Wedbush PacGrow Healthcare Conference
August 2015
Safe Harbor Statement
Certain information contained herein, particularly information 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, our planned use of the proceeds from this offering, and anticipated milestones constitute forward‐looking statements within the meaning of the Private Securities Litigation Reform Act. Forward‐looking statements can be identified by the fact that they do not relate strictly to historical or current facts and generally contains words such as “believe,” “may,” “could,” “will,” “possible,” “can,” “estimate,” “continue,” “ongoing,” “consider,” “anticipate,” “intend,” “seek,” “plan,” “project,” “expect,” “should,” “would,” or “assume” or any variations of such words or other words with similar meanings, although all forward‐
looking statements do not contain these identifying words. 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 the conduct, timing and results of our clinical trials; 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, including our Annual Report on Form 10‐K, Quarterly Reports on Form 10‐Q, and Current Reports on Form 8‐K, which are 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. 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, 2
or otherwise, except as required by applicable law.
Investment Highlights
Announced data from 3 of 4 clinical trials expected in the 3rd quarter
• Ebola GP Vaccine
• Quadrivalent Seasonal Influenza
• RSV F Vaccine in older adults
• RSV F Vaccine to protect infants via maternal immunization
Novavax Vaccine Platform
• Recombinant nanoparticles that induce robust and functional immunity
• Matrix‐M adjuvant that increases the magnitude and quality of immune response to certain vaccine candidates
Strong Vaccine Development Infrastructure
• Commercial GMP manufacturing capacity
• Experienced management team 3
Product Pipeline
Program
Preclinical
Phase 1
Phase 2
Phase 3
Funding Support
RSV
Older Adults
*
Infants (Maternal Immunization)
Pediatrics (6 mos – 6 yrs)
Influenza
Quadrivalent Seasonal
Combination Respiratory
New Vaccines
Pandemic (H7N9 + Matrix‐M)
Ebola + Matrix‐M *Our funding and development arrangement with PATH expired in April 2015
4
Phase 1 Ebola GP Vaccine Clinical Trial in Healthy Adults
Trial Overview
Goal: evaluate the safety and immunogenicity
GP dose‐escalation trial, with and without Matrix‐M™ adjuvant
230 healthy adults 18 ‐ 49 years of age
Participants received either one or two intramuscular injections of 6.5µg ‐ 50µg of antigen on study days 0 and 21
Immunogenicity was assessed at multiple time points
Results
Well‐tolerated; significant antigen dose‐sparing
GP with adjuvant highly immunogenic at all dose levels
•
•
Adjuvanted two‐dose regimen induced Ebola anti‐GP antibody GMEU 45,000 ‐ 70,000, a 500 to 750‐fold rise over baseline at day 35 Adjuvanted single dose regimen induced GMEU 1700 ‐ 3400, a 21 to 27‐fold rise over baseline at day 35
GMEU: Geometric Mean ELISA Units
5
Phase 2 Quadrivalent Seasonal Influenza VLP Clinical Trial in Healthy Adults
Trial Overview
Conducted under HHS BARDA contract
400 healthy adults 18 ‐ 49 years of age
Primary outcomes assessed safety and tolerability and quantified immune responses to each of the four influenza strains based on hemagglutination‐inhibiting antibody (HAI) titers
Secondary outcomes evaluated safety neuraminidase‐inhibiting antibody titers (NAI) for all four influenza strains
Results
Met immunogenicity targets and demonstrated potential to meet the CBER criteria for accelerated approval
Robust HAI titer responses, approximately 50% greater than those in our prior phase 2 trial
Detected significant NAI antibody responses to all four influenza strains
CEBR: Center for Biologic al Evaluation and Research
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Novavax Platform Technology
Click here to view video
7
Novavax Novel RSV F Vaccine
Novavax has developed a novel RSV Fusion‐protein vaccine (RSV F Vaccine) using recombinant nanoparticle technology
Novavax has completed extensive studies in relevant preclinical models that demonstrated the vaccine is safe, immunogenic and highly efficacious in animals In addition to microneutralizing antibodies, Novavax has pioneered the use of palivizumab competing antibodies (PCA) as a measure of a functional, vaccine‐induced immune response
Prior to the initiation of this trial, Novavax has completed or initiated six clinical trials of our RSV F Vaccine demonstrating safety and immunogenicity in over 2,000 participants
The body of preclinical and clinical data, and the safety and immunogenicity in the Phase 1 trial in older adults, suggested that the efficacy of the vaccine should be tested in this population 8
Phase 2 RSV F Vaccine Clinical Trial in Older Adults
In October 2014, we initiated a Phase 2 clinical trial in older adults (clinically stable adults 60 years of age or older) The goals were to evaluate the incidence of symptomatic RSV illness in this population and describe the vaccine effect upon these illnesses
The trial was a randomized, observer‐blinded, placebo‐controlled study of 1600 older adults at 10 sites in the United States during the 2014‐15 RSV season 135 µg dose of RSV F Vaccine without adjuvant
All subjects with symptomatic respiratory illness were tested for the presence of RSV and other respiratory viruses using PCR
One of the largest prospective epidemiological RSV trials conducted in older adults
9
Study Objectives
Primary
Evaluate the incidence of all symptomatic respiratory illnesses due to RSV, medically attended illness and hospitalization, in community‐living older adults who have been treated with placebo
Examine the amplitude and duration of anti‐F IgG antibody responses
Evaluate safety and tolerability of the vaccine
Secondary
Evaluate amplitude and duration of palivizumab‐competing antibody (PCA) responses and microneutralizing antibodies to RSV A and B viruses
10
Exploratory Objectives and Ad Hoc Evaluation
Estimate the efficacy of RSV F vaccine on all symptomatic RSV respiratory illnesses and all RSV lower respiratory tract infections (LRTI)
Explore the potential correlation of the above‐listed immune responses with risk of RSV illness
Describe the spectrum of other viral and bacterial agents associated with symptomatic respiratory illness
Estimate the efficacy of the vaccine on symptomatic RSV LRTI with symptoms associated with difficulty breathing
11
Study Population and Demographics
RSV F Vaccine
Placebo
Safety
798
801
Intent‐to‐Treat
798
798
Per‐Protocol
759
771
42.0
41.7
69.4 (6.5)
69.5 (6.4)
82.7
82.1
17
17.9
White
90.4
90.9
Black
7.8
7.5
Other
1.8
1.6
Study Populations
Percent Male
Mean Age, yrs (SD)
Percent 60‐75 yrs
Percent >75 yrs
Race (%)
12
Results: Epidemiology of RSV in Older Adults
4.9% with symptomatic RSV infections
•
Pharyngitis, nasal congestion, cough, wheezing, shortness of breath or increased sputum production
95% of RSV infected subjects with LRTI symptoms
•
Cough, wheezing, shortness of breath or increased sputum production
First RSV case detected October 31, 2014
Last RSV case April 26, 2015
13
Relative Risk and Efficacy Estimates
Population
Endpoint
ITT
Per protocol
Placebo
Active
Total N
798
798
All symptomatic RSV 39
23
0.590 (0.356‐0.978) 41.3%
RSV LRTI
37
21
0.568 (0.335‐0.961) 43.2%
Total N
771
759
All symptomatic RSV 38
21
0.561 (0.333‐0.947) 43.9%
RSV LRTI
36
19
0.536 (0.310‐0.926) 46.4%
636
630
31
17
135
129
7
4
798
798
60 to <75 yrs Total N
All symptomatic RSV ≥ 75 yrs Total N
All symptomatic RSV Hosp/MARI Total N
All symptomatic RSV 0/pending
RR (95% CI)
Efficacy
0.557 (0.311‐0.998) 44.3%
0.581 (0.171‐1.975) 41.9%
0/pending
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Ad Hoc Analysis of LRTI and Difficulty Breathing
Measures of more severe illness:
Number of Symptoms
and Signs Reported*
At least 3
At least 4
Number of vaccine vs placebo subjects
5 vs 14
2 vs 8
95% CI Relative
Rate
0.36
Vaccine efficacy
64%
Relative
Rate
0.25
Vaccine efficacy
75%
*LRTI: Symptoms include cough, increase or change in sputum, wheezing, shortness of breath; LRTI Signs: include increased respiratory rate
0.129 – 0.987
0.053 – 1.174
15
Proportion of Group With No RSV Infection
Results: Early and Durable Protection
from RSV Infection
1.00
0.98
135 g RSV F Vaccine
0.96
Placebo
0.94
0.92
October 31, 2014
April, 15, 2015
0.90
0
50
100
150
200
Time to RSV Onset (days)
RT‐PCR confirmed RSV Events Product‐Limit Survival Estimate
Log‐Rank test or equality over strata; p=0.039
16
Results: Anti‐F Antibody Response
• Durable, 4.8‐fold increase in anti‐F IgG response
• Seroresponse in >93% of subjects2
Anti‐F IgG GMEU1 (95% CI)
6000
135 g RSV F Vaccine
5000
4000
3000
2000
Placebo
1000
0
0
10
20
30
40
50
60
Days
1geometric mean rise relative to Day 0
2% of group with EU >95th
percentile of the placebo group on that day
17
Results: Palivizumab‐competing Antibody Response
• Durable, 5.2‐fold increase in PCA response
• Seroresponse in >96% of subjects2
PCA GMC 1 (µg/mL)
120
135 g RSV F Vaccine
100
80
60
40
Placebo
20
0
0
10
20
30
40
50
60
Days
1geometric mean rise relative to Day 0
2% of group with EU >95th
percentile of the placebo group on that day
18
Geometric Mean Rise in Neutralizing Titers
(baseline adjusted) RSV A and B Microneutralizing Antibodies
2.1
RSV A
RSV B
1.9
1.7
1.5
1.3
1.1
0.9
RSV F Vaccine RSV/A
Placebo RSV F RSV/A
Vaccine RSV/A
Day 28
Placebo RSV F RSV/A
Vaccine RSV/B
Day 56
Placebo RSV F RSV/B
Vaccine RSV/B
Day 28
Placebo RSV/B
Day 56
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Efficacy of Licensed Respiratory Vaccines
• Novavax RSV F Vaccine efficacy is similar to or better than a number of respiratory vaccines1,2,3
• Influenza vaccine recommended for US population by gov’t health agencies (ACIP, CDC, other)
• Pneumococcal conjugate vaccine efficacy in older adults is 46% 1
• Published seasonal influenza vaccine effectiveness2,3 as shown in the following table: Season
Age
Vaccine Effectiveness
Age
Effectiveness
2007‐8
Overall
37% (22‐49)
≥ 50 years
37% 2009‐10
Overall
56% (23‐75)
≥ 50 years
‐5.8%*
2010‐11
Overall
60% (53‐66)
≥ 65 years
36%
2011‐12
Overall
47% (36‐56)
≥ 65 years
43%
2012‐13
Overall
49% (43‐55)
≥ 65 years
26%
2013‐14
Overall
51% (43‐58)
≥ 65 years
39% 2014‐15
Overall
23% (14‐31)
≥ 50 years
23%**
1.
Bonten, M.J.M. et al. Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults. NEJM, 2015; 372:1114‐1125.
2.
http://www.cdc.gov/flu/professionals/vaccination/effectiveness‐studies.htm
3.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6349a2.htm
* Pandemic H1N1 season ** 14% for dominant H3N2.
20
Summary
Significant disease burden due to RSV in older adults
• 4.9% of older adults had symptomatic RSV disease
• 95% of these illnesses were associated with LRTI
46% reduction in symptomatic RSV related LRTI using the vaccine
•
64% reduction in more severe illnesses
Durable protection for the entire RSV season
1
ST
First study to demonstrate effective RSV immunization
21
Annual Burden of RSV Disease in Adults 65 and Older
~14,000
~4,500,000
Deaths7
~152,000
ER Visits2, 5
Lost Productivity Days2,3
2.4M
~497,000
Infections1
Physician Visits4
~204,000
Hospital Admissions2, 5, 6
Values represent estimated annual rates
1Falsey et al NEJM, 2005; 2Falsey et al JID 2013; 3Leader et al, Value in Health, 2003; 4McClure et al., Plos One, 2014; 5Widmer et al. Influenza Other 22
Resp. Viruses, 2014; 6Widmer et al, J. Infect. Dis. 2012; 7Thompson et al., JAMA, 2003
Burden of Disease for RSV, Influenza, and
Pneumococcal Pneumonia in Adults 65 and Older
RSV
Influenza*
Pneumonia
2,400,000
2,883,052
1,286,556
Hospitalization
203,600
262,095
339,853
Deaths
14,000
14,607
22,449
Number of Infections
Deaths
# of infections
Hospitalizations
*Average of 3 past seasons, 2010‐2013; includes vaccine averted cases
CDC, Falsey et al. NEJM, 2005; Falsey et al. JID, 1995; MMWR 13 Dec 2013; Huang, et al. Vaccine, 2011; Jackson, et al. Clin Infect Dis 2004;
Reed et al. PLOS One, 2015.
23
Financial and Corporate Highlights
Novavax by the Numbers*:
Cash and Investments:
Debt:
$314.9 M
None
BARDA contract for seasonal and pandemic flu:
$179 M
Shares Outstanding:
268.0 M
Employees (approx):
356
* Novavax, Inc. August 10, 2015 10Q 24
Upcoming Development Milestones
Ongoing Trials
Q3‐14
Q4‐14
Q1‐15
Q2‐15
Q3‐15
Q4‐15
RSV Maternal Ph 2
RSV Older Adults Ph 2
RSV Pediatric Ph 1
Seasonal Flu Ph 2
Ebola Ph 1
Planned Trials
RSV/Flu Combo Ph 1
H7N9 + Matrix Ph 2
Trial Initiated
Data announced
25
Investment Highlights
Announced data from 3 of 4 clinical trials expected in the 3rd quarter
• Ebola GP Vaccine
• Quadrivalent Seasonal Influenza
• RSV F Vaccine in older adults
• RSV F Vaccine to protect infants via maternal immunization
Novavax Vaccine Platform
• Recombinant nanoparticles that induce robust and functional immunity
• Matrix‐M adjuvant that increases the magnitude and quality of immune response to certain vaccine candidates
Strong Vaccine Development Infrastructure
• Commercial GMP manufacturing capacity
• Experienced management team 26