COMIRNATY COVID-19 VACCIN 30mcg / dose injection dispersion medication leaflet

Comirnaty Omicron XBB.1.5 10 micrograms/dose concentrate for dispersion for injection

Comirnaty Omicron XBB.1.5 3 micrograms/dose concentrate for dispersion for injection

COVID−19 mRNA Vaccine

Table 1. Comirnaty Omicron XBB.1.5 qualitative and quantitative composition

Doses percontainer

Product (see sectionspresentation Container 4.2 and 6.6) Content per dose

Comirnaty

Omicron XBB.1.510 micrograms/do Multidose vial 10 doses of One dose (0.2 mL) contains 10 microgramsse concentrate for (1.3 mL) 0.2 mL after of raxtozinameran, a COVID−19 mRNA

Vaccine (nucleoside modified, embedded indispersion for (orange cap) dilution lipid nanoparticles).injection

Multidose vial 10 doses of One dose (0.2 mL) contains 3 micrograms of

Comirnaty (0.4 mL) 0.2 mL after raxtozinameran, a COVID−19 mRNA

Omicron XBB.1.5 (maroon cap) dilution Vaccine (nucleoside modified, embedded in3 micrograms/dos lipid nanoparticles).e concentrate fordispersion for Multidose vial 3 doses of One dose (0.3 mL) contains 3 micrograms ofinjection (0.48 mL) 0.3 mL after raxtozinameran, a COVID−19 mRNA(yellow cap) dilution Vaccine (nucleoside modified, embedded inlipid nanoparticles).

Raxtozinameran is a single-stranded, 5’-capped messenger RNA (mRNA) produced using a cell-freein vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of

SARS-CoV-2 (Omicron XBB.1.5).

For the full list of excipients, see section 6.1.

Concentrate for dispersion for injection (sterile concentrate).

Comirnaty Omicron XBB.1.5 10 micrograms/dose concentrate for dispersion for injection is a white tooff-white dispersion (pH: 6.9 - 7.9).

Comirnaty Omicron XBB.1.5 3 micrograms/dose concentrate for dispersion for injection:

Container Appearance

Multidose vial (0.4 mL) The vaccine is a white to off-white dispersion (pH: 6.9 - 7.9).(maroon cap)

Multidose vial (0.48 mL) The vaccine is a clear to slightly opalescent dispersion(yellow cap) (pH: 6.9 - 7.9).

Comirnaty Omicron XBB.1.5 concentrate for dispersion for injection is indicated for activeimmunisation to prevent COVID-19 caused by SARS-CoV-2 in infants and children aged 6 months to11 years.

The use of this vaccine should be in accordance with official recommendations.

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age)

Comirnaty Omicron XBB.1.5 10 micrograms/dose concentrate for dispersion for injection isadministered intramuscularly after dilution as a single dose of 0.2 mL for children 5 to 11 years of ageregardless of prior COVID-19 vaccination status (see sections 4.4 and 5.1).

For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty Omicron

XBB.1.5 should be administered at least 3 months after the most recent dose of a COVID-19 vaccine.

Infants and children 6 months to 4 years of age without history of completion of a COVID-19 primarycourse or prior SARS-CoV-2 infection

Comirnaty Omicron XBB.1.5 3 micrograms/dose concentrate for dispersion for injection isadministered intramuscularly after dilution as a primary course of 3 doses. It is recommended toadminister the second dose 3 weeks after the first dose followed by a third dose administered at least 8weeks after the second dose (see sections 4.4 and 5.1).

If a child turns 5 years old between their doses in the primary course, he/she should complete theprimary course at the same 3 micrograms dose level.

Infants and children 6 months to 4 years of age with history of completion of a COVID-19 primarycourse or prior SARS-CoV-2 infection

Comirnaty Omicron XBB.1.5 3 micrograms/dose concentrate for dispersion for injection isadministered intramuscularly after dilution as a single dose for infants and children 6 months to4 years of age.

For individuals who have previously been vaccinated with a COVID-19 vaccine, Comirnaty Omicron

XBB.1.5 should be administered at least 3 months after the most recent dose of a COVID-19 vaccine.

Severely immunocompromised individuals

Additional doses may be administered to individuals who are severely immunocompromised inaccordance with national recommendations (see section 4.4).

The Comirnaty Omicron XBB.1.5 3 micrograms/dose primary course may consist of any previous orcurrent Comirnaty vaccine but not exceeding the total number of doses required as primary course.

The primary course should only be administered once.

The interchangeability of Comirnaty with COVID-19 vaccines from other manufacturers has not beenestablished.

The safety and efficacy of the vaccine in infants aged less than 6 months have not yet beenestablished.

Comirnaty Omicron XBB.1.5 concentrate for dispersion for injection should be administeredintramuscularly after dilution (see section 6.6).

Orange cap (10-dose vial) or maroon cap (10-dose vial)

After dilution, vials with an orange cap or maroon cap of Comirnaty Omicron XBB.1.5 contain10 doses of 0.2 mL of vaccine. In order to extract 10 doses from a single vial, low dead-volumesyringes and/or needles should be used. The low dead-volume syringe and needle combination shouldhave a dead-volume of no more than 35 microlitres. If standard syringes and needles are used, theremay not be sufficient volume to extract 10 doses from a single vial. Irrespective of the type of syringeand needle:

* Each dose must contain 0.2 mL of vaccine.

* If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard thevial and any excess volume.

* Do not pool excess vaccine from multiple vials.

Yellow cap (3-dose vial)

After dilution, vials with a yellow cap of Comirnaty Omicron XBB.1.5 contain 3 doses of 0.3 mL ofvaccine. Standard syringes and needles can be used to extract 3 doses from a single vial. Irrespectiveof the type of syringe and needle:

* Each dose must contain 0.3 mL of vaccine.

* If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard thevial and any excess volume.

* Do not pool excess vaccine from multiple vials.

In infants from 6 to less than 12 months of age, the recommended injection site is the anterolateralaspect of the thigh. In individuals 1 to 4 years of age, the recommended injection site is theanterolateral aspect of the thigh or the deltoid muscle. In individuals 5 years of age and older thepreferred site is the deltoid muscle of the upper arm.

Do not inject the vaccine intravascularly, subcutaneously or intradermally.

The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products.

For precautions to be taken before administering the vaccine, see section 4.4.

For instructions regarding thawing, handling and disposal of the vaccine, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.

Events of anaphylaxis have been reported. Appropriate medical treatment and supervision shouldalways be readily available in case of an anaphylactic reaction following the administration of thevaccine.

Close observation for at least 15 minutes is recommended following vaccination. No further dose ofthe vaccine should be given to those who have experienced anaphylaxis after a prior dose of

Comirnaty.

There is an increased risk of myocarditis and pericarditis following vaccination with Comirnaty. Theseconditions can develop within just a few days after vaccination and have primarily occurred within14 days. They have been observed more often after the second vaccination, and more often in youngermales (see section 4.8). Available data indicate that most cases recover. Some cases required intensivecare support and fatal cases have been observed.

Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis.

Vaccinees (including parents or caregivers) should be instructed to seek immediate medical attentionif they develop symptoms indicative of myocarditis or pericarditis such as (acute and persisting) chestpain, shortness of breath, or palpitations following vaccination.

Healthcare professionals should consult guidance and/or specialists to diagnose and treat thiscondition.

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐relatedreactions (e.g. dizziness, palpitations, increases in heart rate, alterations in blood pressure,paraesthesia, hypoaesthesia and sweating) may occur in association with the vaccination process itself.

Stress-related reactions are temporary and resolve on their own. Individuals should be advised to bringsymptoms to the attention of the vaccination provider for evaluation. It is important that precautionsare in place to avoid injury from fainting.

Vaccination should be postponed in individuals suffering from acute severe febrile illness or acuteinfection. The presence of a minor infection and/or low-grade fever should not delay vaccination.

As with other intramuscular injections, the vaccine should be given with caution in individualsreceiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such ashaemophilia) because bleeding or bruising may occur following an intramuscular administration inthese individuals.

Safety and immunogenicity have been assessed in a limited number of immunocompromisedindividuals, including those receiving immunosuppressant therapy (see sections 4.8 and 5.1). Theefficacy of Comirnaty Omicron XBB.1.5 may be lower in immunocompromised individuals.

The duration of protection afforded by the vaccine is unknown as it is still being determined byongoing clinical trials.

As with any vaccine, vaccination with Comirnaty Omicron XBB.1.5 may not protect all vaccinerecipients. Individuals may not be fully protected until 7 days after their vaccination.

No interaction studies have been performed.

Concomitant administration of Comirnaty Omicron XBB.1.5 with other vaccines has not been studied.

No data are available yet regarding the use of Comirnaty Omicron XBB.1.5 during pregnancy.

However, there are limited clinical study data (less than 300 pregnancy outcomes) from the use of

Comirnaty in pregnant participants. A large amount of observational data from pregnant womenvaccinated with the initially approved Comirnaty vaccine during the second and third trimester havenot shown an increase in adverse pregnancy outcomes. While data on pregnancy outcomes followingvaccination during the first trimester are presently limited, no increased risk for miscarriage has beenseen. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy,embryo/foetal development, parturition or post-natal development (see section 5.3). Based on dataavailable with other vaccine variants, Comirnaty Omicron XBB.1.5 can be used during pregnancy.

No data are available yet regarding the use of Comirnaty Omicron XBB.1.5 during breast-feeding.

However, no effects on the breastfed newborn/infant are anticipated since the systemic exposure ofbreast-feeding woman to the vaccine is negligible. Observational data from women who werebreast-feeding after vaccination with the initially approved Comirnaty vaccine have not shown a riskfor adverse effects in breastfed newborns/infants. Comirnaty Omicron XBB.1.5 can be used duringbreast-feeding.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity(see section 5.3).

Comirnaty Omicron XBB.1.5 has no or negligible influence on the ability to drive, cycle, and usemachines. However, some of the effects mentioned under section 4.8 may temporarily affect theability to drive, cycle, or use machines.

The safety of Comirnaty Omicron XBB.1.5 is inferred from safety data of the prior Comirnatyvaccines.

Initially approved Comirnaty vaccine

Infants 6 to 23 months of age - after 3 doses

In an analysis of Study 3 (Phase 2/3), 2 176 infants (1 458 initially approved Comirnaty 3 mcg and718 placebo) were 6 to 23 months of age. Based on data in the blinded placebo-controlled follow-upperiod up to the cut-off date of 28 February 2023, 720 infants 6 to 23 months of age who received a3-dose primary course (483 Comirnaty 3 mcg and 237 placebo) have been followed for a median of1.7 months after the third dose.

The most frequent adverse reactions in infants 6 to 23 months of age that received any primary coursedose included irritability (> 60%), drowsiness (> 40%), decreased appetite (> 30%), tenderness at theinjection site (> 20%), injection site redness and fever (> 10%).

Children 2 to 4 years of age - after 3 doses

In an analysis of Study 3 (Phase 2/3), 3 541 children (2 368 Comirnaty 3 mcg and 1 173 placebo) were2 to 4 years of age. Based on data in the blinded placebo-controlled follow-up period up to the cut-offdate of 28 February 2023, 1 268 children 2 to 4 years of age who received a 3-dose primary course(863 Comirnaty 3 mcg and 405 placebo) have been followed a median of 2.2 months after the thirddose.

The most frequent adverse reactions in children 2 to 4 years of age that received any primary coursedose included pain at injection site and fatigue (> 40%), injection site redness and fever (> 10%).

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after 2 doses

In Study 3, a total of 3 109 children 5 to 11 years of age received at least 1 dose of the initiallyapproved Comirnaty vaccine and a total of 1 538 children 5 to 11 years of age received placebo. At thetime of the analysis of Study 3 Phase 2/3 with data up to the cut-off date of 20 May 2022,2 206 (1 481 Comirnaty 10 mcg and 725 placebo) children have been followed for ≥ 4 months afterthe second dose in the placebo-controlled blinded follow-up period. The safety evaluation in Study 3 isongoing.

The overall safety profile of Comirnaty in participants 5 to 11 years of age was similar to that seen inparticipants 16 years of age and older. The most frequent adverse reactions in children 5 to 11 years ofage that received 2 doses were injection site pain (> 80%), fatigue (> 50%), headache (> 30%),injection site redness and swelling (≥ 20%), myalgia, chills and diarrhoea (> 10%).

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after booster dose

In a subset from Study 3, a total of 2 408 children 5 to 11 years of age received a booster dose of

Comirnaty 10 mcg at least 5 months (range of 5.3 to 19.4 months) after completing the primary series.

The analysis of the Study 3 Phase 2/3 subset is based on data up to the cut-off date of28 February 2023 (median follow-up time of 6.4 months).

The overall safety profile for the booster dose was similar to that seen after the primary course. Themost frequent adverse reactions in children 5 to 11 years of age after the booster dose were injectionsite pain (> 60%), fatigue (> 30%), headache (> 20%), myalgia, chills, injection site redness andswelling (> 10%).

In an analysis of long-term safety follow-up in Study 2, 2 260 adolescents (1 131 Comirnaty and1 129 placebo) were 12 to 15 years of age. Of these, 1 559 adolescents (786 Comirnaty and773 placebo) have been followed for ≥ 4 months after the second dose.

The overall safety profile of Comirnaty in adolescents 12 to 15 years of age was similar to that seen inparticipants 16 years of age and older. The most frequent adverse reactions in adolescents 12 to15 years of age that received 2 doses were injection site pain (> 90%), fatigue and headache (> 70%),myalgia and chills (> 40%), arthralgia and pyrexia (> 20%).

In Study 2, a total of 22 026 participants 16 years of age or older received at least 1 dose of Comirnaty30 mcg and a total of 22 021 participants 16 years of age or older received placebo (including 138 and145 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively). A total of20 519 participants 16 years of age or older received 2 doses of Comirnaty.

At the time of the analysis of Study 2 with a data cut-off of 13 March 2021 for the placebo-controlledblinded follow-up period up to the participants’ unblinding dates, a total of 25 651 (58.2%)participants (13 031 Comirnaty and 12 620 placebo) 16 years of age and older were followed up for≥ 4 months after the second dose. This included a total of 15 111 (7 704 Comirnaty and 7 407 placebo)participants 16 to 55 years of age and a total of 10 540 (5 327 Comirnaty and 5 213 placebo)participants 56 years of age and older.

The most frequent adverse reactions in participants 16 years of age and older that received 2 doseswere injection site pain (> 80%), fatigue (> 60%), headache (> 50%), myalgia (> 40%), chills(> 30%), arthralgia (> 20%), pyrexia and injection site swelling (> 10%) and were usually mild ormoderate in intensity and resolved within a few days after vaccination. A slightly lower frequency ofreactogenicity events was associated with greater age.

The safety profile in 545 participants 16 years of age and older receiving Comirnaty, that wereseropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.

Participants 12 years of age and older - after booster dose

A subset from Study 2 Phase 2/3 participants of 306 adults 18 to 55 years of age who completed theoriginal Comirnaty 2-dose course, received a booster dose of Comirnaty approximately 6 months(range of 4.8 to 8.0 months) after receiving Dose 2. Overall, participants who received a booster dose,had a median follow-up time of 8.3 months (range 1.1 to 8.5 months) and 301 participants had beenfollowed for ≥ 6 months after the booster dose to the cut-off date (22 November 2021).

The overall safety profile for the booster dose was similar to that seen after 2 doses. The most frequentadverse reactions in participants 18 to 55 years of age were injection site pain (> 80%),fatigue (> 60%), headache (> 40%), myalgia (> 30%), chills and arthralgia (> 20%).

In Study 4, a placebo-controlled booster study, participants 16 years of age and older recruited from

Study 2 received a booster dose of Comirnaty (5 081 participants), or placebo (5 044 participants) atleast 6 months after the second dose of Comirnaty. Overall, participants who received a booster dose,had a median follow-up time of 2.8 months (range 0.3 to 7.5 months) after the booster dose in theblinded placebo-controlled follow-up period to the cut-off date (8 February 2022). Of these,1 281 participants (895 Comirnaty and 386 placebo) have been followed for ≥ 4 months after thebooster dose of Comirnaty. No new adverse reactions of Comirnaty were identified.

A subset from Study 2 Phase 2/3 participants of 825 adolescents 12 to 15 years of age who completedthe original Comirnaty 2-dose course, received a booster dose of Comirnaty approximately11.2 months (range of 6.3 to 20.1 months) after receiving Dose 2. Overall, participants who received abooster dose, had a median follow-up time of 9.5 months (range 1.5 to 10.7 months) based on data upto the cut-off date (3 November 2022). No new adverse reactions of Comirnaty were identified.

Booster dose following primary vaccination with another authorised COVID-19 vaccine

In 5 independent studies on the use of a Comirnaty booster dose in individuals who had completedprimary vaccination with another authorised COVID-19 vaccine (heterologous booster dose), no newsafety issues were identified.

Omicron-adapted Comirnaty

Infants 6 to 23 months of age - after the booster (fourth dose)

In 2 groups from Study 6 (Phase 3, Groups 2 and 3), 160 participants (Group 2: 92, Group 3: 68) 6 to23 months of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of

Comirnaty Original/Omicron BA.4-5 (1.5/1.5 mcg) 2.1 to 8.6 months after receiving Dose 3 for Group2 and 3.8 to 12.5 months after receiving Dose 3 for Group 3. Participants who received a booster(fourth dose) of Comirnaty Original/Omicron BA.4-5 had a median follow-up time of 4.4 months for

Group 2 and had a median follow-up time of 6.4 months for Group 3.

The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) wassimilar to that seen after 3 doses. The most frequent adverse reaction in participants 6 to 23 months ofage was irritability (> 30%), decreased appetite (> 20%), drowsiness, tenderness at the injection siteand fever (> 10%).

Children 2 to 4 years of age - after the booster (fourth dose)

In 2 groups from Study 6 (Phase 3, Groups 2 and 3), 1 207 participants (Group 2: 218, Group 3: 989) 2to 4 years of age who had completed 3 doses of Comirnaty, received a booster (fourth dose) of

Comirnaty Original/Omicron BA.4-5 (1.5/1.5 mcg) 2.1 to 8.6 months after receiving Dose 3 for Group2 and 2.8 to 17.5 months after receiving Dose 3 for Group 3. Participants who received a booster(fourth dose) of Comirnaty Original/Omicron BA.4-5 had a median follow-up time of 4.6 months for

Group 2 and had a median follow-up time of 6.3 months for Group 3.

The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) wassimilar to that seen after 3 doses. The most frequent adverse reactions in participants 2 to 4 years ofage were injection site pain (> 30%) and fatigue (> 20%).

Children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after the booster (fourth dose)

In a subset from Study 6 (Phase 3), 113 participants 5 to 11 years of age who had completed 3 doses of

Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (5/5 mcg) 2.6 to8.5 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5 had a median follow-up time of 6.3 months.

The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) wassimilar to that seen after 3 doses. The most frequent adverse reactions in participants 5 to 11 years ofage were injection site pain (> 60%), fatigue (> 40%), headache (> 20%), and muscle pain (> 10%).

Participants 12 years of age and older - after a booster dose of Comirnaty Original/Omicron BA.4-5(fourth dose)

In a subset from Study 5 (Phase 2/3), 107 participants 12 to 17 years of age, 313 participants 18 to55 years of age and 306 participants 56 years of age and older who had completed 3 doses of

Comirnaty, received a booster (fourth dose) of Comirnaty Original/Omicron BA.4-5 (15/15 mcg) 5.4to 16.9 months after receiving Dose 3. Participants who received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5 had a median follow-up time of at least 1.5 months.

The overall safety profile for the Comirnaty Original/Omicron BA.4-5 booster (fourth dose) wassimilar to that seen after 3 doses. The most frequent adverse reactions in participants 12 years of ageand older were injection site pain (> 60%), fatigue (> 50%), headache (> 40%), muscle pain (> 20%),chills (> 10%), and joint pain (> 10%).

Tabulated list of adverse reactions from clinical studies of Comirnaty and Comirnaty

Original/Omicron BA.4-5 and post-authorisation experience of Comirnaty in individuals 6 months ofage and older

Adverse reactions observed during clinical studies and post-authorisation experience are listed belowaccording to the following frequency categories: Very common (≥ 1/10), Common (≥ 1/100 to< 1/10), Uncommon (≥ 1/1 000 to < 1/100), Rare (≥ 1/10 000 to < 1/1 000), Very rare (< 1/10 000),

Not known (cannot be estimated from the available data).

Table 2. Adverse reactions from Comirnaty and Comirnaty Original/Omicron BA.4-5 clinicaltrials and Comirnaty post-authorisation experience in individuals 6 months of ageand older

System Organ Class Frequency Adverse reactions

Blood and lymphatic system Common Lymphadenopathyadisorders

Immune system disorders Uncommon Hypersensitivity reactions (e.g. rashi,pruritus, urticariab, angioedemab)

Not known Anaphylaxis

Metabolism and nutrition disorders Uncommon Decreased appetitej

Psychiatric disorders Very common Irritabilityk

Uncommon Insomnia

Nervous system disorders Very common Headache; drowsinessk

Uncommon Dizzinessd; lethargy

Rare Acute peripheral facial paralysisc

Not known Paraesthesiad; hypoaesthesiad

Cardiac disorders Very rare Myocarditisd; pericarditisd

System Organ Class Frequency Adverse reactions

Gastrointestinal disorders Very common Diarrhoead

Common Nausea; vomitingd,m

Skin and subcutaneous tissue Uncommon Hyperhidrosis; night sweatsdisorder Not known Erythema multiformed

Musculoskeletal and connective Very common Arthralgia; myalgiatissue disorders Uncommon Pain in extremitye

Reproductive system and breast Not known Heavy menstrual bleedingldisorders

General disorders and Very common Injection site pain; injection siteadministration site conditions tendernessk; fatigue; chills; pyrexiaf;injection site swelling

Common Injection site rednessh

Uncommon Asthenia; malaise; injection site pruritus

Not known Extensive swelling of vaccinated limbd;facial swellingg

a. In participants 5 years of age and older, a higher frequency of lymphadenopathy was reported after abooster (≤ 2.8%) dose than after primary (≤ 0.9%) doses of the vaccine.

b. The frequency category for urticaria (participants 5 years and older) and angioedema (participants 6 monthsand older) was rare.

c. Through the clinical trial safety follow-up period to 14 November 2020, acute peripheral facial paralysis (orpalsy) was reported by four participants in the COVID-19 mRNA Vaccine group. Onset was Day 37 after

Dose 1 (participant did not receive Dose 2) and Days 3, 9, and 48 after Dose 2. No cases of acute peripheralfacial paralysis (or palsy) were reported in the placebo group.

d. Adverse reaction determined post-authorisation.

e. Refers to vaccinated arm.

f. A higher frequency of pyrexia was observed after the second dose compared to the first dose.g. Facial swelling in vaccine recipients with a history of injection of dermatological fillers has been reported inthe post-marketing phase.h. Injection site redness occurred at a higher frequency (very common) in participants 6 months to 11 years ofage and in immunocompromised participants 2 years of age and older.i. The frequency category for rash was common in participants 6 to 23 months of age.j. The frequency category for decreased appetite was very common in participants 6 to 23 months of age.k. Irritability, injection site tenderness, and drowsiness pertain to participants 6 to 23 months of age.l. Most cases appeared to be non-serious and temporary in nature.m. The frequency category for vomiting was very common in pregnant women 18 years of age and older and inimmunocompromised participants 2 to 18 years of age.

Infants born to pregnant participants - after 2 doses of Comirnaty

Study C4591015 (Study 9), a Phase 2/3, placebo-controlled study, evaluated a total of 346 pregnantparticipants who received Comirnaty (n = 173) or placebo (n = 173). Infants (Comirnaty n = 167 orplacebo n = 168) were evaluated up to 6 months. No safety concerns were identified that wereattributable to maternal vaccination with Comirnaty.

Immunocompromised participants (adults and children)

In study C4591024 (Study 10), a total of 124 immunocompromised participants 2 years of age andolder received Comirnaty (see section 5.1).

The increased risk of myocarditis after vaccination with Comirnaty is highest in younger males (seesection 4.4).

Two large European pharmacoepidemiological studies have estimated the excess risk in youngermales following the second dose of Comirnaty. One study showed that in a period of 7 days after thesecond dose there were about 0.265 (95% CI: 0.255 - 0.275) extra cases of myocarditis in 12-29 yearold males per 10 000 compared to unexposed persons. In another study, in a period of 28 days after thesecond dose there were 0.56 (95% CI: 0.37 - 0.74) extra cases of myocarditis in 16-24 year old malesper 10 000 compared to unexposed persons.

Limited data indicate that the risk of myocarditis and pericarditis after vaccination with Comirnaty inchildren aged 5 to 11 years seems lower than in ages 12 to 17 years.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

There have been reports of higher than recommended doses of Comirnaty in clinical trials andpost−authorisation experience. In general, adverse events reported with overdoses have been similar tothe known adverse reaction profile of Comirnaty.

In the event of overdose, monitoring of vital functions and possible symptomatic treatment isrecommended.

Pharmacotherapeutic group: vaccines, viral vaccines, ATC code: J07BN01

The nucleoside modified messenger RNA in Comirnaty is formulated in lipid nanoparticles, whichenable delivery of the non-replicating RNA into host cells to direct transient expression of the

SARS-CoV-2 S antigen. The mRNA codes for membrane-anchored, full-length S with two pointmutations within the central helix. Mutation of these two amino acids to proline locks S in anantigenically preferred prefusion conformation. The vaccine elicits both neutralising antibody andcellular immune responses to the spike (S) antigen, which may contribute to protection against

COVID-19.

Omicron-adapted Comirnaty

Immunogenicity in infants and children 6 months to 4 years of age - after the booster (fourth dose)

In an analysis of a subset from Study 6, 310 participants 6 months to 4 years of age received a booster(fourth dose) of Comirnaty Original/Omicron BA.4-5 (1.5/1.5 mcg) after receiving 3 prior doses of

Comirnaty 3 micrograms dose concentrate for dispersion. Results include immunogenicity data from acomparator subset of participants 6 months to 4 years of age in Study 3 who received 3 doses of

Comirnaty 3 micrograms dose concentrate for dispersion.

Analyses of NT50 against Omicron BA.4-5 and against reference strain among participants 6 monthsto 5 years of age who received Comirnaty (Bivalent BA.4-5) as a booster dose in Study 6 compared toa subset of participants from Study 3 who received 3 doses of Comirnaty demonstrated superiority ofanti-Omicron BA.4-5 response based on GMR and noninferiority based on difference in seroresponserates, and noninferiority of anti-reference strain immune response based on GMR and difference inseroresponse rates (Table 3).

Table 3. Substudy B group 2 - Geometric mean ratios and difference in percentages ofparticipants with seroresponse (1 month after dose 4 study 6/1 month after dose 3study 3) - participants with or without evidence of infection - 6 months to 4 years ofage - evaluable immunogenicity population

Geometric mean ratios (1 month after dose 4 study 6/1 month after dose 3 study 3)

Comirnaty(Bivalent

BA.4-5)

Comirnaty (Bivalent BA.4-5) (3 mcg) /(3 mcg) Comirnaty (3 mcg) Comirnaty

Study 6 Subset of Study 3 (3 mcg)

GMTb GMTb GMRc

Assayf na (95% CIb) na (95% CIb) (95% CI)c

SARS-CoV-2neutralisation assay -

Omicron BA.4-5 - NT50 1 839.3 941.0 1.95(titre) 223 (1 630.5, 2 074.9) 238 (838.1,1 058.2) (1.65, 2.31)d

SARS-CoV-2neutralisation assay -reference strain - NT50 6 636.3 7 305.4 0.91(titre) 223 (6 017.5, 7 318.8) 238 (6 645.5, 8 030.7) (0.79, 1.04)e

Difference in percentages of participants with seroresponse (1 month after dose 4 study 6/1month after dose 3 study 3)

Assayf Comirnaty (Bivalent BA.4-5) Comirnaty (3 mcg) Difference(3 mcg) Subset of Study 3

Study 6

Ng nh (%) Ng nh (%) %j(95% CIi) (95% CIi) (95% CIk)

SARS-CoV-2 223 149 (66.8) 238 120 (50.4) 19.99neutralisation assay - (60.2, 73.0) (43.9, 56.9) (11.61, 28.36)l

Omicron BA.4-5 - NT50(titre)

SARS-CoV-2 223 110 (49.3) 238 141 (59.2) -0.15neutralisation assay - (42.6, 56.1) (52.7, 65.5) (-7.79, 7.48)mreference strain - NT50(titre)

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre; LLOQ =lower limit of quantitation; LSMeans = least square means; NT50 = 50% neutralising titre; SARS-CoV-2 =severe acute respiratory syndrome coronavirus 2.

Note: Seroresponse is defined as achieving a ≥ 4-fold rise from baseline (before the first dose of studyvaccination). If the baseline measurement is below the LLOQ, the post-vaccination measure of ≥ 4 × LLOQ isconsidered seroresponse.

a. n = Number of participants with valid and determinate assay results for the specified assay at the givensampling time point.

b. GMTs and 2-sided CIs were calculated by exponentiating the LSMeans and the corresponding CIs based onanalysis of log-transformed assay results using a linear regression model with baseline log-transformedneutralising titres, postbaseline infection status, age group (for ≥ 6 Months to < 5 Years only) and vaccinegroup as covariates. Assay results below the LLOQ were set to 0.5 × LLOQ.

c. GMRs and 2-sided CIs were calculated by exponentiating the difference of LSMeans for the assay and thecorresponding CIs based on the same regression model as stated above.

d. Superiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 1.

e. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 0.67 and thepoint estimate of the GMR is ≥ 0.8.

f. SARS-CoV-2 NT50 were determined using a validated 384-well assay platform (original strain [USA-

WA1/2020, isolated in January 2020] and Omicron B.1.1.529 subvariant BA.4/BA.5).g. N = Number of participants with valid and determinate assay results for the specified assay at both thepre-vaccination time point and the given sampling time point. These values are the denominators for thepercentage calculations.

h. n = Number of participants with seroresponse for the given assay at the given sampling time point.i. Exact 2-sided CI based on the Clopper and Pearson method.j. Adjusted difference in proportions, based on the Miettinen and Nurminen stratified by baseline neutralisingtitre category (< median, ≥ median), expressed as a percentage Comirnaty (Bivalent BA.4-5) [3 mcg] -

Comirnaty [3 mcg). The median of baseline neutralising titres was calculated based on the pooled data in 2comparator groups.

k. 2-sided CI based on the Miettinen and Nurminen method for the difference in proportions stratified bybaseline neutralising titre category (< median, ≥ median), expressed as a percentage.

l. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the difference in percentages ofparticipants with seroresponse is > -5%.

m. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the difference in percentages ofparticipants with seroresponse is > -10%.

Immunogenicity in children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after the booster(fourth dose)

In an analysis of a subset from Study 6, 103 participants 5 to 11 years of age who had previouslyreceived a 2-dose primary series and booster dose with Comirnaty received a booster (fourth dose) of

Comirnaty Original/Omicron BA.4-5. Results include immunogenicity data from a comparator subsetof participants 5 to 11 years of age in Study 3 who received 3 doses of Comirnaty. In participants 5 to11 years of age who received a fourth dose of Comirnaty Original/Omicron BA.4-5 and participants 5to 11 years of age who received a third dose of Comirnaty, 57.3% and 58.4% were positive for

SARS-CoV-2 at baseline, respectively.

The immune response 1 month after a booster dose (fourth dose), Comirnaty Original/Omicron

BA.4-5 elicited generally similar Omicron BA.4/BA.5-specific neutralising titres compared with thetitres in the comparator group who received 3 doses of Comirnaty. Comirnaty Original/Omicron

BA.4-5 also elicited similar reference strain-specific titres compared with the titres in the comparatorgroup.

The vaccine immunogenicity results after a booster dose in participants 5 to 11 years of age arepresented in Table 4.

Table 4. Study 6 - Geometric mean ratio and Geometric mean titres - participants with orwithout evidence of infection - 5 to 11 years of age - evaluable immunogenicitypopulation

Vaccine group (as assigned/randomised)

Study 6

Comirnaty(Original/Omicron Study 3 Study 6

BA.4/BA.5) Comirnaty Comirnaty10 mcg 10 mcg (Original/Omicron

Dose 4 and Dose 3 and BA.4/BA.5)/Comirnaty

SARS-CoV-2 Sampling 1 month after Dose 4 1 month after Dose 3 10 mcgneutralisation time GMTc GMTc GMRdassay pointa nb (95% CIc) nb (95% CIc) (95% CId)

Omicron Pre- 488.3 248.3

BA.4-5 - NT50 vaccination 102 (361.9, 658.8) 112 (187.2, 329.5) -(titre)e 2 189.9 1 393.6 1.121 month 102 (1 742.8, 2 751.7) 113 (1 175.8, 1 651.7) (0.92, 1.37)

Reference Pre- 2 904.0 1 323.1strain - NT50 vaccination 102 (2 372.6, 3 554.5) 113 (1 055.7, 1 658.2) -(titre)e 8 245.9 7 235.11 month 102 (7 108.9, 9 564.9) 113 (6 331.5, 8 267.8) -

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; LS = least square; N-binding = SARS-CoV-2 nucleoprotein-binding;

NT50 = 50% neutralising titre; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

a. Protocol-specified timing for blood sample collection.

b. n = Number of participants with valid and determinate assay results for the specified assay at the givensampling time point.

c. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

d. GMRs and 2-sided CIs were calculated by exponentiating the difference of LS Means for the assay and thecorresponding CIs based on analysis of log-transformed assay results using a linear regression model withbaseline log-transformed neutralising titres, postbaseline infection status, and vaccine group as covariates.

e. SARS-CoV-2 NT50 were determined using a validated 384-well assay platform (original strain [USA-

WA1/2020, isolated in January 2020] and Omicron B.1.1.529 subvariant BA.4/BA.5).

Immunogenicity in participants 12 years of age and older - after the booster (fourth dose)

In an analysis of a subset from Study 5, 105 participants 12 to 17 years of age, 297 participants 18 to55 years of age, and 286 participants 56 years of age and older who had previously received a 2-doseprimary series and booster dose with Comirnaty received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5. In participants 12 to 17 years of age, 18 to 55 years of age, and 56 years ofage and older, 75.2%, 71.7% and 61.5% were positive for SARS-CoV-2 at baseline, respectively.

Analyses of 50% neutralising antibody titres (NT50) against Omicron BA.4-5 and against referencestrain among participants 56 years of age and older who received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5 in Study 5 compared to a subset of participants from Study 4 who receiveda booster (fourth dose) of Comirnaty demonstrated superiority of Comirnaty Original/Omicron BA.4-5to Comirnaty based on geometric mean ratio (GMR) and noninferiority based on difference inseroresponse rates with respect to anti-Omicron BA.4-5 response, and noninferiority of anti-referencestrain immune response based on GMR (Table 5).

Analyses of NT50 against Omicron BA.4/BA.5 among participants 18 to 55 years of age compared toparticipants 56 years of age and older who received a booster (fourth dose) of Comirnaty

Original/Omicron BA.4-5 in Study 5 demonstrated noninferiority of anti-Omicron BA.4-5 responseamong participants 18 to 55 years of age compared to participants 56 years of age and older for both

GMR and difference in seroresponse rates (Table 5).

The study also assessed the level of NT50 of the anti-Omicron BA.4-5 SARS-CoV-2 and referencestrains pre-vaccination and 1 month after vaccination in participants who received a booster (fourthdose) (Table 6).

Table 5. SARS-CoV-2 GMTs (NT50) and difference in percentages of participants withseroresponse at 1 month after vaccination course - Comirnaty Original/Omicron

BA.4-5 from Study 5 and Comirnaty from subset of Study 4 - participants with orwithout evidence of SARS-CoV-2 infection - evaluable immunogenicity population

SARS-CoV-2 GMTs (NT50) at 1 month after vaccination course

Study 5

Comirnaty Subset of Study 4 Age group Vaccine group

Original/Omicron BA.4-5 Comirnaty comparison comparison

Comirnaty

Original/ ≥ 56 years of age

Omicron BA.4-5 Comirnaty18 to 55 years of Original/18 to 55 years of 56 years of age 56 years of age age/≥ 56 years of Omicron BA.4-5age and older and older age /Comirnaty

SARS-CoV-2 GMTbneutralisation GMTc (95% GMTb GMRc GMRcassay na (95% CIc) na CIb) na (95% CIb) (95% CIc) (95% CIc)

Omicron BA.4-5 - 4 455.9 4 158.1 938.9

NT50 (titre)d 297 (3 851.7, 284 (3 554.8, 282 (802.3, 0.98 2.91e5 154.8) 4 863.8) 1 098.8) (0.83, 1.16) (2.45, 3.44)f

Reference Strain - 16 250.1 10 415.5

NT50 (titre)d - - 286 (14 499.2, 289 (9 366.7, - 1.38g18 212.4) 11 581.8) (1.22, 1.56)

Difference in percentages of participants with seroresponse at 1 month after vaccination course

Comirnaty Subset of Study 4 Age group Vaccine group

Original/Omicron BA.4-5 Comirnaty comparison comparison≥ 56 years of age

Comirnaty18 to 55 years of 56 years of age 56 years of age Original/Omicro Comirnatyage and older and older n BA.4-5 Original/18 to 55 years of Omicron BA.4-5age/≥ 56 /Comirnaty

SARS-CoV-2 iineutralisation Nh n (%) n (%) i

Nh (95% Nh n (%) Differencek Differencekk jassay (95% CI ) CIk) (95% CI ) (95% CIl) (95% CIl)

Omicron BA.4-5 - 294 180 (61.2) 188 (66.7) 127 (46.5) -3.03 26.77

NT50 (titre)d (55.4, 282 (60.8, 273 (40.5, 52.6) (-9.68, 3.63)m (19.59, 33.95)n66.8) 72.1)

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; LS = least square; NT50 = 50% neutralising titre; SARS-CoV-2 = severeacute respiratory syndrome coronavirus 2.

Note: Seroresponse is defined as achieving a ≥ 4-fold rise from baseline. If the baseline measurement is belowthe LLOQ, a post-vaccination assay result ≥ 4 × LLOQ is considered a seroresponse.

a. n = Number of participants with valid and determinate assay results for the specified assay at the givensampling time point.

b. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

c. GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of LS means andcorresponding CIs based on analysis of logarithmically transformed neutralising titres using a linearregression model with terms of baseline neutralising titre (log scale) and vaccine group or age group.

d. SARS-CoV-2 NT50 were determined using a validated 384-well assay platform (original strain[USA-WA1/2020, isolated in January 2020] and Omicron B.1.1.529 subvariant BA.4/BA.5).

e. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 0.67.

f. Superiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 1.g. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 0.67 and thepoint estimate of the GMR is ≥ 0.8.h. N = Number of participants with valid and determinate assay results for the specified assay at both the pre-vaccination time point and the given sampling time point. This value is the denominator for the percentagecalculation.

i. n = Number of participants with seroresponse for the given assay at the given sampling time point.j. Exact 2-sided CI, based on the Clopper and Pearson method.k. Difference in proportions, expressed as a percentage.l. 2-sided CI based on the Miettinen and Nurminen method stratified by baseline neutralising titre category(< median, ≥ median) for the difference in proportions. The median of baseline neutralising titres wascalculated based on the pooled data in 2 comparator groups.

m. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the difference in percentages ofparticipants with seroresponse is > -10%.

n. Noninferiority is declared if the lower bound of the 2-sided 95% CI for the difference in percentages ofparticipants with seroresponse is > -5%.

Table 6. Geometric mean titres - Comirnaty Original/Omicron BA.4-5 subsets of Study 5 -prior to and 1 month after booster (fourth dose) - participants 12 years of age andolder - with or without evidence of infection - evaluable immunogenicity population

Comirnaty

Original/Omicron BA.4-5

SARS-CoV-2 12 to 17 years of age 18 to 55 years of age 56 years of age and olderneutralisation Sampling GMTc GMTc GMTcassay time pointa nb (95% CIc) nb (95% CIc) nb (95% CIc)

Pre- 1 105.8 569.6 458.2

Omicron BA.4-5 vaccination 104 (835.1, 1 464.3) 294 (471.4, 688.2) 284 (365.2, 574.8)

- NT50 (titre)d 8 212.8(6 807.3, 4 455.9 4 158.11 month 105 9 908.7) 297 (3 851.7, 5 154.8) 284 (3 554.8, 4 863.8)6 863.3

Pre- (5 587.8, 4 017.3 3 690.6

Reference strain vaccination 105 8 430.1) 296 (3 430.7, 4 704.1) 284 (3 082.2, 4 419.0)- NT50 (titre)d 23 641.3(20 473.1, 16 323.3 16 250.11 month 105 27 299.8) 296 (14 686.5, 18 142.6) 286 (14 499.2, 18 212.4)

Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit of quantitation;

NT50 = 50% neutralising titre; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

a. Protocol-specified timing for blood sample collection.

b. n = Number of participants with valid and determinate assay results for the specified assay at the givensampling time point.

c. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

d. SARS-CoV-2 NT50 were determined using a validated 384-well assay platform (original strain[USA-WA1/2020, isolated in January 2020] and Omicron B.1.1.529 subvariant BA.4-5).

Comirnaty

Study 2 is a multicentre, multinational, Phase 1/2/3 randomised, placebo-controlled, observer-blinddose-finding, vaccine candidate selection and efficacy study in participants 12 years of age and older.

Randomisation was stratified by age: 12 to 15 years of age, 16 to 55 years of age, or 56 years of ageand older, with a minimum of 40% of participants in the ≥ 56-year stratum. The study excludedparticipants who were immunocompromised and those who had previous clinical or microbiologicaldiagnosis of COVID-19. Participants with pre-existing stable disease, defined as disease not requiringsignificant change in therapy or hospitalisation for worsening disease during the 6 weeks beforeenrolment, were included as were participants with known stable infection with humanimmunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV).

In the Phase 2/3 portion of Study 2, based on data accrued through 14 November 2020, approximately44 000 participants were randomised equally and were to receive 2 doses of the initially approved

COVID-19 mRNA Vaccine or placebo. The efficacy analyses included participants that received theirsecond vaccination within 19 to 42 days after their first vaccination. The majority (93.1%) of vaccinerecipients received the second dose 19 days to 23 days after Dose 1. Participants are planned to befollowed for up to 24 months after Dose 2, for assessments of safety and efficacy against COVID-19.

In the clinical study, participants were required to observe a minimum interval of 14 days before andafter administration of an influenza vaccine in order to receive either placebo or COVID-19 mRNA

Vaccine. In the clinical study, participants were required to observe a minimum interval of 60 daysbefore or after receipt of blood/plasma products or immunoglobulins within through conclusion of thestudy in order to receive either placebo or COVID-19 mRNA Vaccine.

The population for the analysis of the primary efficacy endpoint included 36 621 participants 12 yearsof age and older (18 242 in the COVID-19 mRNA Vaccine group and 18 379 in the placebo group)who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose.

In addition, 134 participants were between the ages of 16 to 17 years of age (66 in the COVID-19mRNA Vaccine group and 68 in the placebo group) and 1 616 participants 75 years of age and older(804 in the COVID-19 mRNA Vaccine group and 812 in the placebo group).

At the time of the primary efficacy analysis, participants had been followed for symptomatic

COVID-19 for in total 2 214 person-years for the COVID-19 mRNA Vaccine and in total2 222 person-years in the placebo group.

There were no meaningful clinical differences in overall vaccine efficacy in participants who were atrisk of severe COVID-19 including those with 1 or more comorbidities that increase the risk of severe

COVID-19 (e.g. asthma, body mass index (BMI) ≥ 30 kg/m2, chronic pulmonary disease, diabetesmellitus, hypertension).

The vaccine efficacy information is presented in Table 7.

Table 7. Vaccine efficacy - First COVID-19 occurrence from 7 days after Dose 2, by agesubgroup - participants without evidence of infection prior to 7 days after

Dose 2 - evaluable efficacy (7 days) population

First COVID-19 occurrence from 7 days after Dose 2 in participants without evidence ofprior SARS-CoV-2 infection*

COVID-19 mRNA

Vaccine Placebo

Na = 18 198 Na = 18 325

Cases Casesn1b n1b Vaccine efficacy %

Subgroup Surveillance timec (n2d) Surveillance timec (n2d) (95% CI)e8 162 95.0

All participants 2.214 (17 411) 2.222 (17 511) (90.0, 97.9)7 143 95.116 to 64 years 1.706 (13 549) 1.710 (13 618) (89.6, 98.1)1 19 94.765 years and older 0.508 (3 848) 0.511 (3 880) (66.7, 99.9)1 14 92.965 to 74 years 0.406 (3 074) 0.406 (3 095) (53.1, 99.8)75 years and 0 5 100.0older 0.102 (774) 0.106 (785) (-13.1, 100.0)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and atleast 1 symptom consistent with COVID-19 [*Case definition: (at least 1 of) fever, new or increased cough, newor increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat,diarrhoea or vomiting.]

* Participants who had no serological or virological evidence (prior to 7 days after receipt of the last dose) ofpast SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 notdetected by nucleic acid amplification tests (NAAT) [nasal swab] at Visits 1 and 2), and had negative NAAT(nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis.

a. N = Number of participants in the specified group.

b. n1 = Number of participants meeting the endpoint definition.

c. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of thesurveillance period.

d. n2 = Number of participants at risk for the endpoint.

e. Two-sided confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson methodadjusted to the surveillance time. CI not adjusted for multiplicity.

Dose 2 compared to placebo was 94.6% (95% confidence interval of 89.6% to 97.6%) in participants16 years of age and older with or without evidence of prior infection with SARS-CoV-2.

Additionally, subgroup analyses of the primary efficacy endpoint showed similar efficacy pointestimates across genders, ethnic groups, and participants with medical comorbidities associated withhigh risk of severe COVID-19.

Updated efficacy analyses were performed with additional confirmed COVID-19 cases accrued duringblinded placebo-controlled follow-up, representing up to 6 months after Dose 2 in the efficacypopulation.

The updated vaccine efficacy information is presented in Table 8.

Table 8. Vaccine efficacy - First COVID-19 occurrence from 7 days after Dose 2, by agesubgroup - participants without evidence of prior SARS-CoV-2 infection* prior to7 days after Dose 2 - evaluable efficacy (7 days) population during theplacebo-controlled follow-up period

COVID-19 mRNA

Vaccine Placebo

Na=20 998 Na=21 096

Cases Casesn1b n1b Vaccine efficacy

Surveillance timec Surveillance timec %

Subgroup (n2d) (n2d) (95% CIe)77 850 91.3

All participantsf 6.247 (20 712) 6.003 (20 713) (89.0, 93.2)70 710 90.616 to 64 years 4.859 (15 519) 4.654 (15 515) (87.9, 92.7)7 124 94.565 years and older 1.233 (4 192) 1.202 (4 226) (88.3, 97.8)6 98 94.165 to 74 years 0.994 (3 350) 0.966 (3 379) (86.6, 97.9)1 26 96.275 years and older 0.239 (842) 0.237 (847) (76.9, 99.9)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and atleast 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new orincreased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat;diarrhoea; vomiting).

* Participants who had no evidence of past SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative at

Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT(nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis.

a. N = Number of participants in the specified group.

b. n1 = Number of participants meeting the endpoint definition.

c. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of thesurveillance period.

d. n2 = Number of participants at risk for the endpoint.

e. Two-sided 95% confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearsonmethod adjusted to the surveillance time.

f. Included confirmed cases in participants 12 to 15 years of age: 0 in the COVID-19 mRNA Vaccine group; 16in the placebo group.

In the updated efficacy analysis, efficacy of COVID-19 mRNA Vaccine in preventing first COVID-19occurrence from 7 days after Dose 2 compared to placebo was 91.1% (95% CI of 88.8% to 93.0%)during the period when Wuhan/wild-type and Alpha variants were the predominant circulating strainsin participants in the evaluable efficacy population with or without evidence of prior infection with

SARS-CoV-2.

Additionally, the updated efficacy analyses by subgroup showed similar efficacy point estimatesacross sexes, ethnic groups, geography and participants with medical comorbidities and obesityassociated with high risk of severe COVID-19.

Updated efficacy analyses of secondary efficacy endpoints supported benefit of the COVID-19 mRNA

Vaccine in preventing severe COVID‑19.

As of 13 March 2021, vaccine efficacy against severe COVID-19 is presented only for participantswith or without prior SARS-CoV-2 infection (Table 9) as the COVID-19 case counts in participantswithout prior SARS-CoV-2 infection were the same as those in participants with or without prior

SARS-CoV-2 infection in both the COVID-19 mRNA Vaccine and placebo groups.

Table 9. Vaccine efficacy - First severe COVID-19 occurrence in participants with or withoutprior SARS-CoV-2 infection based on the Food and Drug Administration (FDA)*after Dose 1 or from 7 days after Dose 2 in the placebo-controlled follow-up

COVID-19 mRNA

Vaccine Placebo

Cases Casesn1a n1a Vaccine efficacy %

Surveillance time (n2b) Surveillance time (n2b) (95% CIc)1 30 96.7

After Dose 1d 8.439e (22 505) 8.288e (22 435) (80.3, 99.9)1 21 95.37 days after Dose 2f 6.522g (21 649) 6.404g (21 730) (70.9, 99.9)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and atleast 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new orincreased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat;diarrhoea; vomiting).

* Severe illness from COVID-19 as defined by FDA is confirmed COVID-19 and presence of at least 1 of thefollowing:

* Clinical signs at rest indicative of severe systemic illness (respiratory rate ≥ 30 breaths per minute, heartrate ≥ 125 beats per minute, saturation of oxygen ≤ 93% on room air at sea level, or ratio of arterialoxygen partial pressure to fractional inspired oxygen < 300 mm Hg);

* Respiratory failure [defined as needing high-flow oxygen, noninvasive ventilation, mechanicalventilation or extracorporeal membrane oxygenation (ECMO)];

* Evidence of shock (systolic blood pressure < 90 mm Hg, diastolic blood pressure < 60 mm Hg, orrequiring vasopressors);

* Significant acute renal, hepatic, or neurologic dysfunction;

* Admission to an Intensive Care Unit;

* Death.

a. n1 = Number of participants meeting the endpoint definition.

b. n2 = Number of participants at risk for the endpoint.

c. Two-side confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson methodadjusted to the surveillance time.

d. Efficacy assessed based on the Dose 1 all available efficacy (modified intention-to-treat) population thatincluded all randomised participants who received at least 1 dose of study intervention.

e. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from Dose 1 to the end of thesurveillance period.

f. Efficacy assessed based on the evaluable efficacy (7 Days) population that included all eligible randomisedparticipants who receive all dose(s) of study intervention as randomised within the predefined window, haveno other important protocol deviations as determined by the clinician.

g. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of thesurveillance period.

In an initial analysis of Study 2 in adolescents 12 to 15 years of age (representing a median follow-upduration of > 2 months after Dose 2) without evidence of prior infection, there were no cases in1 005 participants who received the vaccine and 16 cases out of 978 who received placebo. The pointestimate for efficacy is 100% (95% confidence interval 75.3, 100.0). In participants with or withoutevidence of prior infection there were 0 cases in the 1 119 who received vaccine and 18 cases in1 110 participants who received placebo. This also indicates the point estimate for efficacy is 100%(95% confidence interval 78.1, 100.0).

Updated efficacy analyses were performed with additional confirmed COVID-19 cases accrued duringblinded placebo-controlled follow-up, representing up to 6 months after Dose 2 in the efficacypopulation.

In the updated efficacy analysis of Study 2 in adolescents 12 to 15 years of age without evidence ofprior infection, there were no cases in 1 057 participants who received the vaccine and 28 cases out of1 030 who received placebo. The point estimate for efficacy is 100% (95% confidence interval 86.8,100.0) during the period when Alpha variant was the predominant circulating strain. In participantswith or without evidence of prior infection there were 0 cases in the 1 119 who received vaccine and30 cases in 1 109 participants who received placebo. This also indicates the point estimate for efficacyis 100% (95% confidence interval 87.5, 100.0).

In Study 2, an analysis of SARS-CoV-2 neutralising titres 1 month after Dose 2 was conducted in arandomly selected subset of participants who had no serological or virological evidence of past

SARS-CoV-2 infection up to 1 month after Dose 2, comparing the response in adolescents 12 to15 years of age (n = 190) to participants 16 to 25 years of age (n = 170).

The ratio of the geometric mean titres (GMT) in the 12 to 15 years of age group to the 16 to 25 yearsof age group was 1.76, with a 2-sided 95% CI of 1.47 to 2.10. Therefore, the 1.5-fold noninferioritycriterion was met as the lower bound of the 2-sided 95% CI for the geometric mean ratio [GMR] was> 0.67.

Efficacy and immunogenicity in children 5 to 11 years of age (i.e. 5 to less than 12 years of age) -after 2 doses

Study 3 is a Phase 1/2/3 study comprised of an open-label vaccine dose-finding portion (Phase 1) anda multicentre, multinational, randomised, saline placebo-controlled, observer-blind efficacy portion(Phase 2/3) that has enrolled participants 5 to 11 years of age. The majority (94.4%) of randomisedvaccine recipients received the second dose 19 days to 23 days after Dose 1.

Initial descriptive vaccine efficacy results in children 5 to 11 years of age without evidence of prior

SARS-CoV-2 infection are presented in Table 10. No cases of COVID-19 were observed in either thevaccine group or the placebo group in participants with evidence of prior SARS-CoV-2 infection.

Table 10. Vaccine efficacy - First COVID-19 occurrence from 7 days after Dose 2: Withoutevidence of infection prior to 7 days after Dose 2 - Phase 2/3 - Children 5 to 11 yearsof age evaluable efficacy population

First COVID-19 occurrence from 7 days after Dose 2 in children 5 to 11 years of age withoutevidence of prior SARS-CoV-2 infection*

COVID-19 mRNA

Vaccine10 mcg/dose Placebo

Na=1 305 Na=663

Cases Casesn1b n1b Vaccine efficacy %

Surveillance timec (n2d) Surveillance timec (n2d) (95% CI)

Children 5 to 11 years of 3 16 90.7age 0.322 (1 273) 0.159 (637) (67.7, 98.3)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and atleast 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increasedshortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhoea;vomiting).

* Participants who had no evidence of past SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative at

Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT(nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis.

a. N = Number of participants in the specified group.

b. n1 = Number of participants meeting the endpoint definition.

c. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of thesurveillance period.

d. n2 = Number of participants at risk for the endpoint.

Pre-specified hypothesis-driven efficacy analysis was performed with additional confirmed

COVID-19 cases accrued during blinded placebo-controlled follow-up, representing up to 6 monthsafter Dose 2 in the efficacy population.

In the efficacy analysis of Study 3 in children 5 to 11 years of age without evidence of prior infection,there were 10 cases in 2 703 participants who received the vaccine and 42 cases out of 1 348 whoreceived placebo. The point estimate for efficacy is 88.2% (95% confidence interval 76.2, 94.7) duringthe period when Delta variant was the predominant circulating strain. In participants with or withoutevidence of prior infection there were 12 cases in the 3 018 who received vaccine and 42 cases in1 511 participants who received placebo. The point estimate for efficacy is 85.7% (95% confidenceinterval 72.4, 93.2).

In Study 3, an analysis of SARS-CoV-2 50% neutralising titres (NT50) 1 month after Dose 2 in arandomly selected subset of participants demonstrated effectiveness by immunobridging of immuneresponses comparing children 5 to 11 years of age (i.e. 5 to less than 12 years of age) in the Phase 2/3part of Study 3 to participants 16 to 25 years of age in the Phase 2/3 part of Study 2 who had noserological or virological evidence of past SARS-CoV-2 infection up to 1 month after Dose 2, meetingthe pre-specified immunobridging criteria for both the geometric mean ratio (GMR) and theseroresponse difference with seroresponse defined as achieving at least 4-fold rise in SARS-CoV-2

NT50 from baseline (before Dose 1).

The GMR of the SARS-CoV-2 NT50 1 month after Dose 2 in children 5 to 11 years of age (i.e. 5 toless than 12 years of age) to that of young adults 16 to 25 years of age was 1.04 (2-sided 95% CI: 0.93,1.18). Among participants without prior evidence of SARS-CoV-2 infection up to 1 month after

Dose 2, 99.2% of children 5 to 11 years of age and 99.2% of participants 16 to 25 years of age had aseroresponse at 1 month after Dose 2. The difference in proportions of participants who hadseroresponse between the 2 age groups (children - young adult) was 0.0% (2-sided 95% CI: -2.0%,2.2%). This information is presented in Table 11.

Table 11. Summary of geometric mean ratio for 50% neutralising titre and difference inpercentages of participants with seroresponse - comparison of children 5 to 11 yearsof age (Study 3) to participants 16 to 25 years of age (Study 2) - participants withoutevidence of infection up to 1 month after Dose 2 - immunobridging subset -

Phase 2/3 - evaluable immunogenicity population

COVID-19 mRNA Vaccine10 mcg/dose 30 mcg/dose5 to 11 years 16 to 25 years 5 to 11 years/

Na=264 Na=253 16 to 25 years

Metimmunobridging

Time GMTc GMTc GMRd objectiveepointb (95% CIc) (95% CIc) (95% CId) (Y/N)

Geometricmean 50% 1 monthneutralising after 1 197.6 1 146.5 1.04titref (GMTc) Dose 2 (1 106.1, 1 296.6) (1 045.5, 1 257.2) (0.93, 1.18) Y

Met

Difference immunobridging

Time ng (%) ng (%) %i objectivekpointb (95% CIh) (95% CIh) (95% CIj) (Y/N)

Seroresponserate (%) for50% 1 monthneutralising after 262 (99.2) 251 (99.2) 0.0titref Dose 2 (97.3, 99.9) (97.2, 99.9) (-2.0, 2.2) Y

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; NAAT = nucleic acid amplification test; NT50 = 50% neutralising titre;

SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Note: Participants who had no serological or virological evidence (up to 1 month post-Dose 2 blood samplecollection) of past SARS-CoV-2 infection (i.e. N-binding antibody [serum] negative at Dose 1 visit and 1 monthafter Dose 2, SARS-CoV-2 not detected by NAAT [nasal swab] at Dose 1 and Dose 2 visits, and negative NAAT(nasal swab) at any unscheduled visit up to 1 month after Dose 2 blood collection) and had no medical history of

COVID-19 were included in the analysis.

Note: Seroresponse is defined as achieving a ≥ 4-fold rise from baseline (before Dose 1). If the baselinemeasurement is below the LLOQ, a post-vaccination assay result ≥ 4 × LLOQ is considered a seroresponse.

a. N = Number of participants with valid and determinate assay results before vaccination and at 1 month after

Dose 2. These values are also the denominators used in the percentage calculations for seroresponse rates.

b. Protocol-specified timing for blood sample collection.

c. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

d. GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of thetitres (5 to 11 years of age minus 16 to 25 years of age) and the corresponding CI (based on the Student tdistribution).

e. Immunobridging based on GMT is declared if the lower bound of the 2-sided 95% CI for the GMR is greaterthan 0.67 and the point estimate of the GMR is ≥ 0.8.

f. SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralisation

Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virusneutralisation is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilutionat which 50% of the virus is neutralised.

g. n = Number of participants with seroresponse based on NT50 1 month after Dose 2.h. Exact 2-sided CI based on the Clopper and Pearson method.i. Difference in proportions, expressed as a percentage (5 to 11 years of age minus 16 to 25 years of age).j. 2-Sided CI, based on the Miettinen and Nurminen method for the difference in proportions, expressed as apercentage.k. Immunobridging based on seroresponse rate is declared if the lower bound of the 2-sided 95% CI for theseroresponse difference is greater than -10.0%.

Immunogenicity in children 5 to 11 years of age (i.e. 5 to less than 12 years of age) - after boosterdose

A booster dose of Comirnaty was given to 401 randomly selected participants in Study 3.

Effectiveness of a booster dose in ages 5 to 11 is inferred by immunogenicity. The immunogenicity ofthis was assessed through NT50 against the reference strain of SARS-CoV-2 (USA_WA1/2020).

Analyses of NT50 1 month after the booster dose compared to before the booster dose demonstrated asubstantial increase in GMTs in individuals 5 to 11 years of age who had no serological or virologicalevidence of past SARS-CoV-2 infection up to 1 month after the dose 2 and the booster dose. Thisanalysis is summarised in Table 12.

Table 12. Summary of geometric mean titres - NT50 - participants without evidence ofinfection - phase 2/3 - immunogenicity set - 5 to 11 years of age - evaluableimmunogenicity population

Sampling time pointa1 month after booster1 month after booster 1 month after dose 2 dose/dose (nb=67) (nb=96) 1 month after dose 2

GMTc GMTc GMRd

Assay (95% CIc) (95% CIc) (95% CId)

SARS-CoV-2neutralisation assay - 2 720.9 1 253.9 2.17

NT50 (titre) (2 280.1, 3 247.0) (1 116.0, 1 408.9) (1.76, 2.68)

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; NT50 = 50% neutralising titre; SARS-CoV-2 = severe acute respiratorysyndrome coronavirus 2.

a. Protocol-specified timing for blood sample collection.

b. n = Number of participants with valid and determinate assay results for the specified assay at the givendose/sampling time point.

c. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

d. GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of thetitres (1-Month Post-Booster Dose minus 1-Month Post-Dose 2) and the corresponding CI (based on the

Student t distribution).

Efficacy and immunogenicity of a 3-dose primary course in infants and children 6 months to 4 years ofage

The efficacy analysis of Study 3 was performed across the combined population of participants6 months to 4 years of age based on cases confirmed among 873 participants in the COVID-19 mRNA

Vaccine group and 381 participants in the placebo group (2:1 randomisation ratio) who received all3 doses of study intervention during the blinded follow-up period when the Omicron variant of

SARS−CoV−2 (BA.2) was the predominant variant in circulation (data cut-off date of 17 June 2022).

The vaccine efficacy results after Dose 3 in participants 6 months to 4 years of age are presented in

Table 13.

Table 13. Vaccine efficacy - first COVID-19 occurrence from 7 days after Dose 3 - blindedfollow-up period - participants without evidence of infection prior to 7 days after

Dose 3 - phase 2/3 - 6 months to 4 years of age - evaluable efficacy (3-dose)population

First COVID-19 occurrence from 7 days after Dose 3 in participants without evidence of prior

SARS-CoV-2 infection*

COVID-19 mRNA

Vaccine 3 mcg/Dose Placebo

Na=873 Na=381

Cases Casesn1b n1b Vaccine Efficacy %

Subgroup Surveillance Timec (n2d) Surveillance Timec (n2d) (95% CIe)13 21 73.26 months to 4 yearse 0.124 (794) 0.054 (351) (43.8, 87.6)9 13 71.82 to 4 years 0.081 (498) 0.033 (204) (28.6, 89.4)6 months to 4 8 75.823 months 0.042 (296) 0.020 (147) (9.7, 94.7)

Abbreviations: NAAT = nucleic acid amplification test; N-binding = SARS-CoV-2 nucleoprotein-binding;

SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; VE = vaccine efficacy.

* Participants who had no serological or virological evidence (prior to 7 days after receipt of Dose 3) of past

SARS-CoV-2 infection (i.e. negative N-binding antibody [serum] result at Dose 1, 1 month post-Dose 2 (ifavailable), Dose 3 (if available) visits, SARS-CoV-2 not detected by NAAT [nasal swab] at Dose 1, Dose 2,and Dose 3 study visits, and a negative NAAT [nasal swab] result at any unscheduled visit prior to 7 daysafter receipt of Dose 3) and had no medical history of COVID-19 were included in the analysis.

a. N = number of participants in the specified group.

b. n1 = Number of participants meeting the endpoint definition.

c. Total surveillance time in 1 000 person-years for the given endpoint across all participants within each groupat risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 3 to the end of thesurveillance period.

d. n2 = Number of participants at risk for the endpoint.

e. Two-sided 95% confidence interval (CI) for VE is derived based on the Clopper and Pearson methodadjusted for surveillance time.

Vaccine efficacy in participants with or without prior SARS-CoV-2 infection was similar to thoseparticipants without prior SARS-CoV-2 infection.

Severe COVID-19 criteria (as described in the protocol, based on FDA definition and modified forchildren) were fulfilled for 12 cases (8 COVID-19 mRNA Vaccine and 4 placebo) among participants6 months to 4 years of age. Among participants 6 months to 23 months of age, severe COVID-19criteria were fulfilled for 3 cases (2 COVID-19 mRNA Vaccine and 1 placebo).

Immunogenicity analyses have been performed in the immunobridging subset of 82 Study 3participants 6 to 23 months of age and 143 Study 3 participants 2 to 4 years of age without evidence ofinfection up to 1 month after Dose 3 based on a data cut-off date of 29 April 2022.

SARS-CoV-2 50% neutralising antibody titres (NT50) were compared between an immunogenicitysubset of Phase 2/3 participants 6 to 23 months of age and 2 to 4 years of age from Study 3 at 1 monthafter the 3-dose primary course and a randomly selected subset from Study 2 Phase 2/3 participants 16to 25 years of age at 1 month after the 2-dose primary course, using a microneutralisation assayagainst the reference strain (USA_WA1/2020).

The primary immunobridging analyses compared the geometric mean titres (using a geometric meanratio [GMR]) and the seroresponse (defined as achieving at least 4-fold rise in SARS-CoV-2 NT50from before Dose 1) rates in the evaluable immunogenicity population of participants withoutevidence of prior SARS-CoV-2 infection up to 1 month after Dose 3 in participants 6 to 23 months ofage and 2 to 4 years of age and up to 1 month after Dose 2 in participants 16 to 25 years of age. Thepre-specified immunobridging criteria were met for both the GMR and the seroresponse difference forboth age groups (Table 14).

Table 14. SARS-CoV-2 GMTs (NT50) and difference in percentages of participants withseroresponse at 1 month after vaccination course - immunobridging subset -participants 6 months to 4 years of age (Study 3) 1 month after Dose 3 andparticipants 16 to 25 years of age (Study 2) 1 month after Dose 2 - without evidenceof SARS-CoV-2 infection - evaluable immunogenicity population

SARS-CoV-2 GMTs (NT50) at 1 month after vaccination course

SARS-CoV-2 neutralisation assay - NT50 (titre)e

GMTb GMTb(95% CIb) (95% CIb)(1 month after (1 month after GMRc,d

Age Na Dose 3) Age Na Dose 2) Age (95% CI)2 to16 to 1 180.0 4 years/16 to1 535.2 25 years (1 066.6, 25 years of 1.302 to 4 years 143 (1 388.2, 1 697.8) of age 170 1 305.4) age (1.13, 1.50)6 to23 months16 to 1 180.0 years/16 to6 to 1 406.5 25 years (1 066.6, 25 years of 1.1923 months 82 (1 211.3, 1 633.1) of age 170 1 305.4) age (1.00, 1.42)

Difference in percentages of participants with seroresponse at 1 month after vaccination course

SARS-CoV-2 neutralisation assay - NT50 (titre)enf (%) nf (%) Difference in(95% CIg) (95% CIg) seroresponse(1 month after (1 month after rates %h

Age Na Dose 3) Age Na Dose 2) Age (95% CIi)j2 to16 to 4 years/16 to141(100.0) 25 years 168 (98.8) 25 years of 1.22 to 4 years 141 (97.4, 100.0) of age 170 (95.8, 99.9) age (1.5, 4.2)6 to23 months16 to years/16 to6 to 80 (100.0) 25 years 168 (98.8) 25 years of 1.223 months 80 (95.5, 100.0) of age 170 (95.8, 99.9) age (3.4, 4.2)

Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;

LLOQ = lower limit of quantitation; NAAT = nucleic acid amplification test; N-binding = SARS-CoV-2nucleoprotein-binding; NT50 = 50% neutralising titre; SARS-CoV-2 = severe acute respiratory syndromecoronavirus 2.

Note: Participants who had no serological or virological evidence [(up to 1 month after Dose 2 (Study 2) or1 month after Dose 3 (Study 3) blood sample collection)] of past SARS-CoV-2 infection [(i.e. N-bindingantibody [serum] negative at Dose 1, Dose 3 (Study 3) and 1 month after Dose 2 (Study 2) or 1 month after

Dose 3 (Study 3), SARS-CoV-2 not detected by NAAT [nasal swab] at Dose 1, Dose 2, and Dose 3 (Study 3)study visits, and negative NAAT (nasal swab) at any unscheduled visit up to 1 month after Dose 2 (Study 2) or1 month after Dose 3 (Study 3) blood collection)] and had no medical history of COVID-19 were included in theanalysis.

Note: Seroresponse is defined as achieving a ≥ 4-fold rise from baseline (before Dose 1). If the baselinemeasurement is below the LLOQ, a post-vaccination assay result ≥ 4 × LLOQ is considered a seroresponse.

a. N = Number of participants with valid and determinate assay results for the specified assay at the givendose/sampling time point for GMTs and number of participants with valid and determinate assay results forthe specified assay at both baseline and the given dose/sampling time point for seroresponse rates.

b. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and thecorresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to0.5 × LLOQ.

c. GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of thetitres (younger age group minus 16 to 25 years of age) and the corresponding CI (based on the

Student t distribution).

d. For each younger age group (2 to 4 years, 6 to 23 months), immunobridging based on GMR is declared if thelower bound of the 2-sided 95% CI for the GMR ratio is greater than 0.67 and the point estimate of the GMRis ≥ 0.8.

e. SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralisation

Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virusneutralisation is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilutionat which 50% of the virus is neutralised.

f. n = Number of participants with seroresponse for the given assay at the given dose/sampling time point.g. Exact 2-sided CI based on the Clopper and Pearson method.h. Difference in proportions, expressed as a percentage (younger age group minus 16 to 25 years of age).i. 2-sided CI, based on the Miettinen and Nurminen method for the difference in proportions, expressed as apercentage.j. For each younger age group (2 to 4 years, 6 to 23 months), immunobridging based on seroresponse rate isdeclared if the lower bound of the 2-sided 95% CI for the difference in proportions is greater than -10.0%provided that the immunobridging criteria based on GMR were met.

Immunogenicity in immunocompromised participants (adults and children)

Study 10 is a Phase 2b, open-label study (n = 124) that enrolled immunocompromised participants 2 to< 18 years of age receiving immunomodulator therapy or who have undergone solid organ transplant(within the previous 3 months) and are on immunosuppression or who have undergone bone marrowor stem cell transplant at least 6 months prior to enrolment and in immunocompromised participants18 years of age and older treated for non-small cell lung cancer (NSCLC) or chronic lymphocyticleukaemia (CLL), receiving haemodialysis for secondary to end-stage renal disease, or receivingimmunomodulator therapy for an autoimmune inflammatory disorder. Participants received4 age-appropriate doses of Comirnaty (3 mcg, 10 mcg, or 30 mcg); the first 2 doses separated by21 days, with the third dose occurring 28 days after the second dose, followed by a fourth dose, 3 to6 months after Dose 3.

Analysis of immunogenicity data at 1 month after Dose 3 (26 participants 2 to < 5 years of age,56 participants 5 to < 12 years of age, 11 participants 12 to < 18 years of age, and 4 participants≥ 18 years of age) and 1 month after Dose 4 (16 participants 2 to < 5 years of age, 31 participants 5 to< 12 years of age, 6 participants 12 to < 18 years of age, and 4 participants ≥ 18 years of age) in theevaluable immunogenicity population without evidence of prior infection demonstrated avaccine-elicited immune response. GMTs were observed to be substantially higher at 1 month after

Dose 3 and further increased at 1 month after Dose 4 and remained high at 6 months after Dose 4compared to levels observed before study vaccination across age groups and disease subsets.

The European Medicines Agency has deferred the obligation to submit the results of studies with

Comirnaty in the paediatric population in prevention of COVID-19 (see section 4.2 for information onpaediatric use).

Not applicable.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeat dosetoxicity and reproductive and developmental toxicity.

Rats intramuscularly administered Comirnaty (receiving 3 full human doses once weekly, generatingrelatively higher levels in rats due to body weight differences) demonstrated some injection siteoedema and erythema and increases in white blood cells (including basophils and eosinophils)consistent with an inflammatory response as well as vacuolation of portal hepatocytes withoutevidence of liver injury. All effects were reversible.

Neither genotoxicity nor carcinogenicity studies were performed. The components of the vaccine (lipidsand mRNA) are not expected to have genotoxic potential.

Reproductive and developmental toxicity were investigated in rats in a combined fertility anddevelopmental toxicity study where female rats were intramuscularly administered Comirnaty prior tomating and during gestation (receiving 4 full human doses that generate relatively higher levels in ratdue to body weight differences, spanning between pre-mating day 21 and gestational day 20).

SARS-CoV-2 neutralising antibody responses were present in maternal animals from prior to matingto the end of the study on post-natal day 21 as well as in foetuses and offspring. There were novaccine-related effects on female fertility, pregnancy, or embryo-foetal or offspring development. No

Comirnaty data are available on vaccine placental transfer or excretion in milk.

((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315)2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159)1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC)

Cholesterol

Trometamol

Trometamol hydrochloride

Sucrose

Water for injections

This medicinal product must not be mixed with other medicinal products except those mentioned insection 6.6.

The vaccine will be received frozen at −90 °C to −60 °C.

Frozen vaccine can be stored either at −90 °C to −60 °C or 2 °C to 8 °C upon receipt.

18 months when stored at −90 °C to −60 °C.

Within the 18-month shelf life the thawed (previously frozen) vials may be stored at 2 °C to 8 °C forup to 10 weeks.

Thawing procedure

When stored frozen at −90 °C to −60 °C, 10-vial packs of the vaccine can be thawed at 2 °C to 8 °Cfor:

* Orange cap: 4 hours

* Maroon cap or yellow cap: 2 hours

Individual vials can be thawed at room temperature (up to 30 °C) for 30 minutes.

Thawed (previously frozen) vials10 weeks storage and transportation at 2 °C to 8 °C within the 18-month shelf life.

* Upon moving the vaccine to 2 °C to 8 °C storage, the updated expiry date must be written onthe outer carton and the vaccine should be used or discarded by the updated expiry date. Theoriginal expiry date should be crossed out.

* If the vaccine is received at 2 °C to 8 °C it should be stored at 2 °C to 8 °C. The expiry date onthe outer carton should have been updated to reflect the refrigerated expiry date and the originalexpiry date should have been crossed out.

Prior to use, the unopened vials can be stored for up to 12 hours at temperatures between 8 °C and30 °C.

Thawed vials can be handled in room light conditions.

Once thawed, the vaccine should not be re-frozen.

Handling of temperature excursions during refrigerated storage

* Stability data indicate that the unopened vial is stable for up to 10 weeks when stored attemperatures from −2 °C to 2 °C, and within the 10-week storage period between 2 °C and 8 °C.

* Stability data indicate the vial can be stored for up to 24 hours at temperatures of 8 °C to 30 °C,including up to 12 hours following first puncture.

This information is intended to guide healthcare professionals only in case of temporary temperatureexcursion.

Chemical and physical in-use stability has been demonstrated for 12 hours at 2 ºC to 30 ºC, afterdilution with sodium chloride 9 mg/mL (0.9%) solution for injection, which includes up to 6 hourstransportation time. From a microbiological point of view, unless the method of dilution precludes therisk of microbial contamination, the product should be used immediately. If not used immediately,in-use storage times and conditions are the responsibility of the user.

Store in a freezer at −90 °C to −60 °C.

Store in the original package in order to protect from light.

During storage, minimise exposure to room light, and avoid exposure to direct sunlight and ultravioletlight.

For storage conditions after thawing and dilution of the medicinal product, see section 6.3.

Orange cap (10-dose vial)1.3 mL concentrate for dispersion in a 2 mL clear multidose vial (type I glass) with a stopper(synthetic bromobutyl rubber) and an orange flip-off plastic cap with aluminium seal. Each vialcontains 10 doses, see section 6.6.

Pack size: 10 vials

Maroon cap (10-dose vial)0.4 mL concentrate for dispersion in a 2 mL clear multidose vial (type I glass) with a stopper(synthetic bromobutyl rubber) and a maroon flip-off plastic cap with aluminium seal. Each vialcontains 10 doses, see section 6.6.

Pack size: 10 vials

Yellow cap (3-dose vial)0.48 mL concentrate for dispersion in a 2 mL clear multidose vial (type I glass) with a stopper(synthetic bromobutyl rubber) and a yellow flip-off plastic cap with aluminium seal. Each vialcontains 3 doses, see section 6.6.

Pack size: 10 vials

Orange cap (10-dose vial) or maroon cap (10-dose vial)

Handling instructions prior to use for a vial with an orange cap or maroon cap

Comirnaty Omicron XBB.1.5 should be prepared by a healthcare professional using aseptic techniqueto ensure the sterility of the prepared dispersion.

* Verify that the vial has either:

− an orange plastic cap and the product name is Comirnaty Omicron XBB.1.510 micrograms/dose concentrate for dispersion for injection (children 5 to 11 years),or− a maroon plastic cap and the product name is Comirnaty Omicron XBB.1.53 micrograms/dose concentrate for dispersion for injection (infants and children6 months to 4 years).

* If the vial has another product name on the label or a different cap colour, please make referenceto the Summary of Product Characteristics for that formulation.

* If the vial is stored frozen it must be thawed prior to use. Frozen vials should be transferred toan environment of 2 °C to 8 °C to thaw; a 10-vial pack may take:− Orange cap: 4 hours to thaw− Maroon cap: 2 hours to thaw

* Ensure vials are completely thawed prior to use.

* Upon moving vials to 2 °C to 8 °C storage, update the expiry date on the carton.

* Unopened vials can be stored for up to 10 weeks at 2 °C to 8 °C; not exceeding the printedexpiry date (EXP).

* Alternatively, individual frozen vials may be thawed for 30 minutes at temperatures up to 30 °C.

* Prior to use, the unopened vial can be stored for up to 12 hours at temperatures up to 30 °C.

Thawed vials can be handled in room light conditions.

Dilution for a vial with an orange cap or maroon cap

* Allow the thawed vial to come to room temperature and gently invert it 10 times prior todilution. Do not shake.

* Prior to dilution, the thawed dispersion may contain white to off-white opaque amorphousparticles.

* The thawed vaccine must be diluted in its original vial with:

− Orange cap: 1.3 mL sodium chloride 9 mg/mL (0.9%) solution for injection, using a21 gauge or narrower needle and aseptic techniques.

− Maroon cap: 2.2 mL sodium chloride 9 mg/mL (0.9%) solution for injection, using a21 gauge or narrower needle and aseptic techniques.

* Equalise vial pressure before removing the needle from the vial stopper by withdrawing air intothe empty diluent syringe.

* Gently invert the diluted dispersion 10 times. Do not shake.

* The diluted vaccine should present as a white to off-white dispersion with no particulatesvisible. Do not use the diluted vaccine if particulates or discolouration are present.

* The diluted vials should be marked with the appropriate discard date and time.

* After dilution, store at 2 ºC to 30 ºC and use within 12 hours.

* Do not freeze or shake the diluted dispersion. If refrigerated, allow the diluted dispersion tocome to room temperature prior to use.

Preparation of 0.2 mL doses using a vial with an orange cap or maroon cap

* After dilution, the vial contains 2.6 mL from which 10 doses of 0.2 mL can be extracted.

* Using aseptic technique, cleanse the vial stopper with a single use antiseptic swab.

* Withdraw 0.2 mL of Comirnaty Omicron XBB.1.5. Low dead-volume syringes and/orneedles should be used in order to extract 10 doses from a single vial. The low dead-volumesyringe and needle combination should have a dead-volume of no more than 35 microlitres. Ifstandard syringes and needles are used, there may not be sufficient volume to extract ten dosesfrom a single vial.

* Each dose must contain 0.2 mL of vaccine.

* If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard thevial and any excess volume.

* Discard any unused vaccine within 12 hours after dilution.

Yellow cap (3-dose vial)

Handling instructions prior to use for a vial with a yellow cap

Comirnaty Omicron XBB.1.5 should be prepared by a healthcare professional using aseptic techniqueto ensure the sterility of the prepared dispersion.

* Verify that the vial has a yellow plastic cap and the product name is Comirnaty Omicron

XBB.1.5 3 micrograms/dose concentrate for dispersion for injection (infants and children6 months to 4 years).

* If the vial has another product name on the label, or a different cap colour, please makereference to the Summary of Product Characteristics for that formulation.

* If the vial is stored frozen it must be thawed prior to use. Frozen vials should be transferred toan environment of 2 °C to 8 °C to thaw; a 10-vial pack may take 2 hours to thaw. Ensure vialsare completely thawed prior to use.

* Upon moving vials to 2 °C to 8 °C storage, update the expiry date on the carton.

* Unopened vials can be stored for up to 10 weeks at 2 °C to 8 °C; not exceeding the printedexpiry date (EXP).

* Alternatively, individual frozen vials may be thawed for 30 minutes at temperatures up to 30 °C.

* Prior to use, the unopened vial can be stored for up to 12 hours at temperatures up to 30 °C.

Thawed vials can be handled in room light conditions.

Dilution for a vial with a yellow cap

* Allow the thawed vial to come to room temperature and gently invert it 10 times prior todilution. Do not shake.

* Prior to dilution, the thawed dispersion may contain white to off-white opaque amorphousparticles.

* The thawed vaccine must be diluted in its original vial with 1.1 mL sodium chloride 9 mg/mL(0.9%) solution for injection, using a 21 gauge or narrower needle and aseptic techniques.

* Equalise vial pressure before removing the needle from the vial stopper by withdrawing 1.1 mLair into the empty diluent syringe.

* Gently invert the diluted dispersion 10 times. Do not shake.

* The diluted vaccine should present as a clear to slightly opalescent dispersion with noparticulates visible. Do not use the diluted vaccine if particulates or discolouration are present.

* The diluted vials should be marked with the appropriate discard date and time.

* After dilution, store at 2 ºC to 30 ºC and use within 12 hours.

* Do not freeze or shake the diluted dispersion. If refrigerated, allow the diluted dispersion tocome to room temperature prior to use.

Preparation of 0.3 mL doses using a vial with a yellow cap

* After dilution, the vial contains 1.58 mL from which 3 doses of 0.3 mL can be extracted.

* Using aseptic technique, cleanse the vial stopper with a single use antiseptic swab.

* Withdraw 0.3 mL of Comirnaty Omicron XBB.1.5 for infants and children aged 6 months to4 years. Standard syringes and/or needles can be used in order to extract 3 doses from a singlevial.

* Each dose must contain 0.3 mL of vaccine.

* If the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard thevial and any excess volume.

* Discard any unused vaccine within 12 hours after dilution.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

BioNTech Manufacturing GmbH

An der Goldgrube 1255131 Mainz

Germany

Phone: +49 6131 9084-0

Fax: +49 6131 9084-2121service@biontech.de

Orange cap (10-dose vial)

EU/1/20/1528/021

Maroon cap (10-dose vial)

EU/1/20/1528/024

Yellow cap (3-dose vial)

EU/1/20/1528/026

Date of first authorisation: 21 December 2020

Date of latest renewal: 10 October 2022

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu.