recombinant nanoparticle covid-19 vaccine platform

World Vaccine Congress Europe | October 20, 2020

Recombinant Nanoparticle COVID-19 Vaccine

Platform Technology for EID

2n o v a v a x . c o m

This article was published on September 2, 2020, at NEJM.org

DOI: 10.1056/NEJMoa2026920


NVX-CoV2373 Phase 3


Novavax COVID-19 vaccine

• NVX-CoV2373 vaccine: Prefusion spike protein in a nanoparticle with Matrix-M adjuvant

• NHP challenge data

• Safety and immunogenicity update

• Clinical trial update

• NVX-CoV2373 is in clinical efficacy evaluations

• Progress towards manufacturing


Novavax vaccine pipeline

PHASE 1 PHASE 2 PHASE 3

CLINICALPRECLINICALPROGRAM DESCRIPTION

ResVax™ - RSV F Vaccine - Infants via Maternal Immunization

RSV F Vaccine - Older Adults (60+ yrs)

RSV F Vaccine - Pediatrics (6 mos – 5 yrs)

Combination Influenza/RSV F Vaccine - Older Adults (60+)

Ebola GP Vaccine

Matrix-M

Matrix-M

Matrix-M

NVX-CoV2373 – Coronavirus Vaccine CandidateMatrix-M

NanoFlu™ – Nanoparticle Seasonal Influenza Vaccine - Older Adults (65+ yrs) Matrix-M

Completed Phase 3– March 2020 Successfully achieved all primary endpoints and achieved

statistical significance in key secondary endpoints

Phase 3– Initiated in the UK September 2020; U.S. Phase 2 ongoing; Initiating U.S. Phase 3 in Q4 2020


NVX-CoV2373 vaccine design

Antigen expressed in baculovirus-S. frugiperda system• Codon-optimized• Full-length protein, including transmembrane domain

Drug substance• Native conformation trimers• Stable PS80 nanoparticle

Drug product• Co-formulated with adjuvant • Dispensed in vial• Stored 2-8O C

WT: NSPRRARSVAS

3Q: NSPQQAQSVAS

RBDNTD SD1/SD2

S1/S2 cleavage site

682-QQAQ-685

mutation

S2' cleavage

site

HR1 12731 TMHR2CH

2P mutation

K986P/V987P

WT: SRLDKVEAEV

2P: SRLDPPEAEV

NVX-CoV2373

S1 S2A

SS

FP

CT

Matrix-M adjuvant• Purified from Quillaja saponaria molina

Matrix-M adjuvant


NVX-CoV2373 in cynomolgus macaquesInduces neutralizing immune antibody in excess to convalescent human sera

Protects upper and lower airway from experimental wild-type challenge

P la c e b o

-

2 .5 g

2 5 g

5 g

5 0 g

2 5 g

5 0 g

1 0 1

1 0 2

1 0 3

1 0 4

1 0 5

1 0 6

1 0 7

B A L s g R N A c o p ie s /m L

BA

L V

ira

l lo

ad

(s

gR

NA

c

op

ies

/mL

)

L O D

C o V -2 3 7 3

M a t r i x - M

P la c e b o

-

2 .5 g

2 5 g

5 g

5 0 g

2 5 g

5 0 g

1 0 1

1 0 2

1 0 3

1 0 4

1 0 5

1 0 6

1 0 7

N a s a l S w a b s g R N A c o p ie s /m L

Vir

al

loa

d (

sg

RN

A c

op

ies

/mL

)

(M

ea

n

SE

M)

L O D

C o V -2 3 7 3

M a t r i x - M

d 2 p i

d 4 p i

2 .5 g

2 5 g

5 g

5 0 g

2 5 g

5 0 g

C o n v

n = 3 3

1 0 1

1 0 2

1 0 3

1 0 4

1 0 5

10

0%

SA

RS

-Co

V-2

Ne

utr

ali

zin

g

(CP

E A

ss

ay

)

L O D

N V X C o V 2 3 7 3

M atrix-M

Doses administered on Day 0, 21 and challenged with 10log4 IT/IN on Day 37

100% wild-type neutralization Lower airway protection Upper airway protection

bioRxiv. https://doi.org/10.1101/2020.08.18.256578

https://doi.org/10.1101/2020.08.18.256578


Rhesus macaques: upper and lower airway protectionVaccinated Day 0 and Day 21; Challenged with SARS-CoV-2 wild-type 1.05 x 106 PFU IN/IT on Day 38

No viral replication detected in upper or lower airway following experimental wild-type challenge

2 4 2 4 2 4

1

2

3

4

5

6

sg

RN

A G

en

e E

c

op

ie

s/m

L

w

as

h f

lu

id

(

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g1

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P l a c e b o

D a y s P o s t C h a l l e n g e

2 5 g v a c c i n e + 5 0 g

M a t r i x - M 1

5 g v a c c i n e + 5 0 g

M a t r i x - M 1

B A L : S u b g e n o m i c R N A

N V X - C o V 2 3 7 3

2 4 7 2 4 7 2 4 7

1

2

3

4

5

6

sg

RN

A G

en

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c

op

ie

s/m

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T

ra

ns

fe

r f

lu

id

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P l a c e b o

D a y s P o s t C h a l l e n g e

2 5 g v a c c i n e + 5 0 g

M a t r i x - M 1

5 g v a c c i n e + 5 0 g

M a t r i x - M 1

N a s a l S w a b : S u b g e n o m i c R N A

N V X - C o V 2 3 7 3

Study conducted at Texas Biomedical Research Institute


Study 1 Part 1 Partner: CEPISponsor: Novavax

• First-in-human safety and immunogenicity

• N=131; Adults 18-59 y/o in Australia

N=131 Day 0 Day 21

Antigen Matrix-M Antigen Matrix-M

A 25 Placebo Placebo

B 25 25 µg 25 µg

C 25 (+3) 5 µg + 50 µg 5 µg + 50 µg

D 25 (+3) 25 µg + 50 µg 25 µg + 50 µg

E 25 25 µg + 50 µg Placebo

Development Goal:

• FTiH safety

• Dose-selection and demonstration of adjuvant utility


High level safety summary

• No serious adverse events

• Adverse events of Special Interest

• No PIMMC AESI

• No confirmed COVID-19 AESIs

• Treatment emergent adverse events

• All mild and moderate and balanced in active arms

• Solicited reactogenicity symptoms

• Overall, reactogenicity was mild, and vaccinations were well-tolerated

• Vast majority were Grade 0 or mild

• Solicited symptoms increased with second dose in adjuvanted group

• Mean duration <2 days

• Resulted in no vaccination refusals or withdrawals


Unsolicited treatment emergent adverse eventsNo severe events reported

PlaceboPlacebo(n=23)

25ug (no adjuvant)

25ug (no adjuvant)

(n=25)

25ug+Matrix-M1 placebo(n=26)

5ug+Matrix-M1 5ug+Matrix-M1(n=29)

25ug+Matrix-M1 25ug+Matrix-M1(n=28)

Dose1 Dose 2 Dose 1 Dose 2 Dose 1 Dose 2 Dose 1 Dose 2 Dose 1 Dose 2

Mild 14%

417%

832%

520%

727%

415%

621%

4+117%

7+129%

4+118%

Moderate 21

9%0 0 12

4%16

4%17

4%13

3%14

4%15

4%0

Severe 0 0 0 0 0 0 0 0 0 0

1: Musculoskeletal Injury, Somnambulism (related)

2: Headache (related)

3: Headache

4: Hemoglobin decrease (related)

5: Biliary colic

6: Bronchitis

7: Scleritis/eye injury

Partner: CEPISponsor: Novavax


Local reactogenicity symptoms collected 7 days after each doseMajority of symptoms grade 0 or grade 1

• Local symptoms

increased after

dose 2

• Increased rate

and severity in

Matrix-M1 groups

• Pain and

tenderness were

reported most

common

• Mean duration < 2

days

0%

25%

50%

75%

100%

Grade 0 (None) Grade 1 (Mild) Grade 2 (Moderate) Grade 3 (Severe)

0%

25%

50%

75%

100%

25µ

g +

Matr

ix-M

1

5µ

g +

Matr

ix-M

1

Pla

cebo

25µ

g +

Matr

ix-M

1

5µ

g +

Matr

ix-M

1

Pla

cebo

25µ

g +

Matr

ix-M

1

5µ

g +

Matr

ix-M

1

Pla

cebo

25µ

g +

Matr

ix-M

1

5µ

g +

Matr

ix-M

1

Pla

cebo.

25µ

g +

Matr

ix-M

1

5µ

g +

Matr

ix-M

1

Pla

cebo

PainTendernessErythemaSwelling.Any Solicited Local AEs

Va

cc

ina

tio

n 1

Va

cc

ina

tio

n 2

Partner: CEPI

Sponsor: Novavax


Systemic reactogenicity symptoms collected 7 days after each doseMajority of symptoms grade 0 or grade 1

• Systemic

symptoms

increased after

dose 2

• Increased rate

and severity in

Matrix-M1

groups

• Headache,

fatigue and

myalgia were

most

commonly

reported

• Mean duration

< 2 days

0%

25%

50%

75%

100%Grade 0 (None) Grade 1 (Mild) Grade 2 (Moderate) Grade 3 (Severe)

0%

25%

50%

75%

100%

25µ

g +

Matr

ix-M

1

5µ

g +

Ma

trix

-M1

Pla

cebo

25µ

g +

Matr

ix-M

1

5µ

g +

Matr

ix-M

1

Pla

cebo

25µ

g +

Matr

ix-M

1

5µ

g +

Ma

trix

-M1

Pla

cebo

25µ

g +

Matr

ix-M

1

5µ

g +

Ma

trix

-M1

Pla

cebo

25µ

g +

Matr

ix-M

1

5µ

g +

Ma

trix

-M1

Pla

cebo

25µ

g +

Matr

ix-M

1

5µ

g +

Ma

trix

-M1

Pla

cebo

25µ

g +

Matr

ix-M

1

5µ

g +

Ma

trix

-M1

Pla

cebo.

25µ

g +

Matr

ix-M

1

5µ

g +

Ma

trix

-M1

Pla

cebo

MalaiseNauseaMyalgiaHeadacheFeverFatigueArthralgia.Any SolicitedSystemic AEs

Va

cc

ina

tio

n 1

Va

cc

ina

tio

n 2

Partner: CEPI

Sponsor: Novavax


Anti-S IgG ELISA through Day 35


Reverse cumulative distribution of anti-S IgG ELISA Day 35Matrix-M1 is dose-sparing: 5ug + Matrix-M1 and 25ug +Matrix-M1 is comparably immunogenic

100% IgG seroconversion response in 2 dose schedule with Matrix-M1

Placebo2 Dose 25ug no adjuvant

1 Dose 25ug + Matrix-M1



Keech et al. NEJM 02 September 2020


Anti-Spike IgG ELISA KineticsVaccination on Day 0 and D21; Peak immune response on Day 35 in 2 dose schedule

Matrix-M1 required for optimal immune response; 2 doses schedule superior to 1 dose schedule

Placebo

2 Doses: 25ug (no adjuvant)

1 Dose: 25ug + Matrix-M1

2 Doses: 25ug + Matrix-M1

2 Doses: 5ug + Matrix-M1

Partner: CEPI

Sponsor: Novavax

Pre-publication data


Wild-type virus neutralization through Day 35


Reverse cumulative distribution of 100% wild-type virus neutralization*5ug + Matrix-M1 and 25ug + Matrix-M1 induce high levels of functional antibody100% neutralization seroconversion response in 2 dose schedule with Matrix-M1

2 Dose 25ug

no adjuvant

1 Dose 25ug

+ Matrix-M1

2 Dose

25ug

+ Matrix-M1

2 Dose 5ug

+ Matrix-

M1

* Dr Matthew Frieman Lab UMSOM

Partner: CEPI

Sponsor: Novavax

CONFIDENTIAL


Placebo

25ug x 2 doses (no Matrix-M)

25ug + 50ug Matrix-M x 1 dose



100% wild-type neutralizing titer kinetics

CONFIDENTIAL


Scatter plot of IgG vs wild-type neutralizationAdjuvanted vaccine induces IgG response that correlates tightly with neutralization response

Significant and consistent proportion of antibody is functional


50ug25ug13ug6.5ug

1 dose, MM

2 dose, MM

2 dose

Anti-GP IgG

Persistence of immunity with a nanoparticle vaccine in humans: Anti-

Ebola GP IgG


Anti-GP IgG

Persistence of immunity with a nanoparticle vaccine in baboons: Anti-Ebola GP

Fries, et al. Ebolavirus glycoprotein subunit vaccine with

saponin Matrix-M™ adjuvant is highly protective against

virulent human ebolavirus Zaire in Macaca fascicularis:

An alternative to virus vector-based vaccines; in

preparation.

Boost


Intracellular cytokine staining Ag-specific CD4 T cells analysisMatrix-M induced Th1-biased immune response as predicted by non-clinical data

2 Doses: 5ug + Matrix-M 2 Doses: 25ug+ Matrix-MPlacebo



Intracellular cytokine staining Ag-specific CD4 T cells analysis (CD45+, CCR7-)

Double and triple Th1 cytokine response compared to double Th2 cytokine response

2 Doses: 5ug + Matrix-M 2 Doses: 25ug + Matrix-M



NVX-CoV2373 clinical development plan

Dose confirmation based on Phase 1 data Aug 2020

Triggers: Phase 2 US/Australia (dose confirmation in >60 y)Phase 2b South Africa efficacy study 18-65 yPhase 2/3 UK efficacy study 18-84 y

1 2

1

SafetyImmunogenicity

Includes Efficacy Assessment2

Partner/Funder

Dose confirmation in adults >60 y based on Phase 2: Oct 2020

CEPI

CEPI

Phase 3 US N=30,000 Adults ≥18 yearsSTUDY 72019nCoV-301

Phase 3 UK N= up to 10,000 18-84 yearsSTUDY 32019nCoV-401

BMGF

UKVTF

OWS

Phase 2b South Africa N=up to 4,404 18-65 years (n=240 HIV+)STUDY 22019nCoV-501

Phase 2 AU/US Adults N=1,500 (n=750 >60 years)STUDY 1Part 2 (2019nCoV-101)

Phase 1 AU Adults N=131 , 18-59 yearsSTUDY 1Part 1 (2019nCoV-101)


Novavax COVID-19 vaccine

• NVX-CoV2373 vaccine: Prefusion spike protein in a nanoparticle with Matrix-M adjuvant• The vaccine is stable and will utilize the standard cold chain

• Appears safe in vaccines, with majority reporting no or mild reactions after immunization

• Induces robust spike IgG, wild-type neutralizing antibodies at levels that exceed convalescent sera

• Induces polyfunctional T cells

• NVX-CoV2373 is in clinical efficacy evaluations

• The vaccine is based on mature technologies


Looking ahead

• The nanoparticle spike protein vaccine is highly immunogenic, which bodes well for efficacy

• Observed dose sparing (5ug) greatly expands the vaccine supply

• Global supply chain may produce up to 2 billion annualized doses when at full capacity in 2021

• NVX-CoV2373 has entered pivotal trial/efficacy evaluations

• The UK trial is expected to support licensure

• The US OWS-supported trial is expected to start soon

Questions?

recombinant nanoparticle covid-19 vaccine platform

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