Efficacy Data Updates from Novavax' Protein-based Vaccine Candidate - New York Academy of Sciences
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Efficacy Data Updates from Novavax’
Protein-based Vaccine Candidate
New York Academy of Sciences
Nasdaq: NVAX | February 2, 2021
Certain information, particularly information relating to future performance and other business matters,
including expectations regarding clinical development, market opportunities and anticipated milestones
constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act.
Forward-looking statements may generally contain words such as “believe,” “may,” “could,” “will,”
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“expect,” “should,” “would,” or “assume” or variations of such words or other words with similar meanings.
Novavax cautions that these forward-looking statements are subject to numerous assumptions, risks and
uncertainties that change over time and may cause actual results to differ materially from the results
discussed in the forward-looking statements.
Uncertainties include but are not limited to clinical trial results, dependence on third party contractors,
competition for clinical resources and patient enrollment and risks that we may lack the financial resources
Safe Harbor to fund ongoing operations.
Statement Additional information on Risk Factors are contained in Novavax’ filings with the U.S. Securities and Exchange
Commission, including our Annual Report on Form 10-K for the year ended December 31, 2019, our Quarterly
Reports on Form 10-Q, and our Current Reports on Form 8-K, which are all available at http://www.sec.gov.
Forward-looking statements are based on current expectations and assumptions and currently available
data and are neither predictions nor guarantees of future events or performance.
Current results may not be predictive of future results.
You should not place undue reliance on forward-looking statements which speak only as of the date hereof.
The Company does not undertake to update or revise any forward-looking statements after they are made,
whether as a result of new information, future events, or otherwise, except as required by applicable law.
Matrix-M and NanoFlu are trademarks of Novavax, Inc.
novavax.com 2
Agenda
• Review of NVX-CoV2373 program
• Clinical development updates
§ Preclinical
§ Phase 1-2 studies
§ Phase 2b & 3 efficacy studies
• Next steps: Bivalent approach
• Manufacturing
novavax.com 3
NVX-CoV2373
Progress Built
Upon Years of
Vaccine Research
novavax.com 4
NVX-CoV2373 Vaccine Design
Vaccine Platform Technology: Nanoparticle vaccine formulated with Matrix-M™
Antigen Drug Substance Drug Product
• Expressed in baculovirus (S. frugiperda) system • Native conformation trimers • Co-formulated with adjuvant
• Full-length protein, including transmembrane domain • Stable PS80 nanoparticle • Dispensed in 10-dose vial
• Furin cleavage site mutated and stabilized • Stored 2-8oC, ready-to-use
NVX-CoV2373
A S1 S2
S1/S2 cleavage site 2P mutation
682-QQAQ-685 K986P/V987P
SS mutation FP CT
1 NTD RBD SD1/SD2 HR1 CH HR2 TM 1273
S2' cleavage
site
WT: NSPRRARSVAS WT: SRLDKVEAEV
3Q: NSPQQAQSVAS 2P: SRLDPPEAEV
Matrix-M adjuvant
• Purified from Quillaja saponaria molina
Bangaru et al. bioRxiv 06 August 2020 and Tian et al. bioRxiv 30 June 2020
novavax.com 5
Saponin Adjuvant/Nanoparticle, Influenza Antigen Drift
More RBD & HA1/HA2 Epitopes Recognized
More – and thicker – bars represent increased
distribution and frequencies of antibodies to Unadjuvanted
unique epitopes on the antigen.
Saponin adjuvant results in epitope spreading In
three serial trials, vaccine induced H3N2 HAI Adjuvanted
showed good responses to drifted strains.
SARS-CoV-2 will clearly undergo antigenic drift
Adjuvanted
Chung, K.Y., et al., 2015. DOI: 10.1016/j.vaccine.2015.06.047
Portnoff, A.D., et al., 2020. DOI: 10.3390/vaccines8010099
Shinde, V., et al., 2020. DOI: 10.1093/cid/ciaa1673
novavax.com 6
NVX-CoV2373 Protected Lower & Upper Airways in Rhesus Macaques
No viral replication observed following Day 38 challenge with WT SARS-CoV-2
B A L : SLower
u b g e n oAirway
m ic R N A N a s a l SUpper
w a b : SAirway
u b g e n o m ic R N A
Placebo
P la c e b o
NVX-CoV2373
N V X -C o V 2 3 7 3 PPlacebo
la c e b o NNVX-CoV2373
V X -C o V 2 3 7 3
6 6
5 µ g v a c c in e + 5 0 µ g
c o p ie s /m L
c o p ie s /m L
5 5
5 µg vaccine 5 µ g
)
M a tr ix -M 1
10
v a c c in e + 5 0
)
+ 50 mg Matrix-M
10
T r a n s f e r flu id ( lo g
2 5 µ g v a c c in e + 5 0 µ g
M a tr ix -M 1
( lo g
M a tr ix -M 1
4 4 25 µg vaccine 2 5 µ g v a c c i n e + 5
+ 50 mg Matrix-M M a t r i x - M 1
f lu id
G e n e E
E
G e n e
3 3
w a s h
s g R N A
s g R N A
2 2
1 1
2 4 2 4 2 4 2 4 7 2 4 7 2 4 7
D a Days
y s P oPost
s t C Challenge
h a lle n g e D aDays
y s P Post
o s t Challenge
C h a lle n g e
novavax.com 7
NVX-CoV2373 Clinical Development Plan
Study 1
Part 1 (2019nCoV-101) Phase 1 AU N=131; 18-59 years
Study 1 Safety and
1 Part 2 (2019nCoV-101) Phase 2 AU/US N=1,288; 18-84 years (n=583 >60 years) Immunogenicity
Includes Efficacy
Assessment
Study 2
(2019nCoV-501) Phase 2b South Africa N=4,422; 18-84 years (n=240 HIV+)
Ongoing study
Study 3
2019nCoV-302 Phase 3 UK N=15,203; 18-84 years (n=400 IIV co-admin)
Study 4
Sponsor = SIIPL Phase 3 India N=1,600; 18-65 years (Novavax vs SIIPL)
Study 5
(2019nCoV-502) Phase 2 Czech N=120; 12-59 years
Study 6
2 Sponsor = Takeda Phase 2 Japan N=450; 20-65 years
Study 7
2019nCoV-301 Phase 3 US/Mexico N=30,000; ≥18 years
1 Dose confirmation based on Phase 1 data: Aug 2020
2 Dose confirmation in adults >60 y based on Phase 2: Oct 2020
novavax.com 8
NVX-CoV2373
Phase 1-2 Study
(US & Australia)
novavax.com 9
US and Australia Phase 1 Study Design
N= 258 5 µg + 50 µg Matrix-M™
(2 injections: Day 0 and Day 21)
25 µg + 50 µg Matrix-M
(2 injections: Day 0 and Day 21)
131
R 25 µg
Adults R
1:1:1:1:1 (2 injections: Day 0 and Day 21)
18-59 years
N= 255 25 µg + 50 µg Matrix-M Placebo
(Day 0) (Day 21)
N= 255 Placebo
(2 injections: Day 0 and Day 21)
Reactogenicity data reviewed by SMC & FDA in advance of Phase 3 study
novavax.com 10Phase 1:
Spike IgG and Neutralization Response at Day 35
GMEU 63,160 47,521 8,344 GMT 3,906 3,305 983
95% CI (47,117; 84,666) (33,803; 66,804) (4,420; 15,747) 95% CI (2,556; 5,970) (2,205; 4,953) (579; 1,670)
Keech, C. et al. DOI: 10.1056/NEJMoa2026920
novavax.com 11Phase 1: Spike IgG Response Through Six Months
Matrix-MTM required for optimal immune response; 2 adjuvanted doses superior to 1 dose
Matrix-M is dose-sparing
Convalescent Sera
(Median & CI; 20d post illness)
2 Doses: 25 µg + Matrix-M
2 Doses: 5 µg + Matrix-M
1 Dose: 25 µg + Matrix-M
2 Doses: 25 µg (no adjuvant)
Placebo
Phase 1: n = 131; 18-59 years of age; Vaccination on Day 0 and D21 (pre-publication)
novavax.com 12Adjuvanted Vaccine Induces IgG Response
that Correlates Tightly with Neutralization Response
Significant and consistent proportion of antibody is functional
2 Dose 5µg + Matrix-M™
combined with
Convalescent Serum (Baylor) 2 Dose: 25µg (no adjuvant) 2 Dose 25µg + Matrix-M™
Keech, C. et al. DOI: 10.1056/NEJMoa2026920
novavax.com 13US and Australia Phase 2 Study Design
Includes ~50% of adults age 60-84 years
N= 258 5 µg + 50 µg Matrix-M™
(2 injections: Day 0 and Day 21)
N= 259 25 µg + 50 µg Matrix-M
(2 injections: Day 0 and Day 21)
1,288
R 5 µg + 50 µg Matrix-M Placebo
Adults 1:1:1:1:1 (Day 0) (Day 21)
>18 years
N= 255 25 µg + 50 µg Matrix-M Placebo
(Day 0) (Day 21)
N= 255 Placebo
(2 injections: Day 0 and Day 21)
novavax.com 14Phase 2: Reproduced Phase 1 Lessons
2 Matrix-M™-adjuvanted doses of 5 µg and 25 µg induced comparable, robust immune responses
Consistent with Phase 1 data
2 Doses: 25 µg + Matrix-M
2 Doses: 5 µg + Matrix-M
5 µg
1 Dose: 25 µg + Matrix-M
1 Dose: 5 µg + Matrix-M
Placebo
Phase 2: n =1288; ≥ 18 years of age (n = 583 >60 years of age) (pre-publication)
novavax.com 15Phase 2 Local Reactogenicity: Well-tolerated
Many participants experienced no reactions, and when they did occur,
all were mild-to-moderate in severity with a mean duration ~2 Days
All Subjects Ages 18 to 59 Ages 60 to 84
100% Grade 3
Grade 2
75%
Grade 1
Vaccination 1 50%
Grade 0 (none)
• Pain and Tenderness
25%
reported most
Percent of frequently
0%
Participants
Reporting • Rates after Dose 2
Reactogenicity 100% were higher in
adjuvanted groups
75%
• Reactogenicity
Vaccination 2 50% attenuated in
adults >60 years of
25%
age
0%
Placebo 5 µg + Placebo 5 µg + Placebo 5 µg +
Matrix-M™ Matrix-M™ Matrix-M™
Worst grade reported for 7 days after each dose. Raw blinded data Oct 5 cut-off (pre-publication data)
novavax.com 16Phase 2 Systemic Reactogenicity: Well-tolerated
Many participants experienced no reactions, and when they did occur,
all were mild-to-moderate in severity with a mean duration ~2 Days
All Subjects Ages 18 to 59 Ages 60 to 84
100% Grade 4
Grade 3
75%
Grade 2
Vaccination 1 50% Grade 1
Grade 0 (none)
25%
Percent of • Fatigue, Headache
0% and Myalgia
Participants
Reporting reported most
100% frequently
Reactogenicity
• Increased rates seen
75%
in adjuvanted
Vaccination 2 groups especially
50% after Dose 2
25% • Reactogenicity
attenuated in
adults >60 years of
0%
age
Placebo 5 µg + Placebo 5 µg + Placebo 5 µg +
Matrix-M™ Matrix-M™ Matrix-M™
Worst grade reported for 7 days after each dose. Raw blinded data Oct 5 cut-off (pre-publication data)
novavax.com 175µg Dose is Well-tolerated,
with Strong and Consistent Responses
Phase 1-2 Summary
• Consistent results from Phase 1 and Phase 2
• Immunogenicity
§ High levels of antibody maintained through six months (Phase 1)
§ Antibody responses compare favorably to convalescent response
• Safety
§ No SAEs, no AESIs, AEs balanced and mostly mild/moderate
§ Vaccine well-tolerated with symptoms of ~2-day duration
• Confirmed 5µg dose for late-stage development
novavax.com 18NVX-CoV2373
UK
Phase 3 Study
novavax.com 19UK Phase 3 Study Design
Randomized, observer-blinded, placebo-controlled trial evaluating efficacy, immunogenicity and safety
5 µg + 50 µg Matrix-M™
(2 injections: Day 0 and Day 21)
15,000 n = ~7,500
Adults R
>18 years 1:1
25% > age 65 Placebo
(2 injections: Day 0 and Day 21)
n = ~7,500
• Primary endpoint: PCR-positive symptomatic mild, moderate or severe COVID-19 illness
diagnosed ≥ 7 days after second dose
• LBCI >30 success criteria; with success Interim analysis, became final analysis
novavax.com 20UK 501Y.V1 Mutant Strain Increased in Prevalence
During Efficacy Collection Window
20I/501Y.V1
Efficacy Endpoint Accrual:
November 11 – January 1
Figure Source: nextstrain.org
novavax.com 21Primary Endpoint Met in Interim Analysis
Severity NVX-CoV2373 Placebo
(n=7,016) (n=7,033)
Total (n=62) 6 56
Mild 1 15
Moderate 5 40
Severe 0 1
89.3%
Vaccine Efficacy
(95% CI: 75.2, 95.4)
• Preliminary PCR data show >50% of cases attributable to UK 501Y.V1 escape variant
• Final analysis to be conducted once at least 100 cases accrued
Primary Endpoint: PCR-confirmed mild, moderate, or severe COVID-19 illness occurring ≥7 days after second dose in baseline seronegative participants
novavax.com 22PCR-Confirmed Mild, Moderate or Severe COVID-19
by Strain (Ancestral vs 501Y.V1 Variant)
NVX-CoV2373 Placebo
(n=7016) (n=7033)
501Y.V1 Ancestral Unknown 501Y.V1 Ancestral Unknown
PCR-Confirmed COVID-19
4 1 1 28 23 5
(Mild, Moderate, Severe)
Mild 1 0 0 5 7 3
Moderate 3 1 1 22 16 2
Severe 0 0 0 1 0 0
Post-hoc analysis based on PCR from 56 of 62 cases:
96/94% Primary/Moderate-Severe efficacy in the ancestral COVID-19 strain;
86/87% efficacy in the 501Y.V1 variant strain.
novavax.com 23Favorable Preliminary Safety Profile
Event NVX-CoV2373 Placebo
(n=7,016) (n=7,033)
Any Severe TEAE 81 (1.1 %) 53 (0.7%)
Treatment Emergent Adverse Event
Any Serious TEAE 31 (0.4%) 30 (0.4%)
Treatment Emergent Adverse Event
Any MAAE 202 (2.7%) 201 (2.8%)
Medically Attended Adverse Event
Due to topline data, limited safety available
novavax.com 24NVX-CoV2373
South Africa
Phase 2b Study
novavax.com 25South Africa Phase 2b Study Design
Randomized, observer-blinded, placebo-controlled trial evaluating efficacy, immunogenicity and safety
5 µg + 50 µg Matrix-M™
(2 injections: Day 0 and Day 21)
4,400
n = ~2,200
Adults R
18-65 years 1:1
(n=245 HIV+) Placebo
(2 injections: Day 0 and Day 21)
n = ~2,200
Partner: BMGF
Sponsor: Novavax
• Enrollment population includes cohort of 245 randomized participants who are HIV-positive
• Efficacy analysis at 23 - 50 events, LBCI success ≥0.
• Primary endpoint: PCR-positive symptomatic mild, moderate or severe COVID-19 illness
diagnosed ≥ 7 days after second dose
novavax.com 26South Africa 501Y.V2 Escape Mutant Dominant
During Efficacy Collection Window
20H/501Y.V2
Efficacy Endpoint Accrual:
November 23 – December 30
Figure Source: nextstrain.org
novavax.com 27Previous Infection Did Not Protect
Against COVID Due To Variant
• Volunteer sera tested for SARS-CoV-2 spike IgG at Day 0
• ~30% had evidence of previous infection
§ Likely non-501Y.V2 due to enrollment timing
• No difference in rates of infection/reinfection
• Placebo ITT population (7 days post-dose 1), symptomatic COVID
§ Seronegative: 3.9% (58/1494; 2.961; 4.990): 2.3% Mod/Severe (35/1494)
§ Seropositive : 3.9% (26/674; 2.535; 5.601); 2.4% Mod /Severe (16/674)
novavax.com 28Cross-Protection Demonstrated
Against South Africa Escape Variant
NVX-CoV2373 Placebo
(n=1,357) (n=1,327)
Cases 15 29
Primary
Endpoint Vaccine Efficacy 49.4%
(95% CI: 6.1*, 72.8)
Cases 11 27
HIV– 60.1%
Vaccine Efficacy
(95% CI: 19.9, 80.1)
• Preliminary sequencing data (n=27) show 25/27 (93%) attributable to SA 501Y.V2 escape variant
• 1 severe case in placebo
• Success criteria: LBCI ≥0
Primary Endpoint: PCR-confirmed mild, moderate, or severe COVID-19 illness occurring ≥7days after second dose in baseline seronegative participants
novavax.com 29Comparison of PP Efficacy: Seropositive vs Seronegative
Serostatus NVX-CoV2373 Placebo Efficacy
% (n/N) % (n/N) (95% CI)
- 1.1% (15/1357) 2.2% (29/1327) 49.4% (6.1, 72.8)
+ 1.2% (6/500) 2.5% (13/514) 52.6% (-23.8, 81.8)
+/- 1.1% (21/1857) 2.3% (42/1841) 50.4% (16.6, 70.5)
Primary – mild/moderate/severe (HIV- & HIV+)
novavax.com 30NVX-CoV2373
PREVENT-19
US & Mexico
Phase 3 Study
novavax.com 31PREVENT-19 Phase 3 Trial Currently Enrolling
Randomized, observer-blinded, placebo-controlled trial evaluating efficacy, immunogenicity and safety
5 µg + 50 µg Matrix-M™
(2 injections: Day 0 and Day 21)
n = ~20,000
30,000
R
Adults 2:1
>18 years
Enrollment goals: Placebo
25% > age 65 years (2 injections: Day 0 and Day 21)
15% Black/African American n = ~10,000
10-20% LatinX
1-2% American Indian
• Primary endpoint: PCR-positive symptomatic mild, moderate or severe COVID-19 illness
diagnosed ≥ 7days after second dose
• Interim analysis at 72 events, final analysis at 144 events*
*Protocol version 3.0 to be updated on website
novavax.com 32PREVENT-19 Phase 3 Enrollment Update
Characteristic Current Status
Total Randomized 19,438
as of February 1, 2021
≥ 65 Years 16%
Black/African American 13%
LatinX 16%
• Enrollment expected to complete first half of February
• Unblinding rate: 1.5% overall, 55% of which are ≥ 65 years
• January 25: Protocol amended to incorporate blinded crossover
novavax.com 33PREVENT-19 Enrollment is in US Hotspots
Higher attack rates mean:
ü Increased vaccine demand
& trial participation
ü Faster endpoint accrual
A quicker path to determining
vaccine efficacy
As of January 13, 2020
novavax.com 34Variant Strains On The Rise in the US
20I/501Y.V1
First Person Dosed:
December 27
Last Person Dosed:
Late February
https://www.washingtonpost.com/nation/2021/01/30/covid-coronavirus-updates/
Figure Source: nextstrain.org
novavax.com 35Booster / Bivalent
Vaccine
Development
novavax.com 36Variant Strains Already Under Development
Against Emerging COVID-19 Mutations
• To address an evolving pandemic, the optimal vaccine for all
regions may need to contain multiple strains
• Lab-scale manufacturing underway for multiple strains
• Will be able to rapidly scale up production of additional
recombinant protein vaccine candidates as new molecular
entity (rS) is biochemically very similar to NVX-CoV2373
novavax.com 37UK and SA Variants: Production in Sf9 Cells
1 2 3 4 5 6
Lane Sample
rS 1 Mwt
UK Variant
2
BV2425.1.1, 2.1 a
UK Variant
3
BV2425.1.1, 2.1 b
4 Mwt
SA Variant
5
BV2426.1.1, 2.1 a
SA Variant
6
BV2426.1.1, 2.1 b
Western blot anti-rS polyclonal antibody
novavax.com 38NVX-CoV2373
Manufacturing &
Distribution
novavax.com 39Global Supply Chain Established
Annual capacity of over 2 billion* doses starting in 2021
PolyPeptide
Group
AGC
Biologics
Novavax AB
FujiFilm
Par Pharma UK SK
AGC Novavax CZ Bioscience
Biologics Novavax Biofabri Takeda
HQ MD
PolyPeptide Baxter Siegfried Serum
FujiFilm
Group Institute
FujiFilm NC
TX
Novavax facilities
Vaccine distribution & license agreement
Matrix-M™ production
Antigen production
Fill/Finish
* When all planned capacity is online by mid-2021
novavax.com 40Summary
novavax.com 41Two Independent Trials Demonstrate Statistically
Significant Efficacy of NVX-CoV2373
• Overall UK Phase 3 Vaccine Efficacy = 89.3%
§ Ancestral/Strain matched VE = 95.6%
§ UK Variant 501Y.V1 VE = 85.6%
• ZA Phase 2b Vaccine Efficacy = 60.1%
§ Prior infection does not protect against COVID due to 501Y.V2 variant
§ Conversely, NVX-CoV2373 achieved protection against 501Y.V2
• Data indicate Matrix-M™-adjuvanted nanoparticle highly efficacious
• Technology can rapidly adapt to make 501Y.V2 variant -rS
§ Candidate has been produced at lab-scale
novavax.com 42Acknowledgements
• UK-Paul Heath, St Georges, London
§ Seth Toback, Novavax
• Shabir Mahdi-University of Witswatersrand, Johannesburg
§ Vivek Shinde, Novavax
• Filip Dubovsky, CMO, Novavax
The Great team at Novavax, UK and South Africa
Sincere thanks to the many volunteers
novavax.com 43novavax.com 44
NVX-CoV2373 Neutralizing RBD Epitopes Bind
to Internal and External Trimer Faces
NVX-CoV2373 Monoclonal Neutralizing Epitopes NVX-CoV2373 Polyclonal IgG Epitopes
RBD RBD
RBD
RBD
Zost, et al., Nature, 2020 Greany, et al., bioRxiv, 2021 Ward, et al. Scripps, 2021
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