125742 S1 M2 2.6.7.1toxicology tabulated summary

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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.1 Toxicology:  Overview Test Article: BNT162b2
Type of Study Species/
StrainMethod of 
Administratio nDuration of
DosingDose
(µgRNA/anim al)Total Volum e
(µL)aGLP
ComplianceTesting 
FacilityStudy 
Number 
(Sponsor 
Reference 
Number)
Single-Dose Toxicity
Not conducted
Repeat-Dose Toxicity
17-Day,
2-or 3-Dose
(1Dose/Week)
Toxicity With a
3-Week Recovery 
PhaseRat/
Wistar HanIM Injection 17Days
(Dose days
1, 8, 15)
or
10Days
(Dose days
1, 8)b0
(Control Bufferc)
30
(BNT162a1)
10
(BNT162a1)
30
(BNT162b1)
100
(BNT162b1)
30
(BNT162c1)
100
(BNT162b2 [V8])200d
60
20
60
200d
70
200dYes 38166
(NA)
17-Day, 3-Dose
(1Dose/Week)
Toxicity With a
3-Week Recovery 
PhaseRat/
Wistar HanIM Injection 17Days
(Dose days
1, 8, 15)0
(Saline)f
30
(BNT162b2 [V9])
30
(BNT162b3)60
60
60Yes PWRDg20GR142
(NA)
Genotoxicity
Not conducted
Carcinogenicity
Not conducted
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.1 Toxicology:  Overview Test Article:  BNT162b2 (continued)
Type of Study Species/
StrainMethod of 
AdministrationDuration of
DosingDose
(µgRNA/anim al)Total Volum e
(µL)aGLP
ComplianceTesting 
FacilityStudy 
Number 
(Sponsor 
Reference 
Number)
Reproductive and Developmental Toxicity
Combined 
Fertility and
Developmental 
(Including 
Teratogenicity
and Postnatal 
Investigations)Rat/
Wistar HanIM Injection 21 and 14 days 
prior to mating, 
GD9, GD200
(Saline)f
30
(BNT162b1)
30
(BNT162b2 [V9]),
30
(BNT162b3)60
60
60
60Yes Charles River 
Laboratoriesh20256434
(RN9391
R58)
Local Tolerance
Not conducted
Other Toxicity Studies
Not conducted
GD=Gestation day; GLP =Good Laboratory Practice; IM =Intramuscular; ; NA=Not applicable; 
PWRD=Pfizer Worldwide Research & Development; QW =Once weekly.
a. Doses w ere administered as 1 application at 1 site unless otherwise indicated.
b. QWx3 (Days 1, 8, 15) for BNT162a1, BNT162b1, and BNT162b2 (V8); QWx2 (Days 1, 8) for BNT162c1.
c. Phosphate buffered saline, 300 mM sucrose.
d. One application (100 µL) at 2 sites for a total dose volume of 200 µL.
f. Sterile saline (0.9% NaCl).
g. Groton, CT, US.
h. Saint-Germain-Nuelles,France.
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Report Title:  Repeat -Dose Toxicity Study 
of Three LNP -Formulated RNA 
Platforms Encoding for Viral 
Proteins by Repeated 
Intramuscular Administration to 
Wistar Han RatsTest Article: BNT162b2
Species/Strain:  Rat/Wistar Han Duration of Dosing:  QWx3 (Days 1, 8, 15) for Study Number:  38166a
BNT162a1 (uRNA-LNP RBD ), BNT162b1 (modRNA-Lot Numbers:   CoVVAC/090320 (BNT162a1 ),
LNP RBD), or BNT162b2 [V8](modRNA-LNP SP2 );
QWx2(Days1, 8) for BNT162c1 (saRNA-LNP RBD )CoVVAC/100320 ( BNT162b1 ), CoVVAC/130320
(BNT162c1 ), CoVVAC/160320 ( BNT162b2 [V8])
Age at First Dose :~8-9 Weeks Duration of Postdose:  3Weeks GLP Compliance:  Yes
Date of First Dose:   17March2020 Method of Adm inistration:  Intramuscular injection;
20 to 100 µL/administration site/doseb
Vehicle/Formulation:   Phosphate buffered sal ine, 300mM sucrose /Solution
Special Features:   Cytokine analysis (IFN-, TNF-, IL-1, IL-6, IL-10)
No Observed Adverse Effect Level:   30µg (BNT162a1, BNT162c1), 100 µg (BNT162b1, BNT162b2)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing Day 2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Number of Animalsc15 15 15 15 15151515151515151515
Noteworthy Findings
Died or Euthanized Moribund 0 0 0 0 0000000000
Body Weight(g)d
Prior to Initiation of Dosing 257.6 213.8 1.0 1.0 1.00.891.01.01.00.90 1.00.911.00.90
Day1 263.5 212.3 0.99 0.99 1.2†1.01.01.01.2†1.01.2†1.01.2†1.0
Day2 268.9 215.1 0.93†0.95 1.1†0.980.95†1.01.00.951.1†0.981.00.96
Day8 310.9 231.7 0.94†0.99 1.1†1.00.981.01.01.01.00.991.00.98
Day9 319.8 237.0 0.87†0.931.00.950.930.99 0.93 †0.940.96 0.93 †0.92†0.93
Day15 356.3 249.8 0.88†0.97 1.00.980.951.00.98 0.99 0.98e0.95e0.96 0.95
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Body Weight Gain (%)f
Day 9 21.3 11.7 6.3 5.82.94.313.6 9.5-3.53.6-0.771.5-4.11.2
Day 16 37.1 16.7 15.1 10.011.911.025.217.1 6.010.3 NANA4.86.4
Food Consumptiond–
Relative
(g/kg of body weight/day)
Week 1 95.0 98.3 0.940.97 0.83 †0.930.96 0.98 0.77 †0.87†0.81†0.90†0.78†0.86†
Week 2 89.4 94.3 0.93†0.960.90†0.990.98 1.00.88†0.980.86†e0.98e0.89†0.98
Clinical Observations - - - -----------
Local Toleranc eg
Day1 –Edema
4Hours Postdose - - - -----------
24Hours Postdose
Edema, very slight 0 0 6 196654911101211
Edema, slight 0 0 2 00026000000
48Hours Postdose
Edema, very slight 0 0 4 7 13 9 8 6 7 6 10 10 8 2
Edema, slight 0 0 3 50026003100
96Hours Postdose
Edema, very slight 0 0 3 30010000200
144Hours Postdose - - - -----------
Day8 –Edema 
4Hours Postdose
Edema, very slight 0 0 0 00100000000
24Hours Postdose
Edema, very slight 0 0 3 2351113 764978
Edema, slight 0 0 7 90131000000
Edema, moderate 0 0 4 30000000000
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
48Hours Postdose
Edema, very slight 0 0 3 00089100003
Edema, slight 0 0 7 76820850166
Edema, moderate 1 1 4 79721610 3496
Edema, severe 0 0 0 00000002000
96Hours Postdose
Edema, very slight 0 0 8 94140000300
Edema, slight 0 0 1 21000000000
144Hours Postdose
Edema, very slight 0 0 0 02000000000
192 Hours Postdose
Edema, slight 0 0 0 00000001000
240 Hours Postdose NA NA NA NANANANANANANA --NANA
Day15–Edema 
4Hours Postdose - - - -------NANA --
24Hours Postdose
Edema, very slight 0 0 3 610 810 700NANA 00
Edema, slight 0 0 12 93758912NANA 12
Edema, moderate 0 0 0 0000063NANA 1212
Edema, severe 0 0 0 0000000NANA 21
48 Hours Postdose
Edema, very slight 0 0 1 1112300NANA 01
Edema, slight 0 0 3 4243214NANA 13
Edema, moderate 0 0 0 0000041NANA 41
96 Hours Postdose
Edema, very slight 0 0 1 2100032NANA 31
Edema, slight 0 0 2 3100000NANA 23
144 Hours Postdose
Edema, very slight 0 0 1 0100032NANA 32
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Edema, slight 0 0 0 0100000NANA 22
192 Hours Postdose - - - -----------
240 Hours Postdose
Edema, very slight 0 0 0 1232234NANA 13
Edema, slight 0 0 0 0000011NANA 42
288 Hours Postdose
Edema, very slight 0 0 0 1202145NANA 34
Edema, slight 0 0 0 0000000NANA 21
336 Hours Postdose
Edema, very slight 0 0 0 0000020NANA 00
384 Hours Postdose
Edema, very slight 0 0 0 0000020NANA 00
432 Hours Postdose
Edema, very slight 0 0 0 0000010NANA 00
480 Hours Postdose
Edema, very slight 0 0 0 0000010NANA 00
528 Hours Postdose - - - -------NANA --
Day1 –Erythem a 
4Hours Postdose - - - -----------
24Hours Postdose - - - -----------
48Hours Postdose
Erythema, very slight 0 0 0 00000030000
96Hours Postdose
Erythema, very slight 0 0 9 71000023402
144Hours Postdose - - - -----------
Day8 –Erythem a 
4Hours Postdose - - - -----------
24Hours Postdose
Erythema, very slight 0 0 6 50041000000
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
48Hours Postdose
Erythema, very slight 0 0 7 90011000000
Erythema, well defined 0 0 2 10000000000
96Hours Postdose
Erythema, very slight 0 0 3 10000000000
144Hours Postdose
Erythema, severe 0 0 0 05400034235
192 Hours Postdose NA NA NA NANANANANANANA --NANA
240 Hours Postdose
Erythema, severe NA NA NA NANANANANANANA 10NANA
288Hours Postdose
Erythema, severe NA NA NA NANANANANANANA 10NANA
336Hours Postdose
Erythema, severe NA NA NA NANANANANANANA 10NANA
384Hours Postdose
Erythema, severe NA NA NA NANANANANANANA 10NANA
432Hours Postdose
Erythema, very slight NA NA NA NANANANANANANA 10NANA
480Hours Postdose
Erythema, very slight NA NA NA NANANANANANANA 10NANA
528Hours Postdose
Erythema, very slight NA NA NA NANANANANANANA 10NANA
Day15–Erythem a 
4Hours Postdose - - - -------NANA --
24Hours Postdose
Erythema, very slight 0 0 1 2111201NANA 00
48 Hours Postdose
Erythema, very slight 0 0 2 1311000NANA 12
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
96 Hours Postdose
Erythema, severe 0 0 5 5000000NANA 00
144 Hours Postdose
Erythema, very slight 0 0 3 1000000NANA 00
Erythema, well -defined 0 3000000NANA 00
192 Hours Postdose
Erythema, very slight 0 0 0 1000000NANA 00
Erythema, severe 2 2000000NANA 00
240 Hours Postdose
Erythema, severe 0 0 2 2000000NANA 00
288 Hours Postdose
Erythema, severe 0 0 2 2000000NANA 00
336 Hours Postdose
Erythema, very slight 0 0 2 0000000NANA 00
Erythema, severe 0 0 0 2000000NANA 00
384 Hours Postdose
Erythema, very slight 0 0 2 0000000NANA 00
Erythema, severe 0 0 0 2000000NANA 00
432 Hours Postdose
Erythema, very slight 0 0 2 0000000NANA 00
Erythema, well -defined 0 0 0 2000000NANA 00
480 Hours Postdose - - - -------NANA --
Day 1 –I/Hh- - - -----------
Day8 –I/H
4Hours Postdose - - - -----------
24Hours Postdose - - - -----------
48Hours Postdose - - - -----------
96Hours Postdose - - - -----------
144Hours Postdose
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
I/H, slight 0 0 0 01000000000
Day15–I/Hh- - - -------NANA --
4Hours Postdose - - - -------NANA --
24Hours Postdose - - - -------NANA --
48Hours Postdose
I/H, very slight 0 0 0 0100000NANA 00
96Hours Postdose - - - -------NANA --
144Hours Postdose - - - -------NANA --
192 Hours Postdose
I/H, moderate 0 0 0 0100000NANA 00
240 Hours Postdose - - - -------NANA --
288 Hours Postdose - - - -------NANA --
336 Hours Postdose
1/H, slight 0 0 0 0001000NANA 00
384 Hours Postdose
I/H, very slight 0 0 0 0001000NANA 00
432 Hours Postdose
I/H, very slight 0 0 0 0001000NANA 00
480 Hours Postdose - - - -------NANA --
Ophthalmology - - - -----------
Auditory - - - -----------
Body temperature (C)
Day1
4Hours Postdose 37.4 37.4 37.9† 38.3† 37.738.2† 37.6 37.7 38.7† 38.4† 38.3† 38.7† 38.5† 38.5†
24Hours Postdose 37.5 38.3 38.5† 38.637.038.437.838.536.7† 38.336.6† 38.137.539.1†
Day8
4Hours Postdose 37.3 37.6 37.9† 38.4† 37.6 38.0 37.5 38.2 38.0†38.238.0† 38.4† 38.1† 38.4†
24Hours Postdose 37.3 38.4 39.0† 39.038.038.838.2† 38.739.0† 39.039.0† 39.038.9†39.3†
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Day15
4Hours Postdose 38.3 38.9 38.2 38.7 37.6† 38.937.4† 37.6† 38.739.238.6e38.7e38.6 39.1
24Hours Postdose 38.0 39.0 38.9† 39.238.239.138.039.039.1† 39.4 NANA39.1†39.5*
Hematology/Coagulationi
Red Blood Cell (106/µL)
Day4 7.270 7.654 7.218 7.2957.754† 7.8077.1267.5067.784† 7.5897.796† 7.5767.848† 7.578
Day10 NA NA NA NANANANANANANA7.7087.419 NANA
Day17 7.956 7.892 7.723 7.5467.8447.465* 7.7517.248† 7.5117.145† NANA7.6707.115†
Hemoglobin (mmol/L)
Day4 8.60 8.87 8.43 8.578.99* 9.128.21* 8.708.93* 8.628.95* 8.789.11† 8.74
Day10 NA NA NA NANANANANANANA8.758.43NANA
Day17 9.14 9.08 8.67† 8.668.69†8.38†8.62†8.13†8.14†7.85† NANA8.31†7.93†
Hematocrit (%)
Day4 41.92 41.87 40.58 40.4142.7742.2340.39* 41.3942.5340.4942.6640.3142.8840.15
Day10 NA NA NA NANANANANANANA41.4638.86 NANA
Day17 45.03 43.45 42.43† 41.7441.10†39.24†42.66†39.50†38.79†37.06† NANA39.65†37.59†
Reticulocytes (103/µL)
Day4 307.0 195.7 74.9† 69.8† 116.3† 94.9†171.1†143.9112.5† 112.3† 77.1† 79.6† 85.5† 101.3†
Day10 NA NA NA NANANANANANANA192.7184.4 NANA
Day17 234.6 201.0 174.8† 199.8190.4225.5188.6209.9 223.3 226.7 NA NA 172.9† 198.0
Platelets ( 103/µL)
Day10 NA NA NA NANANANANANANA708.8570.4 NANA
Day17 1089.2 1068.1 804.7† 622.9† 805.1† 698.1† 930.6876.8817.2† 702.2† NA NA 771.4†704.4†
White blood cells (103/µL)
Day4 9.37 8.42 11.7512.89† 10.57 8.7210.00 8.3110.91 9.0512.89† 10.0312.83† 10.40
Day10 NA NA NA NANANANANANANA20.1215.27 NANA
Day17 9.09 7.11 16.28† 14.50† 14.76† 11.0214.61† 12.74† 16.56† 14.41† NA NA 19.88† 15.00†
Neutrophils (103/µL)
Day4 1.50 1.11 3.43† 3.84† 1.411.111.461.131.321.732.52†2.28† 2.002.52†
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Day10 NA NA NA NANANANANANANA8.796.55NANA
Day17 1.46 0.95 7.74† 6.52†5.35†4.14†5.89†5.54†7.98†6.96† NANA10.29† 7.37†
Monocytes (103/µL)
Day4 0.29 0.19 0.410.44† 0.300.230.260.180.210.200.410.37† 0.270.22
Day10 NA NA NA NANANANANANANA0.630.39NANA
Day17 0.31 0.19 0.570.370.63† 0.44† 0.62† 0.44† 0.550.40† NA NA 0.50 0.31
Eosinophils (103/µL)
Day4 0.121 0.134 0.121 0.1750.1190.1040.1240.1580.1190.1070.0970.1370.1100.162
Day10 NA NA NA NANANANANANANA0.0940.092 NANA
Day17 0.109 0.094 0.101 0.0990.1060.152*0.231†0.308†0.360†0.508† NANA0.566†0.573†
Basophils (103/µL)
Day4 0.026 0.026 0.0380.057†0.047* 0.0360.0350.0300.0420.0330.060†0.047†0.065†0.043*
Day10 NA NA NA NANANANANANANA0.1020.055 NANA
Day17 0.030 0.019 0.063† 0.060†0.069†0.039*0.060†0.042†0.063†0.043† NANA0.074†0.039*
Large unstained cells 
(103/µL)
Day4 0.09 0.09 0.66† 0.59†0.22†0.19† 0.150.110.22†0.31†0.41†0.33†0.35†0.37†
Day10 NA NA NA NANANANANANANA1.380.87NANA
Day17 0.09 0.08 1.17† 0.86†0.49†0.48†0.24†0.43†0.59†0.63† NANA0.69†0.54†
Fibrinogen (mg/dL)
Day10 NA NA NA NANANANANANANA298.2267.3 NANA
Day17 106.1 114.4 309.1† 314.0† 271.0† 279.8271.4† 281.8† 310.0† 299.1† NA NA 323.9† 297.8†
Clinical Chemistryi
Albumin (g/L)
Day4 29.48 31.61 26.70† 27.15†27.48†28.03†28.27†28.97†27.41†28.21†27.22†27.92†26.79†27.62†
Day10 NA NA NA NANANANANANANA27.3227.35 NANA
Day17 28.34 30.36 26.78† 27.68†26.67†27.69†27.23†27.38†27.26†27.17† NANA26.68†27.03†
Globulin (g/L)
Day4 27.12 27.69 29.70† 28.9527.6225.6731.43†30.33*29.59† 29.8928.88* 27.2829.11* 28.68
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Day10 NA NA NA NANANANANANANA28.0826.15 NANA
Day17 25.36 25.54 27.82† 29.02† 27.0328.5130.07†30.12†32.04†29.23† NANA31.22†30.07†
Albumin/Globulin Ratio
Day4 1.087 1.144 0.901† 0.938†0.996† 1.0950.902†0.958†0.929†0.950†0.944†1.028†0.923†0.964†
Day10 NA NA NA NANANANANANANA0.9751.049 NANA
Day17 1.119 1.192 0.963† 0.962†0.988† 1.0760.908†0.910†0.853†0.933† NANA0.856†0.901†
Gamma glutamyl
transferase (U/L)
Day4 0.95 0.88 4.21†3.67†2.93†2.75†2.52†2.323.32†3.72†3.60†3.77†3.25†4.01†
Day10 NA NA NA NANANANANANANA3.984.26NANA
Day17 1.621.214.43†3.97†3.04†3.32†3.59†3.94†4.18†4.40†NANA4.83†5.05†
Acute Phase Proteins 
1-Acid Glycoprotein
(µg/mL)
Day4 64.7 79.8465.0†401.4†304.7†323.6†381.9†378.9†454.9†445.0†431.1†390.6†446.8†445.6†
Day10 NA NA NA NANANANANANANA416.3409.7 NANA
Day17 50.3 52.0429.6† 467.7†737.0†649.4†437.6†463.0†970.9†980.9† NANA1043.6†826.1†
2-Macroglobulin 
(µg/mL)
Day4 39.8 18.1 727.0†126.2†223.0†57.1†1434.6†330.4†2143.1† 1639.4† 685.5†169.6†2159.0
†1362.6
†
Day 17 21.2 16.1 551.7† 269.3† 394.3† 102.5† 930.4† 724.0† 5927.3
†2692.2
†NA NA 4604.5
†1937.5
†
Urinalysis (Day 17) - - - -----------
Immunogenicity Neg Neg Pos PosPosPosPosPosPosPosPosPosPosPos
Cytokinesj- - - -----------
Organ Weightsd
Spleen
Absolute (g) 0.838 0.595 1.2 1.6 †1.3†1.2 1.1 1.31.2†1.6†1.2 1.3 1.3†1.6†
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Relative 
(g/1000g body weight)2.568 2.701 1.4†1.7†1.3†1.3 1.2 †1.2 1.3 †1.5†1.5 1.4 1.4 †1.6†
Gross Pathology
Number Examined 10 10 10 1010101010101010101010
Injection site
Induratedk0 0 10 10 7776661010 79
Incrusted 0 0 2 21000001100
Lymph node, iliac
Enlarged 0 0 1 14364781256
Spleen
Enlarged 0 0 2 45211575127
Histopathology (Day 17l)
Number Examined 10 10 10 1010101010101010101010
Injection siteb
Fibrosis intramuscular/
Interstitial
Minimal 0 0 1 00000110000
Mild 0 0 8101010 910 898101010
Moderate 0 0 0 00000001000
Fibrosis inter -
/perimuscular
Mild 0 0 10 101010 9101010 8101010
Moderate 0 0 0 00000001000
Inflammation, mixed,
subcutis 
(Injection site  1)
Mild 0 0 0 00010200000
Moderate 0 0 9101010 710 810 910 910
Marked 0 0 0 00020000010
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FDA-CBER-2021-5683-0708915
BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Inflammation, mixed,
intramuscular/
interstitial
(Injection site 1)
Minimal 0 0 1 0 0 0 0 0 1 0 0 0 0 0
Mild 0 0 4 8 8 4 1 4 3 8 4 3 4 9
Moderate 0 0 4 2 2 6 9 5 1 0 0 0 1 0
Inflammation, mixed,
intramuscular/interstitial,
multifocal  
(Injection site 1)
Moderate 0 0 0 0 0 0 0 1 4 2 5 7 5 1
Inflammation, mixed, 
inter-/perimuscular 
(Injection site1)
Minimal 0 0 0 0 0 0 0 0 1 0 0 0 0 0
Mild 0 0 3 0 0 0 1 0 0 0 0 0 0 0
Moderate 0 0 7 10 10 7 6 9 8 10 9 8 9 10
Marked 0 0 0 0 0 3 3 1 0 0 0 2 1 0
Inflammation, mixed,
subcutis 
(Injection site2)
Mild 0 0 0m0m0 0 0 0 1 1 0 0 0 2
Moderate 0 0 3m0m0 0 0 0 9 9 0 0 10 8
Inflammation, mixed,
intramuscular/interstitial
(Injection site2)
Mild 0 0 2m0m0 0 0 0 5 6 0 0 4 9
Moderate 0 0 1m0m0 0 0 0 0 0 0 0 0 0
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Inflammation, mixed,
intramuscular/interstitial,
multifocal 
(Injection site2)
Minimal 0 0 1m0m0000000000
Moderate 0 0 0m0m0000540061
Inflammation, mixed, 
inter-/perimuscular 
(Injection site2)
Minimal 0 0 1m0m0000000000
Moderate 0 0 2m0m00001010 001010
Myofiber degeneration
Minimal 0 0 2 00012120000
Mild 0 0 7 9998898741010
Moderate 0 0 0 00000001500
Edema, subcutis
Mild 0 0 1 01144120012
Moderate 0 0 510 9646786577
Marked 0 0 0 00210003521
Oedema intramuscular/
Interstitial
Minimal 0 0 1 86122111100
Mild 0 0 1 2176779891010
Oedema inter-/
perimuscular
Minimal 0 0 0 00100000000
Mild 0 0 2 15031022100
Moderate 0 0 4 95868866866
Marked 0 0 1 00111022145
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Hyperplasia, epidermis,
widespread
Mild 0 0 0 02357310021
Moderate 0 0 4 9744179910 79
Sciatic nerve, perineural
Inflammation
Minimal 0 0 0 00101310011
Mild 0 0 0 00003220023
Moderate 0 0 2 00010270055
Marked 0 0 1 00000000021
Bone femur
Inflammation
Minimal 0 0 0 10100120000
Mild 0 0 0 00000230027
Moderate 0 0 0 00000110002
Mammary gland
Inflammation , mixed;
interstitium; focal
Mild 0 0 0 00200102100
Moderate 0 0 0 00000101200
Lymph node iliac
Plasmacytosis
Minimal 0 0 2 21100104100
Mild 0 0 3 16621441692
Moderate 0 0 0 00077251018
Marked 0 0 0 00000100000
Inflammation
Minimal 0 0 4 10100021211
Mild 0 0 1 50200331375
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Moderate 0 0 0 00000222210
Increased cellularity,
germinal center
Minimal 4 3 3 10112100000
Mild 4 0 5 6679476810 86
Moderate 0 0 1 13202232024
Skeletal muscle
Infiltration, mixed
(focal,multifocal)
Minimal 0 0 0 10000120050
Spleen
Increased
haematopoiesis
Minimal 0 0 0 03200040026
Mild 0 0 0 00000230002
Liver
Vacuolation,
hepatocellular,
periportal
Minimal 0 0 1 41502511652
Mild 0 0 0 60108390448
Postdose Evaluation
Number Evaluated 5 5 5 55555555555
Body Temperature (C)
Day36 36.8 38.3 37.4 38.837.638.838.2*38.737.539.1 NANA37.039.2
Histopatholog yn
Number Examined 5 5 5 55555555555
Injection site
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FDA-CBER-2021-5683-0708919
BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
Dose (µgRNA/anim al) Control
(0)BNT162a1
(30)BNT162a1
(10)BNT162b1
(30)BNT162b1
(100)BNT162c1
(30)BNT162b2
(V8)
(100)
Dosing Frequency QWx3 QWx3 QWx3 QWx3 QWx3 QWx2 QWx3
Administration Sites/Dosing 
Day2 1 1 1 2 1 2
Sex M F M F M F M F M F M F M F
Fibrosis intramuscular/
interstitial
Minimal 0 0 1 33144410044
Fibrosis inter
/perimuscular
Minimal 0 0 1 11401251410
Mild 0 0 4 44154300044
Inflammation, inter -/
perimuscular
Minimal 0 0 3 24311321310
Mild 0 0 2 20044220044
Lymph node iliac
Plasmacytosis
Minimal 0 0 0 20223220111
Mild 0 0 0 10100130003
Increased cellularity,
germinal center
Minimal 1 2 3 21131104310
Mild 4 2 1 34314431143
Moderate 0 0 1 00110020001
Skeletal muscle
Infiltration,
lymphocyti c
Minimal 0 0 0 00000000001
Liver
Vacuolation,
hepatocellular,
periportal
Minimal 1 0 0 00000000100
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7A  Repeat-Dose Toxicity Study Number:  38166(continued)
p0.05; †p 0.01, significantly different from control based on appropriate trend or pairwise comparison.  A full description of the stat istical decision tree can 
be found in the final report for this study.
-= No note worthy findings; F = Female; GLP =Good Laboratory Practice; IFN = Interferon; I/H = Induration/Hardening; IL =Interleukin; LNP=Lipid
Nanoparticle; M = Male; modRNA =Nucleoside- modified mRNA; NA=Not applicable, Not available; Neg = Negative; Pos = Po sitive;QW=Once weekly;
RBD= Receptor binding domain; saRNA=Self-amplifying m RNA; SP2 =Spike protein P2 mutant ;TNF = Tum or necrosis factor; uRNA=Uridine mRNA .
a. Final, audited study report.
b. Groups1, 5, and 7 each received 100 µL/administration site at 2 sites for a total dose volume of 200 µL.  The remaining groups each received an 
administration at only 1 site for a total dose volume of 60 µL (Groups 2 and 4), 20 µL (Group 3), and 70 µL (Group 6).
c. Ten (10) animals/sex/group for the dosing phase (main study animals), and 5 animals/sex/group for the recovery phase.  Add itional satellite animals 
(3/sex/group) w ere used only for blood sampling for cytokine analysis.
d. Group means are shown for con trols.  Changes from controls, expressed as multiples, are shown for groups administered test article.  Statistical significa nce 
is based on actual data and not on the multiples.
e. Values represent data obtained from recovery animals (5/sex).
f. Percent d ifferences from Day 1 are shown.
g. For local tolerance, when animals received the test article over 2 injection sites (Groups 1, 5, and 7), only the highest severity score from either injection site 
was used to calculate incidence.
h. No notew orthy findings were observed at all time points on Day 1 (4, 24, 48, 96, and 144 hours postdose) and Day 15 (4 and 24 hours post dose).
i. Day 4 values represent data obtained from the first 5 main study animals/sex/group and all recovery animals (5/sex/group). Day 10 and 17 values represent 
data obtained at the end of the dosing phase from the main study animals only (10/sex/group).
j. Data obtained from all satellite animals (3/sex/group).  Cytokine parameters evaluated were IFN-, TNF-, IL-1-, IL-6, and IL-10.
k. Observation of “indurated” includes of observations of t hickened injection site and/or muscle.
l. Day10 for Group 6.
m. On Day15, 6animals (males 32, 34, 37, 39 and 42 ; female60) were administered their thirddose of BNT162a1 (Group2) in the contralateral limb (Site II) 
due to local tolerance findings at the original injection site (Site I).
n. Day31 for group 6 ; Day38 for all other groups.
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat -Dose ToxicityReport Title:  17 -Day Intramuscular Toxicity 
Study of BNT162b2 (V9) and
BNT162b3c i n Wistar Han Rats With 
a 3-Week RecoveryTest Article: BNT162b2
Species/Strain:  Rat/Wistar Han Duration of Dosing:  17Days(Dose days 1, 8, 15) Study Number:  20GR142
Age at First Dose:   9Weeks Duration of Postdose:  3Weeks Lot Numbers:   COVVAC/270320 
(BNT162b2 [V9]), BCV/040620 
(BNT162b3c)
Date of First Dose:   06July2020 Method of Adm inistration:  Intramuscular injection, QD, 
60µL/injectionaGLP Compliance:  Yes
Vehicle/Formulation:   0.9% sterile saline /Suspension
Special Features:  None
No Observed Adverse Effect Level:  NA
Dose (µgRNA) SalineControl
(0)BNT162b2 (V9)
(30)BNT162b3c
(30)
Sex M F M F M F
Number of Animalsb15 15 15 15 15 15
Noteworthy Findings
Died or Euthanized Moribund 0 0 0 0 0 0
Body Weight (g )c
Prior to Initiation of Dosing (Day6) 225.28 - - - 1.0 -
Day11 295.83 - - - 0.93† -
Day15 311.47 - - - 0.94* -
Body Weight Change(g)
Days1-4 -12.64 -11.61 -19.57† -14.21 -20.92† -15.75
Days 4-8 +28.44 +23.34 +36.01 +25.19 +33.75 +21.98
Days 8-11 +15.23 +3.71 +0.10† +1.37 -1.71† +3.92
Days 11-15 +15.64 +4.06 +18.82* +10.14† +18.71 +11.09†
Days 1-15 +46.67 +19.50 +35.35† +22.49 +29.83† +21.25
Food Consumptio n(g)c
Days 1-4 50.88 37.79 0.84† 0.87† 0.76† 0.92†
Days 4-8 90.87 74.46 1.06 0.95 1.01 0.96
Days8-11 64.77 48.27 0.83† 0.87† 0.78† 0.84†
Days 11-15 89.35 65.27 1.03 1.02 0.99 1.05
Days 1-15 295.87 225.80 0.97 0.94 0.91* 0.95
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat-Dose Toxicity Study Number:  20GR142 (continued)
Dose (µgRNA) SalineControl
(0)BNT162b2 (V9)
(30)BNT162b3c
(30)
Sex M F M F M F
Clinical Observations - - - - - -
Local Toleranc ed
Day1 –Edema
Predose - - - - - -
4Hours Postdose
Edema, very slight 0 0 0 0 0 1
24Hours Postdose
Edema, very slight 0 0 5 5 7 8
Edema, slight 0 0 6 10 6 7
48Hours Postdose
Edema, very slight NA NA 1 (6) 0 (10) 0 (6) 0 (7)
Edema, slight NA NA 5 (6) 10 (10) 6 (6) 7 (7)
72Hours Postdose
Edema, very slight NA NA 5 (6) 0 (10) 2 (6) 0 (7)
Edema, slight NA NA 0 (6) 10 (10) 4 (6) 7 (7)
120Hours Postdose
Edema, slight NA NA NA 10 (10) 4 (4) 7 (7)
144Hours Postdose
Edema, very slight NA NA NA 0 (10) 4 (4) 0 (7)
Edema, slight NA NA NA 10 (10) 0 (4) 7 (7)
Day8 –Edema
Predose - - - - - -
4Hours Postdose - - - - - -
24Hours Postdose
Edema, slight 0 0 6 6 4 6
Edema, moderate 0 0 7 9 11 9
48Hours Postdose
Edema, slight NA NA 6 (13) 6 3 4
Edema, moderate NA NA 7 (13) 9 12 11
72Hours Postdose
Edema, very slight NA NA 2 (13) 1 2 0
Edema, slight NA NA 11 (13) 8 13 8
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat-Dose Toxicity Study Number:  20GR142 (continued)
Dose (µgRNA) SalineControl
(0)BNT162b2 (V9)
(30)BNT162b3c
(30)
Sex M F M F M F
Edema, moderate NA NA 0 (13) 6 0 7
120Hours Postdose
Edema, very slight NA NA 11 (11) 14 (14) 13 (13) 8
Edema, slight NA NA 0 (11) 0 (14) 0 (13) 3
144Hours Postdose
Edema, very slight NA NA 1 (11) 0 (14) 0 (13) 1
Day15 –Edema
Predose - - - - - -
4Hours Postdose
Edema, very slight 0 0 2 0 5 0
24Hours Postdose
Edema, very slight 0 0 1 0 1 0
Edema, slight 0 0 11 6 11 4
Edema, moderate 0 0 2 9 3 11
48Hours Postdose
Edema, very slight NA NA 0 (13) 1 0 (14) 0
Edema, slight NA NA 11 (13) 8 10 (14) 6
Edema, moderate NA NA 2 (13) 6 4 (14) 9
72Hours Postdose
Edema, very slight NA NA 2 (4) 0 (5) 1 (5) 0 (5)
Edema, slight NA NA 2 (4) 3 (5) 4 (5) 2 (5)
Edema, moderate NA NA 0 (4) 2 (5) 0 (5) 3 (5)
Day1 –Erythem a
Predose - - - - - -
4Hours Postdose - - - - - -
24Hours Postdose
Erythema, very slight 0 0 1 11 1 15
48Hours Postdose
Erythema, very slight NA NA 0 (6) 10 (10) 1 (6) 7 (7)
72Hours Postdose
Erythema, very slight NA NA 0 (6) 9 (10) 0 (6) 7 (7)
120Hours Postdose
Erythema, very slight NA NA NA 9 (10) 0 (4) 7 (7)
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat-Dose Toxicity Study Number:  20GR142 (continued)
Dose (µgRNA) SalineControl
(0)BNT162b2 (V9)
(30)BNT162b3c
(30)
Sex M F M F M F
144Hours Postdose
Erythema, very slight NA NA NA 9 (10) 0 (4) 7 (7)
Day8 –Erythem a
Predose - - - - - -
4Hours Postdose - - - - - -
24Hours Postdose
Erythema, very slight 0 0 7 15 12 15
48Hours Postdose
Erythema, very slight NA NA 7 (13) 15 14 15
72Hours Postdose
Erythema, very slight NA NA 5 (13) 12 10 14
120Hours Postdose
Erythema, very slight NA NA 2 (11) 2 (14) 0 (13) 8
144Hours Postdose NA NA -(11) -(14) -(13) -
Day15 –Erythem a
Predose - - - - - -
4Hours Postdose
Erythema, very slight 0 0 0 0 1 0
24Hours Postdose
Erythema, very slight 0 0 0 12 0 15
48Hours Postdose
Erythema, very slight NA NA 0 (13) 3 3 (14) 12
72Hours Postdose
Erythema, very slight NA NA 0 (4) 2 (5) 0 (5) 4 (5)
Ophthalmology - - - - - -
Body temperature (C)e
Day1 38.31 38.08 38.85† 38.50* 39.02† 38.58†
Day8 37.07 37.81 38.05† 38.47† 38.33† 38.73†
Day15 37.34 38.02 38.37† 38.15 38.43† 38.35
Hematology/Coagulationf
RedBlood Cells (106/µL)
Day4 8.117 7.903 7.774* 7.381* 7.596† 7.470*
Day17 7.584 7.423 7.169 6.872† 7.113 6.836†
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat-Dose Toxicity Study Number:  20GR142 (continued)
Dose (µgRNA) SalineControl
(0)BNT162b2 (V9)
(30)BNT162b3c
(30)
Sex M F M F M F
Hemoglobin (g/dL)
Day4 15.01 14.53 14.16* 13.56* 14.01† 13.56*
Day17 13.82 13.83 12.53† 12.38† 12.81† 12.24†
Hematocrit (%)
Day4 48.04 44.91 43.37† 41.79* 43.79† 41.81*
Day17 42.61 41.67 38.40† 38.09† 39.29* 37.21†
Mean Cell Hemoglobin (pg)
Day4 18.51 18.37 18.20 18.39 18.50 18.16
Day17 18.27 18.62 17.48† 17.99† 18.01 17.89†
Mean Cell Hemoglobin Concentration (g/dL)
Day4 31.24 32.34 32.64† 32.49 32.04† 32.41
Day17 32.46 33.18 32.65 32.50† 32.61 32.84
Red Cell Distribution Width (%)
Day4 12.27 11.11 12.83 11.39 12.44 11.97†
Day17 11.63 11.33 14.12† 13.34† 13.73† 13.38†
Reticulocytes (103/µL)
Day4 392.1 301.7 107.4† 129.7† 104.6† 133.6†
Day17 178.8 168.9 185.4 222.1* 194.0 203.3
White Blood Cells (103/µL)
Day4 7.60 6.01 10.70* 7.84 9.70 8.57*
Day17 3.84 2.16 8.83† 5.70† 8.60† 6.37†
Neutrophils (103/µL)
Day4 1.083 0.920 2.470† 2.306 2.161* 2.879†
Day17 0.674 0.409 4.449† 2.469† 4.351† 2.879†
Monocytes (103/µL)
Day4 0.109 0.093 0.199* 0.176 0.214† 0.234†
Day17 0.071 0.056 0.234† 0.154† 0.254† 0.176†
Eosinophils (103/µL)
Day4 0.081 0.057 0.086 0.087* 0.091 0.123†
Day17 0.056 0.029 0.141† 0.092† 0.122† 0.097†
Basophils (103/µL)
Day4 0.016 0.009 0.030* 0.017 0.037† 0.024†
Day17 0.003 0.001 0.017† 0.008† 0.019† 0.010†
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat-Dose Toxicity Study Number:  20GR142 (continued)
Dose (µgRNA) SalineControl
(0)BNT162b2 (V9)
(30)BNT162b3c
(30)
Sex M F M F M F
Large Unstained Cells (103/µL)
Day4 0.046 0.030 0.187† 0.126† 0.183† 0.133†
Day17 0.026 0.010 0.209† 0.132† 0.323† 0.190†
Fibrinogen (mg/dL)
Day17 253.1 217.2 596.7† 541.9† 606.1† 563.1†
Clinical Chemistr yg
Albumin/Globulin Ratio
Day4 1.88 1.98 1.70† 1.71† 1.69† 1.69†
Day17 1.85 1.96 1.65† 1.61† 1.65† 1.66†
Total Protein (g/dL)
Day4 6.10 6.26 5.90 5.65† 5.85 5.94
Day17 5.39 5.44 5.51 4.98† 5.41 4.96†
Albumin (g/dL)
Day4 3.98 4.16 3.71† 3.56† 3.68† 3.73†
Day17 3.50 3.60 3.43 3.07† 3.38 3.09†
Globulin (g/dL)
Day4 2.13 2.10 2.19 2.09 2.18 2.21
Day17 1.89 1.84 2.08* 1.91 2.03 1.88
Acute Phase Proteinsg
2-Macroglobulin ( µg/mL)
Day4 113.4 212.1 2318.1† 703.8† 3911.6† 887.1†
Day17 14.0 33.1 990.6† 521.0† 1794.2† 592.0†
1-Acid Glycoprotein ( µg/mL)
Day4 174.358 239.774 1642.265 †1906.314 †2351.791 †1677.103 †
Day17 47.672 95.959 1835.986 †1491.849 †2021.083 †1651.071 †
Urinalysis (Day 17) - - - - - -
Immunogenicity Neg Neg Pos Pos Pos Pos
Organ Weights (Day 17)c
Spleen
Absolute (g) 0.5951 0.4382 1.29† 1.55† 1.34† 1.41†
Relative (g/100 g body weight) 0.2008 0.2202 1.42† 1.59† 1.52† 1.47†
Relative (g/g brain weight) 0.3120 0.2353 1.29† 1.62† 1.34† 1.43†
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat-Dose Toxicity Study Number:  20GR142 (continued)
Dose (µgRNA) SalineControl
(0)BNT162b2 (V9)
(30)BNT162b3c
(30)
Sex M F M F M F
Gross Pathology (Day 17)
Number Examined 10 10 10 10 10 10
Injection site
Abnormal color, p ale/dark 0 1 2 3 1 0
Abnormal consistency, f irm 0 0 2 4 2 7
Lymph node, draining
Abnormal size, enlarged 0 0 1 1 0 4
Spleen
Abnormal size, enlarged 0 0 0 0 0 1
Histopathology (Day 17)
Number Examinedh10 10 10 10 10 10
Injection site
Inflammation
Minimal 4 5 0 0 0 0
Mild 0 0 7 7 5 9
Moderate 0 0 3 3 5 1
Edema
Mild 0 0 8 9 8 9
Moderate 0 0 1 1 1 1
Lymph Node Iliac, Draining
Increased cellularity, Plasma cell
Minimal 0 0 1 (9) 1 4 1
Mild 0 0 4 (9) 1 3 5
Moderate 0 0 2 (9) 7 1 1
Increased cellularity, Germinal center
Minimal 1 1 2 (9) 3 2 4
Mild 1 1 4 (9) 2 6 2
Lymph Node, Inguinal
Increased cellularity, Plasma cell
Minimal 0 (9) 0 1 2 1 4
Increased cellularity, Germinal center
Minimal 0 (9) 1 1 3 1 6
Mild 1 (9) 0 4 3 5 3
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat-Dose Toxicity Study Number:  20GR142 (continued)
Dose (µgRNA) SalineControl
(0)BNT162b2 (V9)
(30)BNT162b3c
(30)
Sex M F M F M F
Liver
Vacuolation, Hepatocyte; Periportal
Minimal 0 0 5 10 7 7
Spleen
Increased cellularity, hematopoietic cell
Minimal 0 0 10 9 10 10
Increased cellularity, Germinal center
Minimal 0 0 5 6 5 5
Bone marrow , Sternum
Increased cellularity, hematopoietic cell
Minimal 0 0 10 10 10 10
Postdose Evaluation
Number of Animals 5 5 5 5 5 5
Body Weight (g)c
Day11 330.74 - 1.05 - 1.00 -
Day15 333.60 - 1.06 - 1.00 -
Day18 341.42 - 1.05 - 1.01 -
Day21 347.88 - 1.06 - 1.02 -
Food Consumption (g)c
Days 1-21 383.66 - 1.15 - 1.08 -
Hematology/Coagulation
Red Cell Distribution Width (%)
Day22 11.93 10.80 13.48† 13.04† 13.33 13.32†
Clinical Chemistry
Albumin/Globulin Ratio
Day22 1.76 1.90 1.72 1.72 1.70 1.80
Globulin (g/dL)
Day22 2.10 2.26 2.26† 2.40 2.18 2.42
Local Tolerance
Recovery Day 1 –Edema
72Hours Postdose
Edema, slight NA NA 2 3 4 2
Edema, moderate NA NA 0 2 0 3
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat-Dose Toxicity Study Number:  20GR142 (continued)
Dose (µgRNA) SalineControl
(0)BNT162b2 (V9)
(30)BNT162b3c
(30)
Sex M F M F M F
Immunogenicity Neg Neg Pos Pos Pos Pos
Gross Pathology (Day 22)
Number Examined 5 5 5 5 5 5
Lymph Node, Draining
Abnormal size, enlarged 0 0 1 0 0 1
Lymph Node, Inguinal
Abnormal size,enlarged 0 0 0 0 0 1
Histopathology (Day 22)
Number Examinedi5 5 5 5 5 5
Injection site
Inflammation
Minimal 0 0 5 5 5 5
Lymph Node, Draining
Increased cellularity, Plasma cell
Minimal 0 (4) 0 4 4 5 3
Increased cellularity, Germinal center
Minimal 0 (4) 1 3 2 2 4
Mild 0 (4) 0 1 1 2 1
Infiltration, Macrophage
Minimal 0 (4) 0 2 1 2 1
Mild 0 (4) 0 1 2 2 3
Lymph Node, Inguinal
Increased cellularity, Plasma cell
Minimal 0 0 0 0 0 1
Increased cellularity, Germinal center
Minimal 2 2 3 1 2 3
Infiltration, Macrophage
Minimal 0 0 0 0 1 1
Spleen
Increased cellularity, Germinal center
Minimal 0 0 1 2 1 2
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.7B  Repeat-Dose Toxicity Study Number:  20GR142 (continued)
p0.05; †p0.01, significantly different from control based on appropriate trend or pairwise comparison.  A full description of the statistical decision tree 
can be found in the final report for this study.
-=No notew orthy findings; F =Female; GLP =Good Laboratory Practice; M =Male; NA =Not applicable, results not yet available; Neg=Negative; 
Pos=Positive; QD =Once daily.
a. Each animal received a single intramuscular injection on each dose day.
b. Ten (10) animals/sex/group for the dosing phase (main study animals), and 5 animals/sex/group for the recovery phase.
c. Group means are shown for controls.  Changes from controls, expressed as multiples, are shown for groups administered test article.  Stat istical significance 
is based on actual data and not on the multiples.
d. Fifteen (15) animals/sex/group examined unless otherwise indicated in ( ).
e. Values represent the highest group mean postdose body temperature after each dose.
f. Day4 mean values for 7 animals/sex/group.; Day 17 mean values for 9 or 10 animals/sex/group.
g. Day4 mean values for 8 animals/sex/group.; Day 17 mean values for 9 to 10animals/sex/group.
h. Ten (10) animals/sex/group examined unless otherwise indicated in ( ).
i. Five (5) animals/sex/group examined unless otherwise indicated in ( ).
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.12 Reproductive and Developmental 
Toxicity –Fertility and DevelopmentReport Title: A Combined Fertility and 
Developmental Study (Including 
Teratogenicity and Postnatal 
Investigations) of BNT162b1, 
BNT162b2 and BNT162b3 by 
Intramuscular Administration in the 
Wistar RatTest Article : BNT162b2
Design Similar to ICH 4.1.1 , 4.1.2 and 4.1.3: Yes Duration of Dosing (F): 4Days (21 and 14 days 
prior to mating, GD 9, GD20)
Day of Mating (F): GD0Study Number: 20256434
Species/Strain:   Rat/Wistar Han
Age at First Dose (F):  11weeksSponsor Reference Number: 
RN9391R58
Date of First Dose:   27 July2020 Day of Cesarean Section:   GD 21
Day of Dam s and Pups Necropsy: PND21Lot Number s: CoVVAC/100320 
(BNT162b1), CoVVAC /270320 
(BNT162b2), BCV/040620 (BNT162b3)
Special Features:   None Method of Adm inistration:   Intramuscular injection, 
0.06mL/injectionGLP Compliance: Yes
No Observed Adverse Effect Level : Not reported Vehicle/Formulation:   0.9% sterile saline/Suspension
Control Article: Sterile physiological saline (0.9 % NaCl)
Dose (µgmRNA)aSaline Control
(0)BNT162b1
(30)BNT162b2
(30)BNT162b3
(30)
Dams
Number of Females
Caesarean Subgroup 22 22 22 22
Littering Subgroup 22 22 22 22
Clinical Observations
Injection site
Premating swellingb0 43 44 43
Gestation swellingb0 5 10 20
Lactation swellingb1 0 3 2
Premating Body Weight (g)c
Prior to Initiation of Dosing (Day 1) 216.49 1.00 1.01 1.02
Prior to Initiation of Mating (Day 22) 240.13 0.99 1.00 1.01
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.12  Reproductive and Developmental
Toxicity –Fertility and DevelopmentStudy Number:  20256434 (continued)
Dose (µgmRNA)aSaline Control
(0)BNT162b1
(30)BNT162b2
(30)BNT162b3
(30)
Premating Body Weight Change (g)
Days 1-4 4.85 -0.55§ -0.64§ -0.17§
Days 1-22 23.64 20.00 20.39 20.94
Gestation Body Weight (g)c
End of Gestation (GD 21) 365.98 0.98 0.96* 0.96*
Gestation Body Weight Change (g)
GD 9-12 13.55 7.48§ 5.70§ 5.73§
GD 18-21 34.10 29.33§ 24.82§ 29.24§
Lactation Body Weight - - - -
Premating Food Consumption (g)c
Days 1-8 18.49 0.90§ 0.91§ 0.91§
Days 1-22 18.43 0.97§ 0.98 0.98
Gestation Food Consumption (g)c
GD 9-12 22.95 0.87§ 0.84§ 0.83§
GD 18-21 23.41 0.98 0.97 0.99
Lactation Food Consumption - - - -
Number of Females Paired 44 44 44 44
Number of Females Failed to Mate 0 1 0 0
Number of Females Inseminated 44 43 44 44
Number of Pregnant Females 43 41 42 44
Number of Mistimed Pregnancy Females 0 0 0 1
Number of Not Pregnant Females 1 2 2 0
Number Euthanized Moribund Post -partum
(Littering subgroup)0 0 0 1d
Number Total Litter Death Post -partum
(Littering subgroup)0 1 0 1
Necropsy Observations (Macroscopic)
Injection site
Firm area 0 7 9 14
Enlarged 0 7 8 14
Oedematous area 0 0 1 0
Pale 0 2 4 10
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.12  Reproductive and Developmental
Toxicity –Fertility and DevelopmentStudy Number:  20256434 (continued)
Dose (µgmRNA)aSaline Control
(0)BNT162b1
(30)BNT162b2
(30)BNT162b3
(30)
Cesarean Subgroup
Cesarean Section Observations
Number Evaluated 21 20 21 22
Mean Number Corpora Lutea 14.7 15.3 15.5 15.0
Mean Number Implantations 14.1 14.6 14.0 13.8
Mean % Preimplantation Loss 4.09 4.77 9.77 7.96
Mean % Postimplantation Loss 6.10 3.36 5.85 8.64
Mean Number Early Resorptions 0.8 0.5 0.7 1.0
Mean Number Late Resorptions 0.1 0.0 0.2 0.2
Fetuses
Number Fetuses /Litters Evaluated 277/21 282/20 276/21 275/22
MeanNumber Live Fetuses 13.2 14.1 13.1 12.5
Mean Number Dead Fetuses 0 0 0 0
Mean Fetal Body Weight (both sex) (g) 4.89 4.86 4.90 4.84
Sex Ratios (% males) 46.96 48.09 50.66 49.84
Fetal Observations
External Malformations - - - -
External Variations /Abnormalities - - - -
Number Fetuses/Litters Evaluated 277/21 282/20 276/21 275/22
Visceral Malformations - - - -
Visceral Variations /Abnormalities - - - -
Number Fetuses/Litters Evaluated 133/21 135/20 132/21 132/22
Skeletal Malformations - - - -
SkeletalVariations /Abnormalities - - - -
Number Fetuses/Litters Evaluated 144/21 147/20 144/21 143/22
Littering Subgroup
Number with Mistimed Pregnancy 0 0 0 1
Number with Total Litter Death 0 1 0 1
No. of Natural Deliveries 22 21 21 20
Number Euthanized Moribund Post -Partum 0 0 0 1d
No. of Litters with Stillborn Pups 3 4 2 2
No. of litters with All Stillborn Pups 0 0 0 1
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BNT162b2
2.6.7 Toxicology Tabulated Summary
2.6.7.12  Reproductive and Developmental
Toxicity –Fertility and DevelopmentStudy Number:  20256434 (continued)
Dose (µgmRNA)aSaline Control
(0)BNT162b1
(30)BNT162b2
(30)BNT162b3
(30)
Mean No. Pups/Litter 13.3 11.9 13.1 11.4
Mean No. Liveborn Pups 13.0 11.0 13.0 11.3
No. of Total Litters Losses 0 1 0 1
Pre-Birth Loss (%) 6.80 12.22 8.22 13.76
No. of viable litters at Weaning (PND 21) 22 20 21 19
Gestation Index (%) 100 100 100 95
Live Birth Index (%) 98.0 93.2 99.3 94.7
Postnatal Survival to Day 4(%) 99.0 98.3 98.9 99.1
Postnatal Survival to Weaning (No. of pups) 175 154 163 152
Lactation Index(PND4-PND21) (%) 99.4 100.0 100.0 100.0
Sex ratio at Weaning (PND 21) (Males%) 49.7 50.6 47.6 49.3
Change in Pup Body Weight (g) - - - -
Pup Clinical Signs - - - -
Pup Necropsy Observations - - - -
Immunogenicity
Dams Neg Pos Pos Pos
Fetuses Neg Pos Pos Pos
Pups Neg Pos Pos Pos
*p<0.05, §p<0.001; Dunnett Non -Parametric2-Sided.  A full description of the statistical decision tree can be found in the final report for this study.
-=No notew orthy findings; F = f emale; GD = gestation day; GLP = Good Laboratory Practice; ICH = International Conference on Harmoni sation; 
mRNA=messenger RNA; Neg=negative; PND= postnatal day; Pos =positive.
a.Each dose consisted of a 0.06 mL intramuscular injection in alternating quadriceps muscles.
b. Complete recovery was noted betw een each of the dose administrations.  Swelling (associated or not with limping and/or piloerection for 1 or 2 days after the 
second dose only )was noted at the injection site.
c. Group means are shown for controls.  Changes from controls, expressed as multiples, are shown for groups administered test article.  Statistical significance 
is based on actual data and not on the multiples.
d.Difficulties during parturition.
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