Document text
V116: An Investigational Adult Specific Pneumococcal
Conjugate Vaccine
Key Results from the Phase 3 Clinical Development Program
ACIP Meeting, 29 -Feb -2024
Heather Platt, M.D., on behalf of the V116 team
Distinguished Scientist, Global Clinical Development
Merck Research Laboratories
Merck & Company, Inc.
Presentation Rationale for Development of V116
Overview of V116 Adult Clinical Development Program
Immunogenicity Results
•Vaccine naïve adults ≥18 years of age
•Vaccine experienced adults ≥50 years of age
Integrated Summary of Safety
•Vaccine naïve and vaccine experienced adults ≥18 years of age
Supportive Studies
•V116 in individuals living with HIV
•V116 administered with concomitant influenza vaccine
•V116 lot consistency
Conclusions
Questions
2
Confidential
The introduction of PCVs has significantly decreased disease incidence
in children and changed epidemiology of IPD in adults in the US
387.6
1.85.9
5.3
020406080100
Pre-PCV Post-PCV
PCV13 Non PCV13
*Centers for Disease Control and Prevention, IPD serotype data 2019, as compiled from data provided through Active Bacterial Core surveillance (ABCs). IPD cases per 100K in US by serotype, children <5
94
7IPD cases per 100K in US by serotype, adults ≥65
45.9
5.415.1
18.6
020406080100
Pre-PCV Post-PCV
PCV13 Non PCV1361
24
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Rationale for Development of V116
4
The burden of disease in adults remains high; IPD due to non -
vaccine serotypes has increased in adults.
V116 being developed as a population -specific vaccine to prevent invasive
disease and pneumonia in adults.
V116 is designed to complement PCV pediatric immunization
programs. PCV use in infants has significantly decreased the burden of
disease in adults through indirect protection .
Population -specific
vaccinationUnmet medical need
in adultsIndirect protection
through pediatric vaccination
Complementary to
pediatric PCVs
V116 is an adult specific pneumococcal conjugate vaccine (PCV)
IPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine; PCV13, pneumococcal conjugate vaccine, 13 -valent; PCV15 pneumococcal conjugate vaccine, 15 -valent, PCV20, pneumococcal conjugate vaccine, 20 -valent.
1. CDC , IPD Serotype Data 2019, as compiled from data provided through Active Bacterial Core surveillance (ABCs).
2. 2. Platt H , Omole T, Cardona J, Fraser NJ, Mularski RA, Andrews C, Daboul N, Gallagher N, Sapre A, Li J, Polis A, Fernsler D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21 -valent pneumococcal
conjugate vaccine, V116, in healthy adults: phase 1/2, randomised , double -blind, active comparator -controlled, multicentre , US -based trial. Lancet Infect Dis. 2023 Feb;23(2):233 -246. https://pubmed.ncbi.nlm.nih.gov/36116461/
15C is denoted here to represent the serotype protection proposed with deOAc15B as the molecular structures for deOAc15B and 15C are similar (Jones C, Lemercinier X. 2005. Full NMR assignment and revised structure for the capsular polysaccharide from
Streptococcus pneumoniae type 15B. Carbohydr Res 340:403 –409.) •Includes 21 pneumococcal serotypes , 4µg/PnPs individually conjugated to CRM197 formulated without an adjuvant
•Single dose, 0.5mL pre-filled syringe , intramuscular injection for adults 18+
•The serotypes in V116 accounted for ~85% of IPD and the 8 unique serotypes accounted for ~30% of IPD in US
adults ≥65 years in 2019
•V116 is currently under Priority Review by the FDA for the prevention of IPD and pneumonia in adults ≥18 years of
age with target action date of June 17, 2024.
Serotype Composition
PCV13 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A
PCV15 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A 22F 33F
PPSV23 4 6B 9V 14 18C 19F 23F 1 3 5 7F 19A 22F 33F 2 8 9N 10A 11A 12F 15B 17F 20
PCV20 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A 22F 33F 8 10A 11A 12F 15B
V116 3 6A 7F 19A 22F 33F 8 9N 10A 11A 12F 17F 20A 15A 15C 16F 23A 23B 24F 31 35B
5Confidential
Source: US Centers for Disease Control and Prevention, IPD serotype data 2019, as compiled from data provided through Active Bac terial Core surveillance (ABC).In adults 50 –64 and ≥65 years of age, serotypes in V116 are responsible for the
majority of residual IPD in adults
IPD coverage (% of serotypes and cases per 100,000) in US Adults 50 –64 and ≥65 years of age, 2019
38.9%55.5%67.9% 67.7%83.4%
40.2%52.9%60.2% 60.0%84.8%
PCV15 PCV20 PCV24 PPSV23 V116
PCV15 V116 PPSV23 PCV24 PCV20≥65~6 cases ~9 cases ~11 cases ~11 cases ~13 cases ~9 cases ~12 cases ~14 cases ~14 cases ~20 cases
50-64 50-64 50-64 50-64 50-64 ≥ 65 ≥ 65 ≥ 65 ≥ 65
6
V116 Phase 3 Clinical
Development Program
7
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V116 Clinical Development Program focused on enrolling participants at
risk for pneumococcal disease
8V116 -007
High Risk (HIV)
(n=300)V116 -008
At-Risk Adults
(n=900)V116 -P004
Clinical Lot Consistency
(n=2040)V116 -P003
Pivotal
(n=2600)V116 -P005
Concomitant Flu
(n=1000)V116 -P006
Vaccine Experienced
(n=700)
≥ 18 years old 18 – 64 years old18 – 49 years old ≥ 50 years old ≥ 18 years old
V116 -013
Pediatric with Increased Risk
(n=820)
≥ 2 - <18 years old
Confidential
4 Studies in the V116 BLA submission represent a broad,
diverse patient population
9V116 -007
High Risk (HIV)
(n=300)V116 -008
At-Risk Adults
(n=900)V116 -P004
Clinical Lot Consistency
(n=2040)V116 -P003
Pivotal
(n=2600)V116 -P005
Concomitant Flu
(n=1000)V116 -P006
Vaccine Experienced
(n=700)
≥ 18 years old 18 – 64 years old18 – 49 years old ≥ 50 years old ≥ 18 years old
V116 -013
Pediatric with Increased Risk
(n=820)
≥ 2 - <18 years old
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Safety Endpoints Immunogenicity Endpoints
OPA responses supported primary objectives:
•Serotype specific OPA Geometric Mean Titers (GMTs)
•Proportion of participants with ≥4-fold rise in OPA
responses from baseline to Day 30 postvaccination
OPA and IgG responses supported secondary objectives:
•Serotype specific IgG Geometric Mean Concentrations
(GMCs)
•Proportion of participants with ≥4-fold rise in IgG
responses from baseline to Day 30 postvaccination
•Geometric Mean Fold Rise (GMFR) of OPA and IgG
responses
•Reverse Cumulative Distribution Curves (RCDCs) for
OPA and IgG responsesImmunogenicity & Safety Endpoints in the V116 Program
Participants reported adverse events on an electronic vaccine report
card.Primary Safety Endpoints:
•Solicited injection site events Day 1 -5
postvaccination: erythema, swelling, injection -site
pain
•Solicited systemic events Days 1 -5 postvaccination:
headache, myalgia, fatigue
•Serious vaccine -related events Day 1 through the
duration of participation in the study
Additional Safety Endpoints:
•Unsolicited AEs, Vaccine related AEs, Any SAE
•Maximum temperature Day 1 -5 postvaccination
Immune responses were assessed in validated multiplex
opsonophagocytic (OPA) and electrochemiluminescence (ECL IgG)
assays 10
¹Weber Shandwick/KCR Research, 2020 / AMO 2019V116 -003A Phase 3, Randomized, Double -blind, Active
Comparator -controlled Clinical Study to
Evaluate the Safety, Tolerability, and
Immunogenicity of V116 in Pneumococcal
Vaccine -naïve Adults
11
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V116 -003 Study Design
V116 or PCV20
Prevaccination
Immunogenicity
(Day 1)
eVRC , solicited AEs
Serious and nonserious AEs Serious AEs
Postvaccination
Immunogenicity
(Day 30)Cohort 1 ( ≥50 years of age)
N=2362 Participants
randomized 1:1,V116 to PCV20
(Stratified by age: 50 -64, 65 -74, 75 -84, ≥85)
Cohort 2 (18 -49 years of age)
N=301 Participants
randomized 2:1,V116 to PCV20
Immunogenicity
assessment
Safety
assessmentDay 1 Day 5 Day 7 Day 90 Day 30 Month 6Pivotal Study
1 3 2 4 5
12
V116 -003: Primary study objectives
Primary safety Primary immunogenicity
In adults ≥50 years:
•Demonstrate that V116 is noninferior to PCV20 for
10 common serotypes
–Lower bound of the 2 -sided 95% CI of the OPA GMT ratio
(V116/PCV20) to be >0.5
•Demonstrate that V116 is superior to PCV20 for
11 unique serotypes
–Lower bound of the 2 -sided 95% CI of the OPA GMT ratio
(V116/PCV20) to be >2.0
–2-sided 95% CI of the differences (V116 – PCV20) between the
proportions of participants with a ≥4-fold rise to be >10%
In adults 18 –49 years:
•Demonstrate V116 immunobridges to adults 50 -64
years of age for 21 serotypes in V116
–Lower bound of the 2 -sided 95% CI of the OPA GMT ratio
(V116 18 -49/V116 50 –64 years ) to be >0.5•To evaluate the safety and tolerability of V116 as
assessed by the proportion of participants with adverse
events (AEs)
–Solicited injection site events Day 1 –5 postvaccination:
erythema, swelling, injection -site pain
–Solicited systemic events Days 1–5 postvaccination:
headache, myalgia, fatigue
–Serious vaccine -related events Day 1 through the duration of
participation in the studyPivotal Study
13
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V116 -003 Baseline Characteristics
In each cohort, baseline characteristics were balanced between the treatment groups
Risk Factors includes prespecified medical history conditions: Alcoholism, Chronic Heart Disease, Chronic Kidney Disease, Chr onic Liver Disease, Chronic Lung Disease, Diabetes, Smoking.14Cohort 1 (Age ≥50 years) Cohort 2 (Ages 18 -49 years)
V116, N=1179 PCV20, N=1177 V116, N=200 PCV20, N=100
Sex
Female 687 (58.3) 670 (56.9) 137 (68.5) 64 (64.0)
Age ( yr)
Median (min to max) 65 (50 -91) 65 (50 -97) 36 (18 -49) 34 (18 -49)
18-49, n (%) 0 (0) 0 (0) 200 (100) 100 (100)
50 to 64, n (%) 589 (50.0) 587 (49.9) 0 (0) 0 (0)
65 to 74, n (%) 464 (39.4) 464 (39.4) 0 (0) 0 (0)
75-84, n (%) 112 (9.5) 113 (9.6) 0 (0) 0 (0)
≥85, n (%) 14 (1.2) 13 (1.1) 0 (0) 0 (0)
Race
Asian 148 (12.6) 168 (14.3) 38 (19.0) 15 (15.0)
Black or African American 116 (9.8) 115 (9.8) 13 (6.5) 14 (14.0)
Multiple 26 (2.2) 30 (2.5) 9 (4.5) 6 (6.0)
White 867 (73.5) 844 (71.7) 139 (69.5) 62 (62.0)
Other 21 (1.8) 19 (1.6) 1 (0.5) 3 (3.0)
Ethnicity
Hispanic or Latino 259 (22.0) 242 (20.6) 58 (29.0) 24 (24.0)
Pneumococcal Risk Factors
1 Risk Factor 347 (29.4) 328 (27.9) 45 (22.5) 18 (18.0)
2 or More Risk Factors 100 (8.5) 81 (6.9) 3 (1.5) 1 (1.0)Pivotal Study
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Pneumococcal
serotypeV116 PCV20 GMT ratio
n GMT n GMT (95% CI)
3 1154 274.0 1161 176.7 1.55 (1.40, 1.72)
6A 1148 2,302.0 1153 2,972.5 0.77 (0.68, 0.88)
7F 1152 3,637.4 1158 3,429.9 1.06 (0.95, 1.18)
8 1155 2,501.3 1158 1,811.1 1.38 (1.25, 1.53)
10A 1161 3,893.4 1159 4,678.0 0.83 (0.75, 0.93)
11A 1145 3,232.6 1150 2,092.8 1.54 (1.39, 1.72)
12F 1160 2,641.2 1161 2,499.6 1.06 (0.92, 1.21)
19A 1159 2,136.1 1162 2,817.8 0.76 (0.69, 0.84)
22F 1147 3,874.5 1154 4,770.1 0.81 (0.72, 0.92)
33F 1154 13,558.9 1157 11,742.1 1.15 (1.01, 1.32)•V116 is noninferior to PCV20
for the 10 common serotypes.
•The lower bounds of the two -
sided 95% confidence
intervals (CIs) are greater
than 0.5 for all 10 common
serotypes.Primary immunogenicity objectiveV116 -003 Cohort 1: ≥50 years of age
V116 is noninferior to PCV20 for the 10 common serotypes
Postvaccination OPA GMT Ratios for Common Serotypes
0.5 1.0 2.0
GMT ratio log10 scale (V116/PCV20)
15Pivotal Study
Confidential
•V116 is superior to PCV20 for
10 of 11 unique serotypes in
V116.
•The lower bounds of the two -
sided 95% CIs are >2.0 for 10
of 11 unique serotypes in V116.
•For serotype 15C, the lower
bound of the 95% CI is 1.77.Primary immunogenicity objectivePostvaccination OPA GMT Ratios for Unique Serotypes
Pneumococcal
serotypeV116 PCV20 GMT ratio
n GMT n GMT (95% CI)
9N 1147 7,470.7 1150 1,640.4 4.55 (4.12, 5.04)
15A 1107 5,237.2 1102 1,589.0 3.30 (2.91, 3.74)
15C 1153 4,216.2 1158 2,072.3 2.03 (1.77, 2.34)
16F 1151 4,868.2 1153 846.3 5.75 (5.16, 6.41)
17F 1148 7,764.9 1156 460.4 16.86 (14.90, 19.09)
20A 1161 6,099.2 1155 631.1 9.66 (8.66, 10.79)
23A 1132 3,737.2 1104 461.5 8.10 (6.86, 9.55)
23B 1160 1,082.5 1160 107.3 10.09 (8.48, 12.00)
24F 1153 2,728.6 1130 70.5 38.71 (33.87, 44.25)
31 1153 3,132.5 1154 144.4 21.69 (18.68, 25.18)
35B 1153 8,527.8 1159 1,383.0 6.17 (5.59, 6.80)
GMT ratio log10 scale (V116/PCV20)1 0.5 2 4 8 16 32 64V116 -003 Cohort 1: ≥50 years of age
V116 is superior to PCV20 for 10 of 11 unique serotypes
16Pivotal Study
Superiority criteria met if the lower bound of the 95% CI is >2.0
Confidential
•V116 is superior to PCV20
for 10 of 11 unique
serotypes in V116.
•The lower bounds of the
2-sided 95% CIs are > 10
percentage points for 10
of 11 serotypes.Primary immunogenicity objectiveProportions of Participants With a ≥4-Fold Rise in OPA
Responses for Unique Serotypes64.7%
66.7%
83.4%
71.9%
75.8%
67.3%
78.9%
85.5%
80.5%
76.5%
60.0%19.9%
35.8%
74.2%
20.8%
9.5%
9.6%
36.8%
49.6%
6.3%
17.9%
6.8%
0%20%40%60%80%100%
9N 15A 15C 16F 17F 20A 23A 23B 24F 31 35B% of participants with a ≥4-fold rise
Unique serotype
V116 (N=1179) PCV20 (N=1177)44.7% 30.9% 9.2% 51.1% 66.3% 57.7% 42.2% 35.9% 74.2% 58.6% 53.2%% difference [V116 – PCV20]
p=0.665(40.7. 48.6) (25.8, 35.8) (5.6, 12.9) (47.1, 54.9) (62.8, 69.6) (54.2, 61.1) (37.6, 46.6) (32.1, 39.6) (71.1, 77.1) (54.8, 62.1) (49.6, 56.6) V116 -003 Cohort 1: ≥50 years of age
V116 is superior to PCV20 for 10 of 11 unique serotypes
17Pivotal Study
Confidential
V116 -003 Cohort 1: ≥50 years of age
V116 elicits robust cross reactive antibody responses to serotype 15B
18V116 includes serotype 15C
and elicited cross -reactive
immune responses to 15B0%20%40%60%80%100%
V116 (N=1179) PCV20 (N=1177)% of participants with a ≥4-fold rise in OPA
responsesSerotype 15BPivotal Study
PCV20 includes
serotype 15B64.6%
(61.3, 67.8) 64.7%
(61.4, 67.8)
Confidential
•V116 in participants 18 to 49
years of age immunobridges
to V116 in participants 50 to
64 years of age for the 21
serotypes in V116.
•The lower bound of the two -
sided 95% CIs is >0.5 for all
21 serotypes in V116.Primary immunogenicity objective
Pneumococcal
serotypeV116
18–49 years
(N = 200)V116
50–64 years
(N = 589)GMT ratioa
(V116 18 –49 years/
V116 50–64 years)
n GMT n GMT (95% CI)
3 194 308.6 572 282.7 1.09 (0.90, 1.33)
6A 196 5,289.6 569 2,572.9 2.06 (1.61, 2.62)
7F 198 6,447.2 571 4,278.8 1.51 (1.23, 1.84)
8 197 4,516.0 571 3,004.7 1.50 (1.26, 1.79)
9N 197 17,283.2 570 8,791.4 1.97 (1.59, 2.43)
10A 197 6,808.1 575 4,382.6 1.55 (1.26, 1.92)
11A 196 5,871.6 564 3,785.8 1.55 (1.26, 1.91)
12F 196 6,150.4 574 3,561.2 1.73 (1.37, 2.17)
15A 184 11,319.2 550 5,901.2 1.92 (1.55, 2.37)
15C 195 10,194.0 570 5,708.0 1.79 (1.36, 2.35)
16F 193 8,877.0 571 5,720.0 1.55 (1.26, 1.91)
17F 194 16,070.6 568 10,068.0 1.60 (1.26, 2.02)
19A 198 2,773.2 574 2,374.6 1.17 (0.97, 1.40)
20A 197 13,150.0 575 7,562.7 1.74 (1.39, 2.18)
22F 198 9,299.6 568 4,683.6 1.99 (1.58, 2.49)
23A 192 8,848.7 561 4,739.5 1.87 (1.43, 2.44)
23B 198 2,140.1 575 1,420.9 1.51 (1.11, 2.04)
24F 197 4,137.6 570 3,047.2 1.36 (1.10, 1.67)
31 195 8,005.6 570 3,820.7 2.10 (1.63, 2.69)
33F 197 34,805.5 570 17,607.4 1.98 (1.52, 2.57)
35B 198 13,933.4 573 9,053.9 1.54 (1.26, 1.87)
GMT ratio log10 scale (V116 18 -49/V116 50 -64)1 0.5 2 4V116 -003: Cohort 2: 18-49 years of age
V116 immunobridges to participants 50 -64 years of age for all 21 serotypes
19Pivotal Study
¹Weber Shandwick/KCR Research, 2020 / AMO 2019V116 -006V116 -006: A Phase 3 Clinical Study to Evaluate
the Safety, Tolerability, and Immunogenicity of
V116 in Pneumococcal Vaccine -Experienced
Adults 50 Years of Age or Older
20
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Cohort 1 : Prior PPSV23 only
N=300; Randomized 2:1 (V116:PCV15)V116 -006 Study Design
Visit
Time Day 1
Screening/vaccination1 3
V116Day 7 Day 90 Day 1802 4 5
Cohort 2 : Prior PCV13 only
N=300; Randomized 2:1 (V116:PPSV23)
Cohort 3 : Prior PCV15, PCV20, PCV13+PPSV23,
PCV15+PPSV23 or PPSV23+PCV13
N=100; Open -label V116Day 30
V116V116or
orPCV15
PPSV23
Prevaccination
Immunogenicity
(Day 1)
eVRC , solicited AEs
Serious and nonserious AEs Serious AEs
Postvaccination
Immunogenicity
(Day 30)
Participants used an electronic Vaccine Report Card ( eVRC ) to report solicited AEs Days 1 -5 postvaccination and other AEs through Day 30 postvaccination21Vaccine -experienced
Immunogenicity
assessment
Safety
assessment
Confidential
In adults ≥50 years:
To evaluate the serotype -specific opsonophagocytic activity
(OPA) geometric mean titers (GMTs) at 30 days postvaccination
for all serotypes included in V116V116 -006 Primary study objectivesVaccine -experienced
Primary safety Primary immunogenicity
•To evaluate the safety and tolerability of V116 as
assessed by the proportion of participants with adverse
events (AEs)
–Solicited injection site events Day 1 –5 postvaccination:
erythema, swelling, injection -site pain
–Solicited systemic events Days 1–5 postvaccination:
headache, myalgia, fatigue
–Serious vaccine -related events Day 1 through the duration of
participation in the study
22
Confidential
V116 -006 Participant Characteristics
Enrollment is balanced in each cohort and reflects the pneumococcal vaccination history
23Cohort 1 (prior PPSV23) Cohort 2 (prior PCV13) Cohort 3
V116
N=229PCV15
N=119V116
N=174PPSV23
N=85V116
N=105
Sex
Male 112 (48.9) 59 (49.6) 74 (42.5) 36 (42.4) 50 (47.6)
Female 117 (51.1) 60 (50.4) 100 (57.5) 49 (57.6) 55 (52.4)
Age ( yr)
50 to 64 48 (21.0) 25 (21.0) 80 (46.0) 39 (45.9) 17 (16.2)
≥65 181 (79.0) 94 (79.0) 94 (54.0) 46 (54.1) 88 (83.8)
Mean ±SD 68.7 ±7.5 69.0 ±7.1 65.5 ±7.8 65.4 ±6.6 71.0 ±7.6
Median (range) 69.0 (50 to 86) 69.0 (51 to 88) 66.0 (50 to 83) 65.0 (51 to 81) 71.0 (53 to 91)
Race
Asian 96 (41.9) 47 (39.5) 55 (31.6) 25 (29.4) 13 (12.4)
Black or African American 6 (2.6) 3 (2.5) 3 (1.7) 1 (1.2) 6 (5.7)
Multiple 2 (0.9) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.0)
White 125 (54.6) 69 (58.0) 116 (66.7) 59 (69.4) 85 (81.0)
Ethnicity
Hispanic or Latino 21 (9.2) 17 (14.3) 34 (19.5) 16 (18.8) 14 (13.3)
Time since last pneumococcal
vaccination
1 to 4 years 108 (47.2) 54 (45.4) 135 (77.6) 66 (77.6) 78 (74.3)
5 to 9 years 85 (37.1) 45 (37.8) 33 (19.0) 18 (21.2) 27 (25.7)
≥10 years 36 (15.7) 20 (16.8) 6 (3.4) 1 (1.2) 0 (0.0)Vaccine -experienced
Confidential
V116 -006 Cohort 1: ≥50 years of age who previously received PPSV23
V116 elicits comparable immune responses to PCV15; higher immune responses for serotypes unique to V116
2402,0004,0006,0008,000
8 9N 10A 11A 12F 15A 15C 16F 17F 20A 23A 23B 24F 31 35BObserved GMTUnique serotypes
V116 (N=229) PCV15 (N=119)02,0004,0006,0008,000
3 6A 7F 19A 22F 33FObserved GMTCommon serotypes
V116 (N=229) PCV15 (N=119)Vaccine -experienced
Confidential
V116 -006 Cohort 2: ≥50 years of age who previously received PCV13
V116 elicits comparable immune responses to PPSV23; higher immune responses for serotypes unique to V116
2502,5005,0007,50010,00012,500
3 7F 8 9N 10A 11A 12F 17F 19A 20A 22F 33FObserved GMTCommon serotypes
V116 (N=174) PPSV23 (N=85)02,5005,0007,50010,00012,500
6A 15A 15C 16F 23A 23B 24F 31 35BObserved GMTUnique serotypes
V116 (N=174) PPSV23 (N=85)Vaccine -experienced
Confidential
*Prior PCV13+PPSV23 [n=45], PCV15+PPSV23 [n=5], PPSV23+PCV13 [n=54], PCV15 [n=1], or PCV20 [n=0] 02,0004,0006,0008,000
3 6A 7F 8 9N 10A 11A 12F 15A 15C 16F 17F 19A 20A 22F 23A 23B 24F 31 33F 35BObserved GMT
05001,000
Serotype 3Observed GMTcohort 1 cohort 2 cohort 3V116 -006 Cohort 3: ≥50 years of age who previously received other pneumococcal vaccine(s)*
V116 is immunogenic in individuals who previously received a pneumococcal vaccine
26Participants who received V116Vaccine -experienced
Integrated Summary of Safety
27Integrated Analysis of Safety in the
Phase 3 Clinical Development Program
Confidential
V116 is well tolerated in adults ≥18 years of age with a safety profile comparable to
currently licensed pneumococcal vaccines
28a Only participants from V116 -005 vaccinated with V116 in the sequential group are included in the V116 group.
bControl group includes participants vaccinated with PCV15, PCV20, or PPSV23
cAs determined by the investigator; all injection site adverse events are assessed as vaccine -related
d6 deaths in the V116 group in the Integrated Safety Summary; 7 deaths in the V116 group across the Phase 3 studies when the c oncomitant group from P005 is included. Adverse Event Summary
(V116 -003, V116 -004, V116 -005a, V116 -006) V116
(N=4,020)Control b
(N=2,018)
n (%) n (%)
With adverse events (Day 1 –30) 2695 (67.0) 1386 (68.7)
With vaccine -related adverse events (Day 1 -30)c2555 (63.3) 1297 (64.3)
Solicited 2516 (62.6) 1279 (63.4)
Unsolicited 313 (7.8) 123 (6.1)
with SAEs (Day 1 -Day 30) 14 (0.3) 7 (0.3)
with vaccine -related SAEs (Day 1 -Day 30) 2 (0.0) 0 (0.0)
with SAEs within 30 minutes postvaccination 1 (0.0) 0 (0.0)
Who diedd6 (0.1) 3 (0.1)
with vaccine -related deathsc0 (0.0) 0 (0.0)Integrated Safety
Solicited events include erythema, injection site pain, injection site swelling, fatigue, headache, and myalgia were solicite d from Day 1 through Day 5 postvaccination. Pyrexia was defined as
temperature ≥100.4 °F (38.0 C) solicited from Day 1 through Day 5 postvaccination.Frequency and intensity of solicited adverse events were comparable in V116 and control groups
Solicited adverse events by intensity (%)
0%10%20%30%40%50%60%
V116 Control V116 Control V116 Control V116 Control V116 Control V116 Control V116 ControlPotentially Life-threatening (Grade 4)
Severe (Grade 3)
Moderate (Grade 2)
Mild (Grade 1)
Injection site
erythemaInjection site pain Injection site
swellingFatigue Myalgia Headache PyrexiaIntegrated Safety
V116, n= 4,020 Control, n=2,018Majority of events were
≤3 days in duration
29
Phase 3 Supportive Studies
30V116 -007: V116 in Adults Living with HIV
V116 -005: V116 with Concomitant Quadrivalent Influenza Vaccine (QIV)
V116 -004: V116 Lot Consistency
Confidential
02,0004,0006,0008,00010,00012,00014,000
15A 15C 16F 23A 23B 24F 31 35BObserved GMTUnique serotypes
V116 + Placebo (N = 156) PCV15 + PPSV23 (N = 156)04,0008,00012,00016,00020,000
3 6A 7F 8 9N 10A 11A 12F 17F 19A 20A 22F 33FObserved GMTCommon serotypes
V116 + Placebo (N = 156) PCV15 + PPSV23 (N = 156)V116 -007: In adults living with HIV, V116 elicits comparable immune responses
to PCV15+PPSV23, & higher immune responses for unique serotypesAdults Living with HIV
31
Confidential
V116 -005: V116 elicits robust immune responses when administered
concomitantly with influenza vaccine
32•V116 administered
concomitantly with influenza
vaccine is noninferior to V116
administered sequentially
with influenza vaccine for 20
of 21 serotypes
•QIV administered
concomitantly is noninferior
to QIV administered
sequentially for 3 of 4 strains GMT ratio
Concomitant/Sequential
(95% CI)Pneumococcal
serotype
3 0.84 (0.72, 0.97)
6A 0.79 (0.66, 0.94)
7F 0.73 (0.63, 0.85)
8 0.71 (0.61, 0.82)
9N 0.67 (0.57, 0.79)
10A 0.76 (0.65, 0.91)
11A 0.64 (0.54, 0.75)
12F 0.76 (0.62, 0.94)
15A 0.71 (0.60, 0.85)
15C 0.71 (0.58, 0.87)
16F 0.69 (0.59, 0.81)
17F 0.73 (0.62, 0.86)
19A 0.75 (0.65, 0.85)
20A 0.74 (0.63, 0.87)
22F 0.77 (0.65, 0.91)
23A 0.78 (0.63, 0.96)
23B 0.56 (0.44, 0.72)
24F 0.72 (0.61, 0.86)
31 0.68 (0.56, 0.83)
33F 0.84 (0.70, 1.01)
35B 0.77 (0.67, 0.89)
0.25 0.5 1 2
GMT Ratio Log10 Scale
(Concomitant Group/Sequential Group)Concomitant Influenza
32
Confidential
V116 -004: V116 Immune responses were equivalent across 3 manufacturing lots
33Pneumococcal
serotypeV116 Lot 1 vs V116 Lot 2
n1=(502 -527), n2=(505 -533)V116 Lot 1 vs V116 Lot 3
n1=(502 -527), n2=(513 -533)V116 Lot 2 vs V116 Lot 3
n1=(505 -533), n2=(513 -533)
3
6A
7F
8
9N
10A
11A
12F
15A
15C
16F
17F
19A
20A
22F
23A
23B
24F
31
33F
35B
0.5 2 0.5 2 0.5 2 1 1 1
GMT Ratio Log10 Scale
Note: dashed lines indicate the margins for the equivalence testLot Consistency
Phase 3 Summary &
Conclusions
34
Confidential
V116 Phase 3 Clinical Development Summary
35In adults ≥18 years of age, who are pneumococcal vaccine -naïve and vaccine
experienced, with and without risk conditions:
•V116 elicits robust immune responses to all 21 serotypes contained in the vaccine
•V116 is noninferior to PCV20 for all common serotypes and superior to PCV20 for 10 of 11
serotypes unique to V116 in pneumococcal vaccine -naïve adults ≥50 years of age.
•V116 is immunogenic in pneumococcal vaccine experienced adults , regardless of the prior
vaccine received
•V116 is immunogenic when administered concomitantly with inactivated influenza vaccine .
•V116 is well -tolerated with a safety profile generally comparable to currently licensed
pneumococcal vaccines.
V116 is the first adult specific PCV with the potential for broad public health impact through the prevention of invasive dis ease
and pneumonia due to S. pneumoniae .
Confidential
Thank you
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