Phase 2 Dose and Formulation Confirmation of Quad-NIV in Older Adults

This randomized, observer-blind, active-controlled, Phase 2 trial will be conducted at
multiple sites. The composition of the Quad-NIV Influenza Vaccines to be used in this trial
includes recombinant H1, H3, and two B hemagglutinin proteins for the 2018-2019 Northern
Hemisphere influenza virus strains.

Approximately 1375 healthy male and female subjects ≥ 65 years will be randomized into 7
treatment groups, receiving various formulations of Quad-NIV, with or without Matrix-M1
adjuvant or one of two active comparator influenza vaccines. Within each site, randomization
will be stratified by history of receipt of 2017-2018 influenza vaccine. Subjects will
receive two injections 28 days apart. On Day 0, subjects will receive one of the five
Quad-NIV formulations or one of the two comparator influenza vaccines. On Day 28, subjects
will receive either placebo or a licensed influenza vaccine rescue dose, depending on his or
her initial randomization.

Subjects will be followed for safety for approximately one year, with primary immunogenicity
results at Day 28.

Inclusion Criteria:

1. Clinically-stable adult male or female, ≥ 65 years of age. Subjects may have 1 or more
chronic medical diagnoses, but should be clinically stable as assessed by:

- Absence of changes in medical therapy within 1 month due to treatment failure or
toxicity,

- Absence of medical events qualifying as serious adverse events within 2 months;
and

- Absence of known, current, and life-limiting diagnoses which render survival to
completion of the protocol unlikely in the opinion of the investigator.

2. Willing and able to give informed consent prior to trial enrollment, and

3. Living in the community and able to attend trial visits, comply with trial
requirements, and provide timely, reliable, and complete reports of adverse events.

Exclusion Criteria:

1. Participation in research involving investigational product (drug / biologic / device)
within 45 days before planned date of first injection.

2. Participation in any previous Novavax's influenza vaccine clinical trial(s).

3. History of a serious reaction to prior influenza vaccination, known allergy to
constituents of licensed comparator vaccines or polysorbate 80.

4. History of Guillain-Barré Syndrome (GBS) within 6 weeks following a previous influenza
vaccine.

5. Received any vaccine in the 4 weeks preceding the trial vaccination and any influenza
vaccine within 6 months preceding the trial vaccination.

6. Any known or suspected immunosuppressive illness, congenital or acquired, based on
medical history and/or physical examination.

7. Chronic administration (defined as more than 14 continuous days) of immunosuppressants
or other immune-modifying drugs within 6 months prior to the administration of the
trial vaccine. An immunosuppressant dose of glucocorticoid will be defined as a
systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical,
inhaled, and nasal glucocorticoids will be permitted.

8. Administration of immunoglobulins and/or any blood products within the 3 months
preceding the administration of the trial vaccine or during the trial.

9. Acute disease at the time of enrollment (defined as the presence of a moderate or
severe illness with or without fever, or an oral temperature ≥ 38.0°C, on the planned
day of vaccine administration).

10. Any condition that in the opinion of the investigator would pose a health risk to the
subject if enrolled or could interfere with evaluation of the vaccine or
interpretation of trial results (including neurologic or psychiatric conditions deemed
likely to impair the quality of safety reporting).

11. Known disturbance of coagulation.

12. Suspicion or recent history (within 1 year of planned vaccination) of alcohol or other
substance abuse.