared to unadjuvanted formulation • Higher wild - type HAI antibody responses against homologous A/H3N2 and drifted A/H3N2 strains as compared to Fluzone HD • Similar wild
Slide 33: COVID-Influenza Combination Investigational Vaccine Design
COVID-Influenza Combination (CIC) Investigational Vaccine Design 1) Genes inserted into insect virus Final vaccine SARS-CoV-2 spike and four Influenza Hemagglutinin , vase (HA1, HA3, HAB1, HAB2) genes are engineered into Se year " baculovirus for independent expression. q , Matric M™ adiuvet ce ere
Slide 34: The NanoFlu Vaccine: Hemagglutinin Nanoparticle Antigen and Matrix-M Adjuvant
The NanoFlu vaccine Hemagglutinin nanoparticle antigen and Matrix - M adjuvant 34 © 2022 NOVAVAX. All rights reserved. Recombinant hemagglutinin (HA) nanoparticles • Produced in a Baculovirus/Sf9 insect cell system • Expressed as recombinant , full - length, wild - type , uncleaved HA0 that assemble
Slide 35: Phase 3 Immunogenicity: Enhanced Responses Against Homologous and Drifted Strains
Day 28 wild - type HAI vs wildtype Neutralizing antibody ( NanoFlu / Fluzone ) PHASE 3 IMMUNOGENICITY: ENHANCED RESPONSES AGAINST HOMOLOGOUS AND DRIFTED A/H3N2 AND B - VICTORIA STRAINS Shinde et al. Lancet ID. 2021. DOI: 10.1016/S1473 - 3099(21)00192 - 4 HAI: Wild - type Microneutralization: Wild -
Slide 36: COVID-Influenza Combination Vaccine Development
COVID - INFLUENZA COMBINATION VACCINE DEVELOPMENT JUNE 2021 Announced data from co - administration sub - study** MAY 2021 Announced positive preclinical data* SEPTEMBER 2021 Initiated phase I/II clinical trial of COVID - NanoFlu Combination Vaccine Preclinical Development Clinical Proof of Concept
Slide 37: Phase 3 Immunogenicity: Primary Endpoint Met on All Homologous Strains
PHASE 3 IMMUNOGENICITY: PRIMARY ENDPOINT MET ON ALL HOMOLOGOUS STRAINS Day 28 egg - based or wild - type HAI GMTs and GMT ratios ( NanoFlu / Fluzone ) © 2022 NOVAVAX. All rights reserved. 37 NanoFlu Fluzone Quad D28 GMT Ratio Assay Strain D28 GMT D28 GMT ( NanoFlu / Fluzone ) 95% CI HAI: EGG A/Brisb
Slide 38: Phase 3 CMI: Comparison to Enhanced Influenza Vaccines in Univ of HK Study
PHASE 3 CMI: COMPARISON TO ENHANCED INFLUENZA VACCINES IN UNIV OF HK STUDY Day 7 / 0 geometric mean fold rise (GMFRs) of IFN - γ cytokine+ total CD4+ T cells against A/H3N2 or B - Victoria strain GMFR at Day 7 NanoFlu induced substantially higher fold - rises of IFN - γ + CD4+ T cells as compared to
Slide 39: Phase 1: Egg-Adapted Reagents May Give a Misleading Result
PHASE 1: EGG - ADAPTED REAGENTS MAY GIVE A MISLEADING RESULT Microneutralization antibody responses (GMFRs) against egg - adapted vs. wild - type A/Singapore A/H3N2 virus 39 © 2022 NOVAVAX. All rights reserved. Ratio of Day 21 GMTs 61% ↑ p=0.0002 3.8 3.9 3.5 2.1 0.0 1.0 2.0 3.0 4.0 5.0 180µg NanoFlu
Slide 40: Phase 3 Safety Data Through Day 365
NanoFlu well tolerated © 2022 NOVAVAX. All rights reserved. 40 *No SAEs in either treatment group were assessed by study investigators as related to vaccine at either timepoint. Through Day 365 NanoFlu Fluzone Quad (SD) N 1333 1319 Counts (%) of Subjects with Events Any treatment emergent adverse ev