The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country.

GSK Medicine: FLU Q-PAN H9N2 (GSK2654911A and GSK2654909A)

Study Number: 116358 (FLU Q-PAN H9N2=AS03-001)

Title: An observer-blind study to evaluate the safety and immunogenicity of GSK Biologicals’ influenza vaccines GSK2654911A and GSK2654909A administered to adults 18 to 64 years of age. GSK2654911A (Q-PAN-1): GlaxoSmithKline (GSK) Biologicals’ Influenza A/chicken/Hong Kong/G9/1997 (H9N2) vaccine with adjuvant. GSK2654909A (Q-PAN-2): GSK Biologicals’ H9N2 vaccine without adjuvant. Rationale: The purpose of this study was to evaluate the immunogenicity and safety of different formulations of a 2-dose primary series and a booster vaccination of monovalent Influenza A/chicken/Hong Kong/G9/1997 (H9N2) vaccine manufactured in Quebec, Canada with and without adjuvant in adults 18 to 64 years of age, with a sub-analyses for subjects 18-40 years of age and 41-64 years of age.

Phase: I

Study Period: From 22 August 2012 to 19 March 2014

Study Design: Multi-center, randomized, placebo-controlled study with 11 parallel groups (1:1:1:1:1:1:1:1:1:1:4)

Centres: 3 centres in United States (U.S.) and 1 center in Canada

Indication: Immunization of healthy adults 18 to 64 years of age against H9N2 pandemic influenza

Treatment: The study groups were as follows:

Q-PAN-1A Group: Subjects in this group received 2 doses of formulation A of Q-PAN-1 vaccine at Days 0 and 21 and 1 dose of Q-PAN-1 vaccine or saline placebo at Day 182. ‒ Q-PAN-1A Group 1: Subjects in this group received 2 doses of formulation A of Q-PAN-1 vaccine at Days 0 and 21 and 1 dose

of saline placebo at Day 182. ‒ Q-PAN-1A Group 2: Subjects in this group received 3 doses of formulation A of Q-PAN-1 vaccine at Days 0, 21 and 182.

Q-PAN-1B Group: Subjects in this group received 2 doses of formulation B of Q-PAN-1 vaccine at Days 0 and 21 and 1 dose of Q-PAN-1 vaccine or saline placebo at Day 182. ‒ Q-PAN-1B Group 1: Subjects in this group received 2 doses of formulation B of Q-PAN-1 vaccine at Days 0 and 21 and 1 dose

of saline placebo at Day 182. ‒ Q-PAN-1B Group 2: Subjects in this group received 3 doses of formulation B of Q-PAN-1 vaccine at Days 0, 21 and 182.

Q-PAN-1C Group: Subjects in this group received 2 doses of formulation C of Q-PAN-1 vaccine at Days 0 and 21 and 1 dose of Q-PAN-1 vaccine or saline placebo at Day 182. ‒ Q-PAN-1C Group 1: Subjects in this group received 2 doses of formulation C of Q-PAN-1 vaccine at Days 0 and 21 and 1dose

of saline placebo at Day 182. ‒ Q-PAN-1C Group 2: Subjects in this group received 3 doses of formulation C of Q-PAN-1 vaccine at Days 0, 21 and 182.

Q-PAN-1D Group: Subjects in this group received 2 doses of formulation D of Q-PAN-1 vaccine at Days 0 and 21 and 1 dose of Q-PAN-1 vaccine or saline placebo at Day 182. ‒ Q-PAN-1D Group 1: Subjects in this group received 2 doses of formulation D of Q-PAN-1 vaccine at Days 0 and 21 and 1 dose

of saline placebo at Day 182. ‒ Q-PAN-1D Group 2: Subjects in this group received 3 doses of formulation C of Q-PAN-1 vaccine at Days 0, 21 and 182.

Q-PAN-2 Group: Subjects in this group received 2 doses of Q-PAN-2 vaccine at Days 0 and 21 and 1 dose of Q-PAN-2 vaccine or saline placebo at Day 182. ‒ Q-PAN-2 Group 1: Subjects in this group received 2 doses of Q-PAN-2 vaccine at Days 0 and 21 and 1 dose of saline placebo

at Day 182. ‒ Q-PAN-2 Group 2: Subjects in this group received 3 doses of Q-PAN-2 vaccine at Days 0, 21 and 182.

Placebo Group: Subjects in this group received 3 doses of saline placebo at Days 0, 21 and 182. Subjects received the respective vaccines, intramuscularly, in the deltoid region of non-dominant arm at Days 0 and 182 and in the dominant arm at Day 21.

Objectives:

To assess, in adults 18 to 64 years of age, whether vaccination with monovalent A/chicken/Hong Kong/G9/1997 (H9N2) vaccine, containing varying doses of hemagglutinin (HA) with adjuvant, resulted in an immune response to the vaccine-homologous virus that met or exceeded the U.S. Food and Drug Administration (FDA), Center for Biologics Evaluation and Research (CBER)* and the European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP)** guidance targets 21 days after the second or first dose of H9N2 vaccine

* The CBER criteria for immune response in persons < 65 years of age were met if:

the Lower Limit (LL) of 95% confidence interval (CI) for SCR met or exceeded 40%, and

the LL of 95% CI for SPR met or exceeded 70% **The CHMP criteria for immune response established for persons < 61 years of age were used for the entire study population and met if:

the point estimate for Seroconversion rates (SCR) > 40%, and

the point estimate for Seroprotection rates (SPR) > 70%, and

the Mean geometric increase (MGI) > 2.5

Primary Outcome/Efficacy Variable: Immunogenicity

For the humoral immune response in terms of hemaglutination inhibition (HI) antibodies against A/chicken/Hong Kong/G9/1997 (H9N2)v-like antigen the following aggregate variables were calculated for each group receiving adjuvanted vaccine:

‒ SCR* on Day 21 and Day 42 ‒ SPR** on Day 21 and Day 42 ‒ MGI*** on Day 21 and Day 42

*SCR was defined as the proportion of subjects that had either a pre-vaccination reciprocal HI titer <10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus. **SPR was defined as the proportion of subjects with reciprocal HI titers ≥ 40 against the tested vaccine virus. ***MGI was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus.

Secondary Outcome/Efficacy Variable(s): Immunogenicity

For the humoral immune response in terms of HI antibodies against A/chicken/Hong Kong/G9/1997 (H9N2) antigen the following aggregate variables were calculated for each vaccine group:

‒ Geometric Mean Titers (GMTs) and seropositivity rates on Days 0, 7, 21, 28, 42, 182, 191, 385 and 546 ‒ SCR on Days 7, 21 (Q-PAN-2 Group only), 42 (Q-PAN-2Group only), 28, 182, 191, 385, and 546 ‒ SPR on Days 0, 7, 21 (Q-PAN-2 Group only), 28, 42 (Q-PAN-2 Group only), 182, 191, 385 and 546 ‒ MGI on Days 7, 21 (Q-PAN-2 Group only), 28, 42 (Q-PAN-2Group only), 182, 191, 385, and 546 ‒ Booster seroconversion rate (B-SCR)* and booster factor (BF)**on Days 191, 385 and 546

For the humoral immune response in terms of HI antibodies against A/chicken/Hong Kong/G9/1997 (H9N2) antigen the following aggregate variables were calculated for each vaccine group and for age strata (18-40 years; 41-64 years):

‒ GMTs and seropositivity rates on Days 0, 7, 21, 28, 42, 182, 191, 385 and 546 ‒ SCR on Days 7, 21, 28, 42, 182, 191, 385 and 546 ‒ SPR on Days 0, 7, 21, 28, 42, 182, 191, 385 and 546 ‒ MGI on Days 7, 21, 28, 42, 182, 191, 385 and 546 ‒ B-SCR and BF on Days 191, 385 and 546

For the humoral immune response in terms of HI antibodies against any drift strain from A/chicken/Hong Kong/G9/1997 (H9N2) antigen, or against any other H9 subtype antigen, the following aggregate variables were calculated§:

‒ GMTs and seropositivity rate on Days 0, 7, 21, 28, 42, 182, 191, 385 and 546 ‒ SCR on Days 21, 42, 182, 191, 385 and 546 ‒ SPR on Days 0, 21, 42, 182, 191, 385 and 546 ‒ MGI on Day 21, 42, 182, 191, 385 and 546 ‒ B-SCR and BF on Days 191, 385 and 546

For the humoral immune response in terms of microneutralizing (MN) antibodies against A/chicken/Hong Kong/G9/1997 (H9N2) and against any drift strain (or other H9 subtype)§, the following parameters were calculated for a sub-cohort of subjects:

‒ GMTs and seropositivity rate on Days 0, 21, 42, 182, 191, 385§ and 546§ ‒ Vaccine response rate (VRR)*** on Days 21, 42, 182, 191, 385§ and 546§ ‒ Booster-VRR (B-VRR) on Days 191, 385§ and 546§

Safety:

Solicited local and general symptoms ‒ Occurrence of each solicited local symptom during a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after

any vaccination.

‒ Occurrence of each solicited general symptom during a 7-day follow-up period (i.e., day of vaccination and 6 subsequent days) after any vaccination.

Unsolicited adverse events ‒ Occurrence and relationship to vaccination of unsolicited adverse events within 21 days (Day 0 to Day 20, Day 21 to Day 41, Day

182 to Day 202) after any vaccination. ‒ Occurrence and relationship to vaccination of adverse events with medically attended visits (MAEs) during the entire study period. ‒ Occurrence and relationship to vaccination of adverse events of special interest (AESIs), potential immune-mediated diseases

(pIMDs), serious adverse events (SAEs) and adverse pregnancy outcome during the entire study period.

Clinical safety laboratory ‒ Number and percentages of subjects with clinical safety laboratory abnormalities on Days 0, 7, 21, 28, 42, 182, 191and 385.

*B-SCR was defined as the proportion of subjects that had either a pre-booster vaccination reciprocal HI titer < 10 and a post-booster vaccination reciprocal titer ≥ 40, or a pre-booster vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post-booster vaccination reciprocal titer against the vaccine virus. **BF was defined as the fold increase in H9N2 HI antibody GMTs between the pre- (Day 182) and post-booster vaccination time-points. ***VRR was defined as the incidence rate of vaccinees with at least a 4-fold increase in post vaccination reciprocal titer relative to Day 0 (before vaccination).Titers less than the cut-off titer were considered to be one-half the cut-off titer. §The analysis was not done.

Statistical Methods: Analyses were performed on the Total Vaccinated cohort, and the According-to-Protocol (ATP) cohort for immunogenicity at Days 21 and 42. The data of the final analysis conducted at the end of the study and encompassing all data were presented for the Adapted ATP cohort for immunogenicity.

The Total Vaccinated cohort included all subjects with at least one vaccine or placebo administration documented. ‒ The ATP cohort for immunogenicity at Days 21 and 42 included all evaluable subjects (i.e., those meeting all eligibility criteria,

complying with the procedures defined in the protocol, with no elimination criteria during the analysis interval) who received the study vaccine according to their treatment assignment, for whom no immunoglobulins and/or any blood products were administered between Days 0-21 and Days 0-42, respectively and for whom the assay results for antibodies against the vaccine-homologous H9N2 HA antigen for the blood sample(s) taken during the specified analysis interval were available.

‒ The Adapted ATP cohort for immunogenicity included data from the ATP cohorts for immunogenicity at Days 21, 42, 182, 191, 385 and 546.

Analysis of Immunogenicity The analyses were performed on the ATP cohorts for immunogenicity at Days 21 and 42. The data of the final analysis conducted at the end of the study and encompassing all data were presented for the Adapted ATP cohort for immunogenicity. For the humoral response in terms of HI antibodies against A/chicken/Hong Kong/G9/1997 (H9N2) antigen, GMTs and seropositivity rates, SPRs on Days 0, 7, 21, 28, 42, 182, 191, 385 and 546 and SCRs, MGIs on Days 7, 21, 28, 42, 182, 191, 385 and 546 were tabulated for each vaccine group and for age strata (18-40 years, 41-64 years) with 95% CI. For the humoral response in terms of MN antibodies against A/chicken/Hong Kong/G9/1997 (H9N2) antigen, GMTs and seropositivity rates on Days 0, 21, 42, 182 and 191 and VRRs on Days 21, 42, 182 and 191 were tabulated for a sub-cohort of immune subset with 95% CI. Analysis of Safety The analysis was performed on the Total Vaccinated cohort. The percentage of subjects reporting each individual solicited local and general symptom during the 7 days (Day 0 – Day 6) follow-up period for each dose and across doses were tabulated with exact 95% CI. The same tabulation was performed for grade 3 solicited AEs and for solicited general AEs assessed by the investigator as causally related to vaccination. The occurrences of clinically relevant abnormalities in biochemical and haematological parameters for all groups were assessed at Days 0, 7, 21, 28, 42, 182, 191 and 385. The percentages of subjects with at least one report of an unsolicited AE classified by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term within 21 days after each vaccination were tabulated. The same tabulation was done for AEs assessed by the investigator as related to vaccination. The percentages of subjects reporting SAEs, MAEs, AESIs and pIMDs during the entire study period (Day 0 – Day 546) and that of SAEs related to vaccination were summarized and classified according to MedDRA Preferred Term. The percentages of subjects reporting pregnancy outcomes and related pregnancy outcomes during the entire study period (Day 0 – Day 546) were also tabulated.

Study Population: Healthy adults from 18 to 64 years of age at time of first study vaccination, with a body weight of at least 110 lbs (49.9 kg) and access to a consistent means of telephone contact were included in this study. Subjects with presence or evidence of substance abuse or subjects diagnosed with cancer, or treatment for cancer within three years were excluded from the study.

Number of subjects Q-PAN-1A Group 1

Q-PAN-1B Group 1

Q-PAN-1C Group 1

Q-PAN-1D Group 1

Q-PAN-2 Group 1

Planned, N 30 30 30 30 30

Randomised, N (Total Vaccinated cohort) 31 30 30 30 30

Completed up to Day 42, n (%) 31 (100) 30 (100) 30 (100) 29 (96.7) 30 (100) Completed up to Day 182, n (%) 30 (96.8) 29 (96.7) 29 (96.7) 30 (100) 29 (96.7)

Completed up to Day 385, n (%) 27 (87.1)) 29 (96.7) 23 (76.7) 25 (83.3) 28 (93.3)

Completed up to Day 546, n (%) 26 (83.9) 29 (96.7) 23 (76.7) 24 (80.0) 27 (90.0)

Total Number Subjects Withdrawn, n (%) 5 (16.1) 1 (3.3) 7 (23.3) 6 (20.0) 3 (10.0) Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Withdrawn due to Lack of Efficacy, n (%) Not Applicable Not Applicable Not Applicable Not Applicable Not Applicable

Withdrawn for other reasons, n (%) 5 (16.1) 1 (3.3) 7 (23.3) 6 (20.0) 3 (10.0) Demographics Q-PAN-1A

Group 1 Q-PAN-1B Group

1 Q-PAN-1C Group 1

Q-PAN-1D Group 1

Q-PAN-2 Group 1

N (Total Vaccinated cohort) 31 30 30 30 30 Females: Males 15:16 18:12 13:17 18:12 21:9

Mean Age, years (SD) 41.5 (12.2) 43.1 (12.0) 42.7 (12.9) 40.7 (12.8) 42.3 (13.6)

Median Age, years (minimum, maximum) 42 (19, 63) 45 (20, 62) 46 (18, 61) 43 (20, 60) 45 (18, 63)

White - Caucasian / European Heritage, n (%) 24 (77.4) 23 (76.7) 23 (76.7) 25 (83.3) 24 (80.0) African Heritage / African American, n (%) 7 (22.6) 6 (20.0) 6 (20.0) 5 (16.7) 5 (16.7)

Number of subjects Q-PAN-1A Group 2

Q-PAN-1B Group 2

Q-PAN-1C Group 2

Q-PAN-1D Group 2

Q-PAN-2 Group 2

Placebo Group

Planned, N 30 30 30 30 30 120

Randomised, N (Total Vaccinated cohort) 30 30 30 31 30 118 Completed up to Day 42, n (%) 29 (96.7) 30 (100) 29 (96.7) 30 (96.8) 28 (93.3) 116 (98.3)

Completed up to Day 182, n (%) 25 (83.3)) 29 (96.7) 27 (90) 27 (87.1) 27 (90) 115 (97.5)

Completed up to Day 385, n (%) 25 (83.3) 25 (83.3) 27 (90) 24 (77.4) 26 (86.7) 111 (94.1)

Completed up to Day 546, n (%) 24 (80.0) 25 (83.3) 27 (90.0) 24 (77.4) 26 (86.7) 110 (93.2) Total Number Subjects Withdrawn, n (%) 6 (20.0) 5 (16.7) 3 (10.0) 7 (22.6) 4 (13.3) 8 (6.7)

Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.8)

Withdrawn due to Lack of Efficacy, n (%) Not Applicable

Not Applicable

Not Applicable

Not Applicable

Not Applicable

Not Applicable

Withdrawn for other reasons, n (%) 6 (20.0) 5 (16.7) 3 (10.0) 7 (22.6) 4 (13.3) 7 (5.9)

Demographics Q-PAN-1A Group 2

Q-PAN-1B Group 2

Q-PAN-1C Group 2

Q-PAN-1D Group 2

Q-PAN-2 Group 2

Placebo Group

N (Total Vaccinated cohort) 30 30 30 31 30 118

Females:Males 15:15 17:13 16:14 13:18 12:18 71:47 Mean Age, years (SD) 43.9 (11.0) 41.6 (12.1) 41.5 (13.2) 43.2 (11.6) 41.2 (13.1) 42.4 (12.8)

Median Age, years (minimum, maximum) 48 (22, 63) 44 (18, 61) 43 (19, 64) 43 (22, 62) 42 (22, 64) 44 (18, 64)

White - Caucasian / European Heritage, n (%) 24 (80.0) 25 (83.3) 23 (76.7) 25 (80.6) 21 (70.0) 91 (77.1)

African Heritage / African American, n (%) 6 (20.0) 4 (13.3) 7 (23.3) 5 (16.1) 6 (20.0) 23 (19.5)

Primary Efficacy Result(s): Flu A/Chicken/Hong Kong/G9/97 (H9N2) HI antibody parameters (Seropositivity rate, SPR, GMT, SCR, MGI) (Adapted ATP cohort for immunogenicity)

N ≥1:10 SPR$ GMT N’ SCR*$ MGI**$

95%CI 95%CI 95%CI 95%CI 95%CI

Group Timing n’’ % LL UL n %┼ LL┼ UL Value LL UL n’ %& LL& UL Value# LL UL

Q-PAN-1A Group 2

PRE 28 10 35.7 18.6 55.9 7 25.0 10.7 44.9 11.7 6.8 19.9 - - PI(D7) 28 25 89.3 71.8 97.7 20 71.4 51.3 86.8 73.4 39.0 138.1 28 15 53.6 33.9 72.5 6.3 3.8 10.4

PI(D21)$ 28 28 100 87.7 100 28 100 87.7 100 386.8 244.0 613.3 28 27 96.4 81.7 99.9 33.2 20.0 55.2 PII(D28) 24 24 100 85.8 100 24 100 85.8 100 877.2 534.2 1440.5 24 23 95.8 78.9 99.9 73.4 38.2 141.0

PII(D42)$ 24 24 100 85.8 100 24 100 85.8 100 1555.9 1019.2 2375.2 24 23 95.8 78.9 99.9 130.2 71.0 238.8

PII(D182) 23 23 100 85.2 100 23 100 85.2 100 252.3 158.4 401.8 23 21 91.3 72.0 98.9 20.9 11.6 37.9 PIII(D191) 23 23 100 85.2 100 23 100 85.2 100 1226.5 932.4 1613.3 23 15 65.2 42.7 83.6 4.9 3.4 7.0

PIII(D385) 21 21 100 83.9 100 21 100 83.9 100 458.1 299.7 700.2 21 8 38.1 18.1 61.6 2.1 1.3 3.2

PIII(D546) 22 22 100 84.6 100 22 100 84.6 100 561.4 341.3 923.2 21 9 42.9 21.8 66.0 2.7 1.9 4.0 Q-PAN-1A Group 1

PRE 31 9 29.0 14.2 48.0 6 19.4 7.5 37.5 9.6 6.3 14.7 - - PI(D7) 31 28 90.3 74.2 98.0 25 80.6 62.5 92.5 85.5 50.9 143.7 31 22 71.0 52.0 85.8 8.9 5.5 14.3

PI(D21)$ 31 31 100 88.8 100 31 100 88.8 100 408.4 284.4 586.3 31 30 96.8 83.3 99.9 42.5 29.9 60.4

PII(D28) 28 28 100 87.7 100 28 100 87.7 100 693.0 483.8 992.7 28 27 96.4 81.7 99.9 68.9 43.7 108.6

PII(D42)$ 29 29 100 88.1 100 29 100 88.1 100 1085.0 735.2 1601.4 29 29 100 88.1 100 107.9 66.5 175.2 PII(D182) 30 30 100 88.4 100 30 100 88.4 100 274.9 195.4 386.6 30 29 96.7 82.8 99.9 28.0 18.8 41.7

PIII(D191) 27 27 100 87.2 100 26 96.3 81.0 99.9 263.0 178.9 386.7 - - PIII(D385) 26 26 100 86.8 100 24 92.3 74.9 99.1 125.3 86.3 181.9 - - PIII(D546) 25 25 100 86.3 100 25 100 86.3 100 187.0 123.2 284.0 - -

Q-PAN-1B Group 2

PRE 30 7 23.3 9.9 42.3 4 13.3 3.8 30.7 8.7 5.7 13.3 - - PI(D7) 30 24 80.0 61.4 92.3 20 66.7 47.2 82.7 40.1 23.8 67.6 30 15 50.0 31.3 68.7 4.6 2.9 7.2 PI(D21)$ 30 30 100 88.4 100 29 96.7 82.8 99.9 285.3 178.1 457.2 30 29 96.7 82.8 99.9 32.8 20.6 52.2

PII(D28) 29 29 100 88.1 100 29 100 88.1 100 510.6 328.4 793.9 29 29 100 88.1 100 64.9 40.1 104.9

PII(D42)$ 29 29 100 88.1 100 29 100 88.1 100 861.2 585.9 1265.9 29 29 100 88.1 100 109.4 69.9 171.2 PII(D182) 29 29 100 88.1 100 29 100 88.1 100 166.2 110.2 250.8 29 29 100 88.1 100 18.7 13.5 25.9

PIII(D191) 28 28 100 87.7 100 28 100 87.7 100 778.7 521.9 1161.7 28 17 60.7 40.6 78.5 4.7 3.3 6.8

PIII(D385) 25 25 100 86.3 100 25 100 86.3 100 266.1 176.4 401.3 25 8 32.0 14.9 53.5 1.9 1.4 2.6

PIII(D546) 25 25 100 86.3 100 25 100 86.3 100 299.1 189.8 471.3 25 7 28.0 12.1 49.4 2.2 1.6 2.9 Q-PAN-1B Group 1

PRE 29 13 44.8 26.4 64.3 8 27.6 12.7 47.2 14.2 8.5 23.6 - - PI(D7) 29 23 79.3 60.3 92.0 20 69.0 49.2 84.7 45.8 27.0 77.9 29 8 27.6 12.7 47.2 3.2 2.0 5.1

PI(D21)$ 29 27 93.1 77.2 99.2 27 93.1 77.2 99.2 209.4 128.2 342.1 29 24 82.8 64.2 94.2 14.7 8.4 26.0

PII(D28) 26 26 100 86.8 100 26 100 86.8 100 467.1 323.2 674.9 26 25 96.2 80.4 99.9 35.7 19.9 64.0 PII(D42)$ 26 26 100 86.8 100 26 100 86.8 100 892.4 616.1 1292.7 26 25 96.2 80.4 99.9 68.2 36.4 127.6

PII(D182) 26 26 100 86.8 100 25 96.2 80.4 99.9 176.0 116.8 265.2 26 21 80.8 60.6 93.4 12.2 7.3 20.6

PIII(D191) 24 24 100 85.8 100 24 100 85.8 100 167.6 106.9 262.8 - - PIII(D385) 22 21 95.5 77.2 99.9 17 77.3 54.6 92.2 70.0 41.1 119.3 - - PIII(D546) 25 22 88.0 68.8 97.5 20 80.0 59.3 93.2 83.5 46.5 149.9 - -

Q-PAN-1C Group 2

PRE 28 9 32.1 15.9 52.4 5 17.9 6.1 36.9 10.1 6.3 16.3 - - PI(D7) 28 26 92.9 76.5 99.1 21 75.0 55.1 89.3 81.8 49.2 135.9 28 16 57.1 37.2 75.5 8.1 4.6 14.2

PI(D21)$ 28 28 100 87.7 100 28 100 87.7 100 375.5 248.5 567.4 28 26 92.9 76.5 99.1 37.0 21.4 64.2

PII(D28) 26 26 100 86.8 100 26 100 86.8 100 945.0 619.2 1442.2 26 25 96.2 80.4 99.9 88.3 46.4 168.1 PII(D42)$ 26 26 100 86.8 100 26 100 86.8 100 1202.6 842.2 1717.2 26 25 96.2 80.4 99.9 112.4 61.3 206.1

PII(D182) 26 26 100 86.8 100 26 100 86.8 100 282.5 183.4 435.3 25 24 96.0 79.6 99.9 28.9 16.9 49.5

PIII(D191) 25 25 100 86.3 100 25 100 86.3 100 1113.1 794.6 1559.2 25 12 48.0 27.8 68.7 4.0 2.6 5.9

PIII(D385) 25 25 100 86.3 100 25 100 86.3 100 425.2 312.2 579.1 25 4 16.0 4.5 36.1 1.5 1.0 2.0 PIII(D546) 25 25 100 86.3 100 25 100 86.3 100 477.9 345.4 661.1 25 6 24.0 9.4 45.1 1.6 1.2 2.2

Q-PAN-1C Group 1

PRE 29 10 34.5 17.9 54.3 3 10.3 2.2 27.4 10.4 6.3 16.9 - - PI(D7) 29 28 96.6 82.2 99.9 24 82.8 64.2 94.2 116.4 65.2 208.0 29 22 75.9 56.5 89.7 11.2 6.6 19.0

PI(D21)$ 28 28 100 87.7 100 28 100 87.7 100 527.4 337.7 823.7 28 27 96.4 81.7 99.9 52.1 34.4 78.9 PII(D28) 29 29 100 88.1 100 29 100 88.1 100 948.1 649.5 1384.1 29 29 100 88.1 100 91.5 60.0 139.7

PII(D42)$ 29 29 100 88.1 100 29 100 88.1 100 1410.5 1052.3 1890.7 29 29 100 88.1 100 136.2 89.1 208.1

PII(D182) 27 27 100 87.2 100 27 100 87.2 100 336.5 221.1 512.4 27 27 100 87.2 100 41.0 27.9 60.2 PIII(D191) 25 25 100 86.3 100 25 100 86.3 100 339.7 214.5 537.9 - - PIII(D385) 21 21 100 83.9 100 20 95.2 76.2 99.9 133.6 84.2 212.1 - - PIII(D546) 20 20 100 83.2 100 20 100 83.2 100 174.5 109.0 279.2 - -

Q-PAN-1D Group 2

PRE 30 12 40.0 22.7 59.4 7 23.3 9.9 42.3 11.0 7.2 16.7 - - PI(D7) 30 27 90.0 73.5 97.9 24 80.0 61.4 92.3 71.6 43.0 119.4 30 18 60.0 40.6 77.3 6.5 3.9 10.8

PI(D21)$ 30 30 100 88.4 100 30 100 88.4 100 288.3 188.5 440.9 30 28 93.3 77.9 99.2 26.2 15.3 44.8 PII(D28) 29 29 100 88.1 100 29 100 88.1 100 572.3 378.2 865.9 29 28 96.6 82.2 99.9 51.8 28.1 95.6

PII(D42)$ 29 29 100 88.1 100 29 100 88.1 100 924.1 624.3 1368.0 29 28 96.6 82.2 99.9 83.7 45.3 154.9

PII(D182) 26 26 100 86.8 100 25 96.2 80.4 99.9 253.8 167.9 383.8 26 24 92.3 74.9 99.1 21.0 12.3 35.9

PIII(D191) 25 25 100 86.3 100 25 100 86.3 100 815.8 578.5 1150.4 25 8 32.0 14.9 53.5 3.0 2.2 4.1 PIII(D385) 23 23 100 85.2 100 23 100 85.2 100 343.8 235.9 501.2 23 2 8.7 1.1 28.0 1.2 0.8 1.7

PIII(D546) 23 23 100 85.2 100 23 100 85.2 100 396.9 250.7 628.1 23 2 8.7 1.1 28.0 1.4 1.0 1.9

Q-PAN-1D Group 1

PRE 29 10 34.5 17.9 54.3 6 20.7 8.0 39.7 10.8 6.7 17.3 - - PI(D7) 29 25 86.2 68.3 96.1 21 72.4 52.8 87.3 71.8 39.9 129.1 29 15 51.7 32.5 70.6 6.7 4.0 11.3 PI(D21)$ 29 28 96.6 82.2 99.9 28 96.6 82.2 99.9 335.3 205.9 546.1 29 27 93.1 77.2 99.2 31.2 18.5 52.5

PII(D28) 29 29 100 88.1 100 29 100 88.1 100 641.7 427.4 963.3 29 28 96.6 82.2 99.9 59.7 36.4 97.8

PII(D42)$ 29 29 100 88.1 100 29 100 88.1 100 1038.3 714.0 1509.9 29 29 100 88.1 100 96.5 57.5 162.2 PII(D182) 30 30 100 88.4 100 28 93.3 77.9 99.2 259.5 165.4 407.2 30 26 86.7 69.3 96.2 24.8 15.0 40.9

PIII(D191) 25 25 100 86.3 100 24 96.0 79.6 99.9 287.9 176.3 470.3 - - PIII(D385) 21 21 100 83.9 100 20 95.2 76.2 99.9 123.4 80.1 190.2 - - PIII(D546) 21 21 100 83.9 100 21 100 83.9 100 186.4 119.6 290.4 - -

Q-PAN-2 Group 2

PRE 25 8 32.0 14.9 53.5 4 16.0 4.5 36.1 9.0 6.1 13.2 - - PI(D7) 25 22 88.0 68.8 97.5 16 64.0 42.5 82.0 62.6 31.2 125.6 25 14 56.0 34.9 75.6 7.0 3.8 12.6 PI(D21) 25 24 96.0 79.6 99.9 23 92.0 74.0 99.0 203.4 105.9 390.4 25 22 88.0 68.8 97.5 22.6 12.8 40.0

PII(D28) 24 23 95.8 78.9 99.9 23 95.8 78.9 99.9 220.4 119.4 406.6 24 22 91.7 73.0 99.0 26.7 14.2 50.1

PII(D42) 24 24 100 85.8 100 24 100 85.8 100 272.4 168.4 440.8 24 24 100 85.8 100 33.0 20.7 52.8

PII(D182) 25 23 92.0 74.0 99.0 19 76.0 54.9 90.6 93.5 49.4 177.1 23 18 78.3 56.3 92.5 14.3 8.3 24.6 PIII(D191) 24 24 100 85.8 100 24 100 85.8 100 310.5 191.6 503.1 23 9 39.1 19.7 61.5 3.4 2.0 5.8

PIII(D385) 20 20 100 83.2 100 17 85.0 62.1 96.8 90.3 55.8 146.1 20 2 10.0 1.2 31.7 0.8 0.5 1.3

PIII(D546) 23 23 100 85.2 100 20 87.0 66.4 97.2 96.5 61.3 152.0 22 3 13.6 2.9 34.9 1.0 0.7 1.6 Q-PAN-2 Group 1

PRE 28 10 35.7 18.6 55.9 8 28.6 13.2 48.7 10.4 6.8 15.9 - - PI(D7) 28 22 78.6 59.0 91.7 20 71.4 51.3 86.8 49.1 27.6 87.6 28 15 53.6 33.9 72.5 4.7 2.8 7.9

PI(D21) 28 27 96.4 81.7 99.9 27 96.4 81.7 99.9 171.4 103.1 285.2 28 24 85.7 67.3 96.0 16.4 9.7 27.7

PII(D28) 27 26 96.3 81.0 99.9 26 96.3 81.0 99.9 229.8 132.8 397.8 27 24 88.9 70.8 97.6 21.4 12.1 38.0 PII(D42) 27 27 100 87.2 100 27 100 87.2 100 299.7 187.0 480.3 27 25 92.6 75.7 99.1 28.0 16.4 47.5

PII(D182) 26 25 96.2 80.4 99.9 23 88.5 69.8 97.6 127.8 75.2 217.1 26 20 76.9 56.4 91.0 11.6 6.4 20.9

PIII(D191) 24 23 95.8 78.9 99.9 20 83.3 62.6 95.3 124.8 69.2 225.2 - -

PIII(D385) 23 21 91.3 72.0 98.9 18 78.3 56.3 92.5 57.3 32.6 100.7 - - PIII(D546) 23 22 95.7 78.1 99.9 18 78.3 56.3 92.5 69.4 39.7 121.4 - -

Placebo PRE 98 30 30.6 21.7 40.7 16 16.3 9.6 25.2 9.3 7.6 11.4 - - PI(D7) 98 32 32.7 23.5 42.9 20 20.4 12.9 29.7 9.9 8.0 12.3 98 1 1.0 0.0 5.6 1.1 1.0 1.1 PI(D21) 98 32 32.7 23.5 42.9 19 19.4 12.1 28.6 10.3 8.2 13.1 98 3 3.1 0.6 8.7 1.1 1.0 1.2

PII(D28) 95 31 32.6 23.4 43.0 20 21.1 13.4 30.6 10.0 8.0 12.5 95 1 1.1 0.0 5.7 1.0 0.9 1.2

PII(D42) 95 34 35.8 26.2 46.3 24 25.3 16.9 35.2 11.0 8.7 13.9 95 3 3.2 0.7 9.0 1.1 1.0 1.3

PII(D182) 102 40 39.2 29.7 49.4 18 17.6 10.8 26.4 10.1 8.3 12.2 93 3 3.2 0.7 9.1 1.1 0.9 1.2 PIII(D191) 99 38 38.4 28.8 48.7 16 16.2 9.5 24.9 9.9 8.1 12.0 99 0 0.0 0.0 3.7 1.0 0.9 1.0

PIII(D385) 92 29 31.5 22.2 42.0 10 10.9 5.3 19.1 8.5 7.1 10.2 91 1 1.1 0.0 6.0 0.8 0.7 0.9

PIII(D546) 88 41 46.6 35.9 57.5 19 21.6 13.5 31.6 12.2 9.7 15.4 87 3 3.4 0.7 9.7 1.2 1.0 1.4

Seroprotection rate (SPR) = Subjects with antibody titers ≥ 1:40 SCR* =SCR for Day 7, 21, 28, 42 and 182, defined as: For initially seronegative subjects, antibody titer ≥ 1:40 at post-vaccination For initially seropositive subjects, antibody titer at post-vaccination ≥ 4 fold the pre-vaccination antibody titer ┼Criteria for SPR evaluation: According to CHMP guidelines, target = point estimate of SPR > 70% According to CBER guidelines target = LL of 95 % CI for SPR ≥ 70% SCR* =Booster SCR at Day 191, 385 and 546, defined as: For initially seronegative subjects at Day 182, antibody titer ≥ 1:40 at post booster-vaccination For initially seropositive subjects at Day 182, antibody titer at post booster-vaccination ≥ 4 fold the pre-booster-vaccination antibody titer &Criteria for SCR evaluation: According to CHMP guidelines, target = point estimate of SCR > 40% According to CBER guidelines target = LL of 95 % CI for SCR ≥ 40% GMT=geometric mean antibody titer calculated on all subjects MGI** = geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer MGI** = geometric mean (Booster Factor) of the within-subject ratios of the post-booster vaccination reciprocal HI titer to the pre booster-vaccination reciprocal HI titer #Criteria for MGI evaluation: According to CHMP guidelines, target = MGI > 2.5 N =Number of subjects with results available (for seropositivity rates, SPR and GMT computation) N’=Number of subjects with both pre and post results available (for SCR*, MGI** computation) n’’/%= number/percentage of subjects with titer equal to or above specified value n/% = Number/percentage of seroprotected subjects n’/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval: LL = Lower Limit UL = Upper Limit PRE = Pre-vaccination 1 at Day 0 PI(D7) = Post-vaccination 1 at Day 7 PI(D21) = Post-vaccination 1 at Day 21 PII(D28) = Post-vaccination 2 at Day 28 PII(D42) = Post-vaccination 2 at Day 42 PII(D182) = Pre Booster-vaccination at Day 182 PIII(D191) = Post Booster-vaccination at Day 191 PIII(D385) = Post Booster-vaccination at Day 385 PIII(D546) = Post Booster-vaccination at Day 546 $Primary Outcome variable

Secondary Outcome Variable(s): Flu A/Chicken/Hong Kong/G9/97 (H9N2) HI antibody parameters (Seropositivity rate, SPR, GMT, SCR, MGI) by age strata (Adapted ATP cohort for immunogenicity)

N ≥1:10 SPR GMT N’ SCR* MGI**

95%CI 95%CI 95%CI 95%CI 95%CI

Group Sub-group

Timing n’’ % LL UL n % LL UL Value LL UL n’ % LL UL Value LL UL

Q-PAN-1A Group 2

18-40Y

PRE 11 3 27.3 6.0 61.0 2 18.2 2.3 51.8 12.2 3.5 42.3 - - PI(D7) 11 11 100 71.5 100 7 63.6 30.8 89.1 88.1 31.0 250.4 11 5 45.5 16.7 76.6 7.2 3.1 16.7

PI(D21) 11 11 100 71.5 100 11 100 71.5 100 435.9 191.4 992.9 11 10 90.9 58.7 99.8 35.7 12.6 101.6 PII(D28) 10 10 100 69.2 100 10 100 69.2 100 1102.3 450.2 2699.1 10 9 90.0 55.5 99.7 82.6 21.6 315.7

PII(D42) 10 10 100 69.2 100 10 100 69.2 100 1735.0 689.8 4363.8 10 9 90.0 55.5 99.7 129.9 31.1 543.8

PII(D182) 11 11 100 71.5 100 11 100 71.5 100 316.3 127.5 784.5 11 10 90.9 58.7 99.8 25.9 8.8 75.9

PIII(D191) 11 11 100 71.5 100 11 100 71.5 100 1486.7 959.1 2304.5 11 6 54.5 23.4 83.3 4.7 2.6 8.6 PIII(D385) 10 10 100 69.2 100 10 100 69.2 100 639.3 362.8 1126.4 10 5 50.0 18.7 81.3 2.5 1.4 4.5

PIII(D546) 10 10 100 69.2 100 10 100 69.2 100 888.4 446.6 1767.4 10 5 50.0 18.7 81.3 3.5 2.3 5.4

41-64Y

PRE 17 7 41.2 18.4 67.1 5 29.4 10.3 56.0 11.3 6.6 19.4 - - PI(D7) 17 14 82.4 56.6 96.2 13 76.5 50.1 93.2 65.2 27.0 157.4 17 10 58.8 32.9 81.6 5.8 2.9 11.5 PI(D21) 17 17 100 80.5 100 17 100 80.5 100 358.0 193.7 662.0 17 17 100 80.5 100 31.7 17.3 57.9

PII(D28) 14 14 100 76.8 100 14 100 76.8 100 745.1 387.0 1434.7 14 14 100 76.8 100 67.5 31.3 145.7

PII(D42) 14 14 100 76.8 100 14 100 76.8 100 1439.3 917.1 2258.8 14 14 100 76.8 100 130.4 75.9 224.0

PII(D182) 12 12 100 73.5 100 12 100 73.5 100 205.1 127.7 329.5 12 11 91.7 61.5 99.8 17.2 8.2 36.2 PIII(D191) 12 12 100 73.5 100 12 100 73.5 100 1028.1 707.6 1493.9 12 9 75.0 42.8 94.5 5.0 3.0 8.5

PIII(D385) 11 11 100 71.5 100 11 100 71.5 100 338.3 175.1 653.8 11 3 27.3 6.0 61.0 1.7 0.8 3.5

PIII(D546) 12 12 100 73.5 100 12 100 73.5 100 382.9 185.8 789.3 11 4 36.4 10.9 69.2 2.2 1.1 4.2 Q-PAN-1A Group 1

18-40Y

PRE 13 1 7.7 0.2 36.0 1 7.7 0.2 36.0 6.0 4.1 8.8 - - PI(D7) 13 11 84.6 54.6 98.1 10 76.9 46.2 95.0 69.3 28.2 170.0 13 10 76.9 46.2 95.0 11.6 5.1 26.5

PI(D21) 13 13 100 75.3 100 13 100 75.3 100 318.0 194.6 519.8 13 13 100 75.3 100 53.3 35.5 79.9

PII(D28) 11 11 100 71.5 100 11 100 71.5 100 669.5 363.9 1231.7 11 11 100 71.5 100 108.6 57.3 205.7 PII(D42) 11 11 100 71.5 100 11 100 71.5 100 1043.0 492.6 2208.3 11 11 100 71.5 100 169.2 75.4 379.7

PII(D182) 12 12 100 73.5 100 12 100 73.5 100 234.0 140.0 391.1 12 12 100 73.5 100 38.6 20.7 72.1

PIII(D191) 11 11 100 71.5 100 11 100 71.5 100 219.8 127.2 379.5 - - PIII(D385) 11 11 100 71.5 100 11 100 71.5 100 110.5 66.2 184.5 - - PIII(D546) 9 9 100 66.4 100 9 100 66.4 100 172.0 88.2 335.3 - -

41-64Y

PRE 18 8 44.4 21.5 69.2 5 27.8 9.7 53.5 13.6 7.0 26.4 - - PI(D7) 18 17 94.4 72.7 99.9 15 83.3 58.6 96.4 99.6 50.1 198.0 18 12 66.7 41.0 86.7 7.3 3.9 13.7

PI(D21) 18 18 100 81.5 100 18 100 81.5 100 489.2 285.9 837.0 18 17 94.4 72.7 99.9 36.1 20.7 62.7

PII(D28) 17 17 100 80.5 100 17 100 80.5 100 708.6 431.2 1164.7 17 16 94.1 71.3 99.9 51.3 27.2 96.9

PII(D42) 18 18 100 81.5 100 18 100 81.5 100 1111.5 677.7 1823.1 18 18 100 81.5 100 82.0 43.6 154.1 PII(D182) 18 18 100 81.5 100 18 100 81.5 100 306.1 187.5 499.5 18 17 94.4 72.7 99.9 22.6 13.1 38.9

PIII(D191) 16 16 100 79.4 100 15 93.8 69.8 99.8 297.7 167.5 528.9 - - PIII(D385) 15 15 100 78.2 100 13 86.7 59.5 98.3 137.3 77.1 244.5 - - PIII(D546) 16 16 100 79.4 100 16 100 79.4 100 196.1 108.6 354.0 - -

Q-PAN-1B Group 2

18-40Y

PRE 12 4 33.3 9.9 65.1 3 25.0 5.5 57.2 13.3 4.9 36.3 - - PI(D7) 12 10 83.3 51.6 97.9 9 75.0 42.8 94.5 59.8 23.1 155.2 12 6 50.0 21.1 78.9 4.5 2.1 9.4 PI(D21) 12 12 100 73.5 100 12 100 73.5 100 531.7 226.2 1249.7 12 12 100 73.5 100 39.8 14.7 107.9

PII(D28) 11 11 100 71.5 100 11 100 71.5 100 791.7 350.8 1786.8 11 11 100 71.5 100 74.3 27.7 199.4

PII(D42) 11 11 100 71.5 100 11 100 71.5 100 1178.7 549.9 2526.7 11 11 100 71.5 100 110.7 44.3 276.3 PII(D182) 11 11 100 71.5 100 11 100 71.5 100 247.8 106.3 577.8 11 11 100 71.5 100 17.0 9.1 31.6

PIII(D191) 11 11 100 71.5 100 11 100 71.5 100 1011.6 429.6 2381.8 11 7 63.6 30.8 89.1 4.1 2.1 7.8

PIII(D385) 10 10 100 69.2 100 10 100 69.2 100 372.9 163.7 849.3 10 4 40.0 12.2 73.8 2.0 1.1 3.4

PIII(D546) 10 10 100 69.2 100 10 100 69.2 100 414.8 181.1 950.2 10 3 30.0 6.7 65.2 2.2 1.3 3.7 41-64Y

PRE 18 3 16.7 3.6 41.4 1 5.6 0.1 27.3 6.5 4.8 9.0 - - PI(D7) 18 14 77.8 52.4 93.6 11 61.1 35.7 82.7 30.7 16.1 58.6 18 9 50.0 26.0 74.0 4.7 2.5 8.8

PI(D21) 18 18 100 81.5 100 17 94.4 72.7 99.9 188.4 112.0 316.9 18 17 94.4 72.7 99.9 28.8 17.5 47.4

PII(D28) 18 18 100 81.5 100 18 100 81.5 100 390.6 229.0 666.2 18 18 100 81.5 100 59.7 33.5 106.2 PII(D42) 18 18 100 81.5 100 18 100 81.5 100 710.9 452.0 1118.0 18 18 100 81.5 100 108.6 63.1 186.9

PII(D182) 18 18 100 81.5 100 18 100 81.5 100 130.3 82.9 204.5 18 18 100 81.5 100 19.9 13.2 30.1

PIII(D191) 17 17 100 80.5 100 17 100 80.5 100 657.4 427.1 1011.8 17 10 58.8 32.9 81.6 5.2 3.2 8.3 PIII(D385) 15 15 100 78.2 100 15 100 78.2 100 212.5 133.2 339.1 15 4 26.7 7.8 55.1 1.9 1.3 2.8

PIII(D546) 15 15 100 78.2 100 15 100 78.2 100 240.5 134.9 428.8 15 4 26.7 7.8 55.1 2.1 1.4 3.2

Q-PAN-1B Group 1

18-40Y

PRE 12 4 33.3 9.9 65.1 1 8.3 0.2 38.5 8.8 5.0 15.5 - - PI(D7) 12 11 91.7 61.5 99.8 10 83.3 51.6 97.9 64.0 31.8 129.0 12 7 58.3 27.7 84.8 7.3 3.2 16.8 PI(D21) 12 11 91.7 61.5 99.8 11 91.7 61.5 99.8 253.3 101.1 634.4 12 11 91.7 61.5 99.8 28.8 11.0 75.8

PII(D28) 12 12 100 73.5 100 12 100 73.5 100 685.9 425.7 1105.3 12 12 100 73.5 100 78.1 34.5 177.0

PII(D42) 12 12 100 73.5 100 12 100 73.5 100 1393.4 828.2 2344.1 12 12 100 73.5 100 158.6 63.1 398.5

PII(D182) 12 12 100 73.5 100 11 91.7 61.5 99.8 219.2 123.2 390.0 12 11 91.7 61.5 99.8 25.0 11.6 53.8 PIII(D191) 11 11 100 71.5 100 11 100 71.5 100 196.8 100.8 384.3 - -

PIII(D385) 9 9 100 66.4 100 7 77.8 40.0 97.2 77.5 29.8 201.8 - - PIII(D546) 10 9 90.0 55.5 99.7 9 90.0 55.5 99.7 124.0 45.5 337.7 - -

41-64Y

PRE 17 9 52.9 27.8 77.0 7 41.2 18.4 67.1 19.9 9.2 43.4 - - PI(D7) 17 12 70.6 44.0 89.7 10 58.8 32.9 81.6 36.2 16.3 80.7 17 1 5.9 0.1 28.7 1.8 1.2 2.7 PI(D21) 17 16 94.1 71.3 99.9 16 94.1 71.3 99.9 183.1 99.0 338.6 17 13 76.5 50.1 93.2 9.2 4.7 18.0

PII(D28) 14 14 100 76.8 100 14 100 76.8 100 336.0 196.2 575.2 14 13 92.9 66.1 99.8 18.2 8.8 37.6

PII(D42) 14 14 100 76.8 100 14 100 76.8 100 609.1 374.3 991.2 14 13 92.9 66.1 99.8 33.1 15.8 69.1

PII(D182) 14 14 100 76.8 100 14 100 76.8 100 145.8 77.4 274.7 14 10 71.4 41.9 91.6 6.6 3.6 12.1 PIII(D191) 13 13 100 75.3 100 13 100 75.3 100 146.3 73.4 291.6 - - PIII(D385) 13 12 92.3 64.0 99.8 10 76.9 46.2 95.0 65.2 31.2 136.2 - - PIII(D546) 15 13 86.7 59.5 98.3 11 73.3 44.9 92.2 64.2 29.4 140.2 - -

Q-PAN-1C Group 2

18-40Y

PRE 12 3 25.0 5.5 57.2 1 8.3 0.2 38.5 7.2 4.4 11.7 - - PI(D7) 12 11 91.7 61.5 99.8 9 75.0 42.8 94.5 89.1 37.6 211.1 12 8 66.7 34.9 90.1 12.4 4.6 33.4

PI(D21) 12 12 100 73.5 100 12 100 73.5 100 332.0 149.5 737.6 12 11 91.7 61.5 99.8 46.0 17.9 118.1 PII(D28) 11 11 100 71.5 100 11 100 71.5 100 919.5 422.1 2002.8 11 11 100 71.5 100 123.3 47.6 319.6

PII(D42) 11 11 100 71.5 100 11 100 71.5 100 1120.7 585.9 2143.5 11 11 100 71.5 100 150.3 63.2 357.5

PII(D182) 12 12 100 73.5 100 12 100 73.5 100 223.8 107.0 467.8 11 11 100 71.5 100 33.0 14.7 73.8 PIII(D191) 12 12 100 73.5 100 12 100 73.5 100 1302.3 730.2 2322.8 12 8 66.7 34.9 90.1 5.8 2.9 11.8

PIII(D385) 12 12 100 73.5 100 12 100 73.5 100 426.5 288.2 631.2 12 3 25.0 5.5 57.2 1.9 1.2 3.1

PIII(D546) 12 12 100 73.5 100 12 100 73.5 100 474.3 303.9 740.5 12 4 33.3 9.9 65.1 2.1 1.3 3.4

41-64Y

PRE 16 6 37.5 15.2 64.6 4 25.0 7.3 52.4 13.1 6.1 28.3 - - PI(D7) 16 15 93.8 69.8 99.8 12 75.0 47.6 92.7 76.7 38.0 154.6 16 8 50.0 24.7 75.3 5.9 2.9 11.9

PI(D21) 16 16 100 79.4 100 16 100 79.4 100 411.8 251.1 675.3 16 15 93.8 69.8 99.8 31.5 15.0 66.2

PII(D28) 15 15 100 78.2 100 15 100 78.2 100 964.2 554.8 1675.6 15 14 93.3 68.1 99.8 69.1 26.7 178.8

PII(D42) 15 15 100 78.2 100 15 100 78.2 100 1266.4 792.4 2023.7 15 14 93.3 68.1 99.8 90.8 36.4 226.5 PII(D182) 14 14 100 76.8 100 14 100 76.8 100 345.0 195.4 609.3 14 13 92.9 66.1 99.8 26.1 11.6 59.0

PIII(D191) 13 13 100 75.3 100 13 100 75.3 100 962.9 621.4 1492.3 13 4 30.8 9.1 61.4 2.8 1.8 4.2

PIII(D385) 13 13 100 75.3 100 13 100 75.3 100 424.0 249.3 720.9 13 1 7.7 0.2 36.0 1.1 0.7 1.8 PIII(D546) 13 13 100 75.3 100 13 100 75.3 100 481.2 281.6 822.2 13 2 15.4 1.9 45.4 1.3 0.8 2.0

Q-PAN-1C Group 1

18-40Y

PRE 11 1 9.1 0.2 41.3 0 0.0 0.0 28.5 5.5 4.4 6.9 - - PI(D7) 11 10 90.9 58.7 99.8 8 72.7 39.0 94.0 61.4 24.0 157.4 11 7 63.6 30.8 89.1 11.1 4.1 29.9

PI(D21) 11 11 100 71.5 100 11 100 71.5 100 396.3 170.5 920.7 11 11 100 71.5 100 71.7 37.0 139.0 PII(D28) 11 11 100 71.5 100 11 100 71.5 100 783.0 387.1 1583.7 11 11 100 71.5 100 141.7 82.6 243.0

PII(D42) 11 11 100 71.5 100 11 100 71.5 100 1179.2 659.7 2107.8 11 11 100 71.5 100 213.4 136.3 334.2

PII(D182) 11 11 100 71.5 100 11 100 71.5 100 318.3 148.0 684.6 11 11 100 71.5 100 57.6 30.4 109.1

PIII(D191) 11 11 100 71.5 100 11 100 71.5 100 310.5 146.9 656.3 - - PIII(D385) 10 10 100 69.2 100 9 90.0 55.5 99.7 110.9 44.5 276.5 - - PIII(D546) 8 8 100 63.1 100 8 100 63.1 100 180.5 64.8 502.7 - -

41-64Y

PRE 18 9 50.0 26.0 74.0 3 16.7 3.6 41.4 15.2 7.2 32.1 - - PI(D7) 18 18 100 81.5 100 16 88.9 65.3 98.6 172.1 81.5 363.2 18 15 83.3 58.6 96.4 11.3 5.7 22.4

PI(D21) 17 17 100 80.5 100 17 100 80.5 100 634.6 365.3 1102.4 17 16 94.1 71.3 99.9 42.4 24.1 74.6

PII(D28) 18 18 100 81.5 100 18 100 81.5 100 1065.7 657.3 1728.0 18 18 100 81.5 100 70.1 38.5 127.7 PII(D42) 18 18 100 81.5 100 18 100 81.5 100 1573.8 1105.6 2240.1 18 18 100 81.5 100 103.5 55.5 193.1

PII(D182) 16 16 100 79.4 100 16 100 79.4 100 349.7 200.7 609.4 16 16 100 79.4 100 32.4 19.6 53.7

PIII(D191) 14 14 100 76.8 100 14 100 76.8 100 364.5 187.6 708.2 - - PIII(D385) 11 11 100 71.5 100 11 100 71.5 100 158.3 97.2 257.9 - - PIII(D546) 12 12 100 73.5 100 12 100 73.5 100 170.6 97.1 299.6 - -

Q-PAN-1D Group 2

18-40Y

PRE 13 3 23.1 5.0 53.8 2 15.4 1.9 45.4 7.5 4.5 12.6 - - PI(D7) 13 10 76.9 46.2 95.0 8 61.5 31.6 86.1 32.5 14.3 74.1 13 7 53.8 25.1 80.8 4.3 2.3 8.1

PI(D21) 13 13 100 75.3 100 13 100 75.3 100 222.8 120.6 411.4 13 13 100 75.3 100 29.7 15.9 55.7

PII(D28) 12 12 100 73.5 100 12 100 73.5 100 597.9 354.9 1007.3 12 12 100 73.5 100 81.7 39.2 170.5 PII(D42) 12 12 100 73.5 100 12 100 73.5 100 1043.2 592.7 1835.9 12 12 100 73.5 100 142.6 59.3 343.1

PII(D182) 11 11 100 71.5 100 10 90.9 58.7 99.8 239.5 130.5 439.5 11 10 90.9 58.7 99.8 31.6 14.0 71.4

PIII(D191) 10 10 100 69.2 100 10 100 69.2 100 969.4 655.3 1434.1 10 3 30.0 6.7 65.2 3.3 2.0 5.6

PIII(D385) 8 8 100 63.1 100 8 100 63.1 100 574.6 364.4 905.9 8 1 12.5 0.3 52.7 1.6 0.9 3.0 PIII(D546) 8 8 100 63.1 100 8 100 63.1 100 785.9 458.8 1346.1 8 1 12.5 0.3 52.7 2.3 1.3 4.0

41-64Y

PRE 17 9 52.9 27.8 77.0 5 29.4 10.3 56.0 14.8 7.8 27.9 - - PI(D7) 17 17 100 80.5 100 16 94.1 71.3 99.9 131.1 76.2 225.3 17 11 64.7 38.3 85.8 8.9 4.1 19.3

PI(D21) 17 17 100 80.5 100 17 100 80.5 100 351.1 187.9 656.1 17 15 88.2 63.6 98.5 23.8 9.9 57.3 PII(D28) 17 17 100 80.5 100 17 100 80.5 100 554.9 289.1 1065.1 17 16 94.1 71.3 99.9 37.6 14.7 96.2

PII(D42) 17 17 100 80.5 100 17 100 80.5 100 848.4 472.3 1524.0 17 16 94.1 71.3 99.9 57.5 23.9 138.0

PII(D182) 15 15 100 78.2 100 15 100 78.2 100 264.9 141.5 496.0 15 14 93.3 68.1 99.8 15.5 7.3 33.1 PIII(D191) 15 15 100 78.2 100 15 100 78.2 100 727.1 422.6 1251.1 15 5 33.3 11.8 61.6 2.7 1.8 4.2

PIII(D385) 15 15 100 78.2 100 15 100 78.2 100 261.5 158.6 430.9 15 1 6.7 0.2 31.9 1.0 0.6 1.5

PIII(D546) 15 15 100 78.2 100 15 100 78.2 100 275.7 152.0 499.9 15 1 6.7 0.2 31.9 1.0 0.7 1.5

Q-PAN-1D Group 1

18-40Y

PRE 13 2 15.4 1.9 45.4 1 7.7 0.2 36.0 7.0 4.2 11.8 - - PI(D7) 13 11 84.6 54.6 98.1 9 69.2 38.6 90.9 63.9 26.5 153.9 13 8 61.5 31.6 86.1 9.1 3.7 22.5

PI(D21) 13 12 92.3 64.0 99.8 12 92.3 64.0 99.8 294.3 121.6 712.0 13 11 84.6 54.6 98.1 42.0 15.0 118.1

PII(D28) 13 13 100 75.3 100 13 100 75.3 100 669.4 387.5 1156.5 13 13 100 75.3 100 95.6 44.7 204.5

PII(D42) 13 13 100 75.3 100 13 100 75.3 100 1110.1 666.6 1848.7 13 13 100 75.3 100 158.5 74.4 337.4 PII(D182) 13 13 100 75.3 100 12 92.3 64.0 99.8 260.0 118.4 570.8 13 10 76.9 46.2 95.0 37.1 13.7 100.4

PIII(D191) 10 10 100 69.2 100 9 90.0 55.5 99.7 249.2 91.0 682.3 - - PIII(D385) 7 7 100 59.0 100 7 100 59.0 100 130.8 71.1 240.7 - - PIII(D546) 7 7 100 59.0 100 7 100 59.0 100 206.7 85.5 499.8 - -

41-64Y

PRE 16 8 50.0 24.7 75.3 5 31.3 11.0 58.7 15.2 7.1 32.8 - - PI(D7) 16 14 87.5 61.7 98.4 12 75.0 47.6 92.7 78.9 32.7 190.2 16 7 43.8 19.8 70.1 5.2 2.6 10.2 PI(D21) 16 16 100 79.4 100 16 100 79.4 100 372.8 201.6 689.5 16 16 100 79.4 100 24.5 14.2 42.0

PII(D28) 16 16 100 79.4 100 16 100 79.4 100 620.0 324.8 1183.4 16 15 93.8 69.8 99.8 40.7 21.0 78.7

PII(D42) 16 16 100 79.4 100 16 100 79.4 100 983.3 544.3 1776.7 16 16 100 79.4 100 64.5 31.4 132.7 PII(D182) 17 17 100 80.5 100 16 94.1 71.3 99.9 259.1 142.0 472.9 17 16 94.1 71.3 99.9 18.2 10.9 30.4

PIII(D191) 15 15 100 78.2 100 15 100 78.2 100 317.0 176.3 570.2 - - PIII(D385) 14 14 100 76.8 100 13 92.9 66.1 99.8 119.9 63.9 224.8 - - PIII(D546) 14 14 100 76.8 100 14 100 76.8 100 177.0 98.5 318.0 - -

Q-PAN-2 Group 2

18-40Y

PRE 9 1 11.1 0.3 48.2 0 0.0 0.0 33.6 6.2 3.8 10.2 - - PI(D7) 9 7 77.8 40.0 97.2 6 66.7 29.9 92.5 44.0 14.3 135.4 9 6 66.7 29.9 92.5 7.1 2.8 18.1 PI(D21) 9 8 88.9 51.8 99.7 8 88.9 51.8 99.7 115.8 33.7 398.0 9 8 88.9 51.8 99.7 18.7 6.0 57.9

PII(D28) 9 9 100 66.4 100 9 100 66.4 100 238.8 116.6 488.9 9 9 100 66.4 100 38.5 19.3 76.9

PII(D42) 9 9 100 66.4 100 9 100 66.4 100 206.6 104.1 410.1 9 9 100 66.4 100 33.3 17.8 62.3

PII(D182) 10 9 90.0 55.5 99.7 7 70.0 34.8 93.3 72.7 25.8 204.7 9 7 77.8 40.0 97.2 15.8 6.8 36.7 PIII(D191) 10 10 100 69.2 100 10 100 69.2 100 246.0 127.2 475.9 9 3 33.3 7.5 70.1 3.0 1.1 8.2

PIII(D385) 7 7 100 59.0 100 7 100 59.0 100 97.5 47.8 199.0 7 1 14.3 0.4 57.9 0.8 0.4 1.7

PIII(D546) 10 10 100 69.2 100 10 100 69.2 100 81.8 44.6 150.0 9 2 22.2 2.8 60.0 1.0 0.5 2.3 41-64Y

PRE 16 7 43.8 19.8 70.1 4 25.0 7.3 52.4 11.1 6.4 19.1 - - PI(D7) 16 15 93.8 69.8 99.8 10 62.5 35.4 84.8 76.3 29.0 200.9 16 8 50.0 24.7 75.3 6.9 2.9 16.2

PI(D21) 16 16 100 79.4 100 15 93.8 69.8 99.8 279.1 123.9 628.6 16 14 87.5 61.7 98.4 25.2 12.2 52.1

PII(D28) 15 14 93.3 68.1 99.8 14 93.3 68.1 99.8 210.0 81.1 543.9 15 13 86.7 59.5 98.3 21.4 8.2 56.4 PII(D42) 15 15 100 78.2 100 15 100 78.2 100 321.6 159.6 648.0 15 15 100 78.2 100 32.8 16.1 66.8

PII(D182) 15 14 93.3 68.1 99.8 12 80.0 51.9 95.7 110.6 44.7 274.0 14 11 78.6 49.2 95.3 13.4 6.1 29.8

PIII(D191) 14 14 100 76.8 100 14 100 76.8 100 366.7 174.6 770.0 14 6 42.9 17.7 71.1 3.8 1.9 7.5

PIII(D385) 13 13 100 75.3 100 10 76.9 46.2 95.0 86.6 42.7 175.8 13 1 7.7 0.2 36.0 0.8 0.4 1.5 PIII(D546) 13 13 100 75.3 100 10 76.9 46.2 95.0 109.7 53.1 226.6 13 1 7.7 0.2 36.0 1.0 0.6 1.8

Q-PAN-2 Group 1

18-40Y

PRE 12 3 25.0 5.5 57.2 2 16.7 2.1 48.4 8.1 4.3 15.3 - - PI(D7) 12 9 75.0 42.8 94.5 8 66.7 34.9 90.1 42.2 15.2 116.9 12 7 58.3 27.7 84.8 5.2 2.1 13.0

PI(D21) 12 11 91.7 61.5 99.8 11 91.7 61.5 99.8 134.6 59.7 303.7 12 10 83.3 51.6 97.9 16.6 7.0 39.4 PII(D28) 12 12 100 73.5 100 12 100 73.5 100 223.2 130.3 382.4 12 12 100 73.5 100 27.6 14.4 53.0

PII(D42) 12 12 100 73.5 100 12 100 73.5 100 276.5 148.9 513.5 12 12 100 73.5 100 34.2 16.4 71.2

PII(D182) 11 11 100 71.5 100 9 81.8 48.2 97.7 126.7 62.5 256.8 11 9 81.8 48.2 97.7 15.0 7.2 31.1 PIII(D191) 11 11 100 71.5 100 9 81.8 48.2 97.7 126.7 62.5 256.8 - - PIII(D385) 11 10 90.9 58.7 99.8 8 72.7 39.0 94.0 51.9 22.8 118.0 - - PIII(D546) 10 9 90.0 55.5 99.7 8 80.0 44.4 97.5 72.8 30.0 176.6 - -

41-64Y

PRE 16 7 43.8 19.8 70.1 6 37.5 15.2 64.6 12.6 6.8 23.3 - - PI(D7) 16 13 81.3 54.4 96.0 12 75.0 47.6 92.7 55.1 25.5 119.0 16 8 50.0 24.7 75.3 4.4 2.2 8.6

PI(D21) 16 16 100 79.4 100 16 100 79.4 100 205.6 100.3 421.5 16 14 87.5 61.7 98.4 16.3 7.8 34.1

PII(D28) 15 14 93.3 68.1 99.8 14 93.3 68.1 99.8 235.2 90.1 614.5 15 12 80.0 51.9 95.7 17.5 6.7 45.5 PII(D42) 15 15 100 78.2 100 15 100 78.2 100 319.7 149.5 683.4 15 13 86.7 59.5 98.3 23.8 10.4 54.5

PII(D182) 15 14 93.3 68.1 99.8 14 93.3 68.1 99.8 128.5 55.6 297.0 15 11 73.3 44.9 92.2 9.6 3.7 24.5

PIII(D191) 13 12 92.3 64.0 99.8 11 84.6 54.6 98.1 123.3 44.7 340.1 - - PIII(D385) 12 11 91.7 61.5 99.8 10 83.3 51.6 97.9 62.8 25.5 154.8 - - PIII(D546) 13 13 100 75.3 100 10 76.9 46.2 95.0 66.9 29.0 154.3 - -

Placebo 18-40Y

PRE 39 7 17.9 7.5 33.5 3 7.7 1.6 20.9 7.1 5.4 9.2 - - PI(D7) 39 9 23.1 11.1 39.3 5 12.8 4.3 27.4 7.8 5.9 10.4 39 1 2.6 0.1 13.5 1.1 1.0 1.3

PI(D21) 39 6 15.4 5.9 30.5 3 7.7 1.6 20.9 7.0 5.3 9.2 39 1 2.6 0.1 13.5 1.0 0.8 1.2

PII(D28) 37 6 16.2 6.2 32.0 3 8.1 1.7 21.9 6.9 5.3 9.0 37 0 0.0 0.0 9.5 1.0 0.8 1.1

PII(D42) 37 10 27.0 13.8 44.1 5 13.5 4.5 28.8 9.0 6.2 13.0 37 2 5.4 0.7 18.2 1.2 0.9 1.7 PII(D182) 40 13 32.5 18.6 49.1 4 10.0 2.8 23.7 8.1 6.2 10.5 36 1 2.8 0.1 14.5 1.1 0.8 1.4

PIII(D191) 39 13 33.3 19.1 50.2 4 10.3 2.9 24.2 8.2 6.2 10.7 39 0 0.0 0.0 9.0 1.0 1.0 1.0

PIII(D385) 35 5 14.3 4.8 30.3 1 2.9 0.1 14.9 6.3 5.1 7.8 35 0 0.0 0.0 10.0 0.8 0.6 1.0 PIII(D546) 33 8 24.2 11.1 42.3 2 6.1 0.7 20.2 7.7 5.7 10.6 33 0 0.0 0.0 10.6 1.0 0.8 1.2

41-64Y

PRE 59 23 39.0 26.5 52.6 13 22.0 12.3 34.7 11.1 8.3 14.9 - - PI(D7) 59 23 39.0 26.5 52.6 15 25.4 15.0 38.4 11.6 8.6 15.6 59 0 0.0 0.0 6.1 1.0 1.0 1.1

PI(D21) 59 26 44.1 31.2 57.6 16 27.1 16.4 40.3 13.4 9.7 18.6 59 2 3.4 0.4 11.7 1.2 1.0 1.4 PII(D28) 58 25 43.1 30.2 56.8 17 29.3 18.1 42.7 12.7 9.3 17.4 58 1 1.7 0.0 9.2 1.1 0.9 1.3

PII(D42) 58 24 41.4 28.6 55.1 19 32.8 21.0 46.3 12.5 9.2 17.1 58 1 1.7 0.0 9.2 1.1 1.0 1.2

PII(D182) 62 27 43.5 31.0 56.7 14 22.6 12.9 35.0 11.6 8.8 15.3 57 2 3.5 0.4 12.1 1.1 0.9 1.3

PIII(D191) 60 25 41.7 29.1 55.1 12 20.0 10.8 32.3 11.2 8.5 14.7 60 0 0.0 0.0 6.0 0.9 0.9 1.0 PIII(D385) 57 24 42.1 29.1 55.9 9 15.8 7.5 27.9 10.3 7.9 13.3 56 1 1.8 0.0 9.6 0.8 0.7 1.0

PIII(D546) 55 33 60.0 45.9 73.0 17 30.9 19.1 44.8 16.1 12.0 21.6 54 3 5.6 1.2 15.4 1.3 1.0 1.6

18-40Y = 18-40 years of age 41-64Y = 41-64 years of age Seroprotection rate (SPR) = Subjects with antibody titers ≥ 1:40 SCR* =SCR for Day 7, 21, 28, 42 and 182, defined as: For initially seronegative subjects, antibody titer ≥ 1:40 at post-vaccination For initially seropositive subjects, antibody titer at post-vaccination ≥ 4 fold the pre-vaccination antibody titer SCR* =Booster SCR at Day 191, 385 and 546, defined as: For initially seronegative subjects at Day 182, antibody titer ≥ 1:40 at post booster-vaccination For initially seropositive subjects at Day 182, antibody titer at post booster-vaccination ≥ 4 fold the pre-booster-vaccination antibody titer GMT=geometric mean antibody titer calculated on all subjects MGI** = geometric mean of the within-subject ratios of the post-vaccination reciprocal HI to the pre-vaccination reciprocal HI titer MGI** = geometric mean (Booster Factor) of the within-subject ratios of the post-booster vaccination reciprocal HI titer to the pre booster-vaccination reciprocal HI titer N =Number of subjects with results available (for seropositivity rates, SPR and GMT computation) N’=Number of subjects with both pre and post results available (for SCR*, MGI** computation) n’’/%= number/percentage of subjects with titer equal to or above specified value n/% = Number/percentage of seroprotected subjects n’/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval: LL = Lower Limit UL = Upper Limit PRE = Pre-vaccination 1 at Day 0 PI(D7) = Post-vaccination 1 at Day 7 PI(D21) = Post-vaccination 1 at Day 21 PII(D28) = Post-vaccination 2 at Day 28 PII(D42) = Post-vaccination 2 at Day 42 PII(D182) = Pre Booster-vaccination at Day 182 PIII(D191) = Post Booster-vaccination at Day 191 PIII(D385) = Post Booster-vaccination at Day 385 PIII(D546) = Post Booster-vaccination at Day 546

Secondary Outcome Variable(s): Flu A/Chicken/Hong Kong/G9/97 (H9N2) neutralizing antibody parameters (Seropositivity rates, GMT, Vaccine response) for pooled group at Day 0, Day 42 and Day 182 (Adapted ATP cohort for immunogenicity - Immune subset)

N ≥ 1:28 GMT N’ Vaccine response

95%CI 95%CI 95%CI

Antibody Group Timing n % LL UL Value LL UL n’ % LL UL

Flu A/chicken/Hong Kong/G9/1997 H9N2 MN

Q-PAN-1A PRE 27 24 88.9 70.8 97.6 57.9 43.3 77.5 - -

PII(D42) 25 25 100 86.3 100 862.4 546.4 1361.1 25 24 96.0 79.6 99.9

PII(D182) 25 25 100 86.3 100 234.5 173.1 317.7 25 14 56.0 34.9 75.6

Q-PAN-1B PRE 25 20 80.0 59.3 93.2 61.4 42.2 89.2 - - PII(D42) 23 23 100 85.2 100 495.3 356.2 688.9 23 15 65.2 42.7 83.6

PII(D182) 23 23 100 85.2 100 183.1 140.8 238.1 23 9 39.1 19.7 61.5

Q-PAN-1C PRE 26 23 88.5 69.8 97.6 49.3 35.5 68.5 - -

PII(D42) 25 25 100 86.3 100 596.4 394.8 900.9 25 22 88.0 68.8 97.5

PII(D182) 24 24 100 85.8 100 190.2 138.9 260.4 24 12 50.0 29.1 70.9

Q-PAN-1D PRE 25 20 80.0 59.3 93.2 53.4 37.6 75.9 - -

PII(D42) 25 25 100 86.3 100 641.7 414.0 994.5 25 17 68.0 46.5 85.1

PII(D182) 23 23 100 85.2 100 249.9 171.6 363.9 23 14 60.9 38.5 80.3

Q-PAN-2 PRE 24 19 79.2 57.8 92.9 50.3 35.3 71.6 - -

PII(D42) 23 23 100 85.2 100 172.5 126.6 235.0 23 11 47.8 26.8 69.4

PII(D182) 22 22 100 84.6 100 113.2 83.9 152.7 22 8 36.4 17.2 59.3 Placebo PRE 46 40 87.0 73.7 95.1 53.2 43.0 65.8 - -

PII(D42) 46 39 84.8 71.1 93.7 49.3 39.5 61.5 46 0 0.0 0.0 7.7

PII(D182) 45 43 95.6 84.9 99.5 66.0 53.6 81.3 45 2 4.4 0.5 15.1

Vaccine response defined as: For initially seronegative subjects, antibody titer ≥ 56 at post-vaccination For initially seropositive subjects, antibody titer at post-vaccination ≥ 4 fold the pre-vaccination antibody titer GMT=geometric mean antibody titer calculated on all subjects N = Number of subjects with results available (for GMT and seropositivity) N’= Number of subjects with both pre and post results available (for vaccine response) n/% = Number/percentage of subjects with titer equal to or above specified value n’/% = Number/percentage of responders 95% CI = 95% confidence interval: LL = Lower Limit UL = Upper Limit PRE = Pre-vaccination 1 at Day 0 PII(D42) = Post-vaccination 2 at Day 42 PII(D182) = Pre Booster-vaccination at Day 182

Secondary Outcome Variable(s): Flu A/Chicken/Hong Kong/G9/97 (H9N2) neutralizing antibody parameters (Seropositivity rates, GMT, Vaccine response) from Day 182 to Day 191 (Adapted ATP cohort for immunogenicity - Immune subset)

N ≥ 1:28 GMT N’ Booster Vaccine response

95%CI 95%CI 95%CI Antibody Group Timing n % LL UL Value LL UL n’ % LL UL

Flu A/chicken/Hong Kong/G9/1997 H9N2 MN

Q-PAN-1A Group 2 PII(D182) 11 11 100 71.5 100 226.1 157.6 324.5 - -

PIII(D191) 11 11 100 71.5 100 1493.0 859.1 2594.7 11 9 81.8 48.2 97.7

Q-PAN-1A Group 1 PII(D182) 14 14 100 76.8 100 241.3 145.3 401.0 - -

PIII(D191) 13 13 100 75.3 100 230.0 131.4 402.3 13 0 0.0 0.0 24.7

Q-PAN-1B Group 2 PII(D182) 13 13 100 75.3 100 147.5 102.5 212.4 - -

PIII(D191) 13 13 100 75.3 100 579.3 292.4 1147.5 13 8 61.5 31.6 86.1

Q-PAN-1B Group 1 PII(D182) 10 10 100 69.2 100 242.4 168.0 349.7 - -

PIII(D191) 9 9 100 66.4 100 285.0 167.2 485.8 9 0 0.0 0.0 33.6

Q-PAN-1C Group 2 PII(D182) 13 13 100 75.3 100 140.0 102.3 191.6 - -

PIII(D191) 12 12 100 73.5 100 652.0 416.3 1021.2 12 8 66.7 34.9 90.1 Q-PAN-1C Group 1 PII(D182) 11 11 100 71.5 100 273.2 156.9 475.9 - -

PIII(D191) 9 9 100 66.4 100 244.5 112.8 529.8 9 0 0.0 0.0 33.6

Q-PAN-1D Group 2 PII(D182) 10 10 100 69.2 100 247.8 116.4 527.2 - -

PIII(D191) 10 10 100 69.2 100 946.2 468.3 1911.9 10 5 50.0 18.7 81.3

Q-PAN-1D Group 1 PII(D182) 13 13 100 75.3 100 251.6 160.8 393.7 - -

PIII(D191) 10 10 100 69.2 100 260.0 125.1 540.1 10 0 0.0 0.0 30.8

Q-PAN-2 Group 2 PII(D182) 12 12 100 73.5 100 95.2 62.3 145.6 - -

PIII(D191) 12 12 100 73.5 100 205.7 116.2 364.0 12 3 25.0 5.5 57.2

Q-PAN-2 Group 1 PII(D182) 10 10 100 69.2 100 139.3 87.1 222.9 - -

PIII(D191) 10 10 100 69.2 100 129.9 87.9 192.0 10 0 0.0 0.0 30.8

Placebo PII(D182) 45 43 95.6 84.9 99.5 66.0 53.6 81.3 - -

PIII(D191) 43 38 88.4 74.9 96.1 56.5 45.2 70.7 43 0 0.0 0.0 8.2

Booster vaccine response defined as : For initially seronegative subjects at Day 182, antibody titer ≥ 56 at post-vaccination For initially seropositive subjects at Day 182, antibody titer at post-vaccination ≥ 4 fold the pre-vaccination antibody titer GMT=geometric mean antibody titer calculated on all subjects N = Number of subjects with results available (for GMT and seropositivity) N’= Number of subjects with both pre and post results available (for vaccine response) n/% = Number/percentage of subjects with titer equal to or above specified value n’/% = Number/percentage of responders 95% CI = 95% confidence interval: LL = Lower Limit UL = Upper Limit PII(D182) = Pre Booster-vaccination at Day 182 PIII(D191) = Post Booster-vaccination at Day 191 Secondary Outcome Variable(s): Seropositivity rates and GMTs for neutralizing antibodies against Flu A/chicken/Hong Kong/G9/97 (H9N2) (ATP cohort for immunogenicity at Day 42) – Immune subset

≥ 1: 28 GMT

95% CI 95% CI Antibody Group Timing N n % LL UL Value LL UL

Flu A/chicken/Hong Kong/G9/97 (H9N2)

Q-PAN-1A PRE 26 24 92.3 74.9 99.1 58.0 43.8 76.8

PI(D21) 25 25 100 86.3 100 234.5 161.3 340.9

Q-PAN-1B PRE 24 19 79.2 57.8 92.9 59.8 40.6 88.1

PI(D21) 24 24 100 85.8 100 195.8 140.2 273.4

Q-PAN-1C PRE 25 22 88.0 68.8 97.5 50.5 36.0 70.9

PI(D21) 25 25 100 86.3 100 220.1 159.1 304.5

Q-PAN-1D PRE 25 20 80.0 59.3 93.2 53.4 37.6 75.9

PI(D21) 25 25 100 86.3 100 252.7 178.5 357.6

Q-PAN-2 PRE 24 19 79.2 57.8 92.9 50.3 35.3 71.6

PI(D21) 24 24 100 85.8 100 146.8 106.6 202.2

Placebo PRE 46 40 87.0 73.7 95.1 52.4 42.5 64.7

PI(D21) 45 38 84.4 70.5 93.5 47.0 38.4 57.6

GMT = geometric mean antibody titer calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titer within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit Pre = Pre-vaccination 1 at Day 0 PI(D21) = Pre-vaccination 2 at Day 21 PII(D42) = Post-vaccination 2 at Day 42

Secondary Outcome Variable(s): VRR for neutralizing antibodies against Flu A/chicken/Hong Kong/G9/97 (H9N2) at Day 21 (ATP cohort for immunogenicity at Day 21) – Immune subset

Vaccine response 95% CI

Group Pre-vaccination status N n % LL UL

Q-PAN-1A S- 2 2 100 15.8 100

S+ 23 11 47.8 26.8 69.4

Total 25 13 52.0 31.3 72.2

Q-PAN-1B S- 5 5 100 47.8 100

S+ 19 5 26.3 9.1 51.2

Total 24 10 41.7 22.1 63.4

Q-PAN-1C S- 3 3 100 29.2 100

S+ 22 12 54.5 32.2 75.6

Total 25 15 60.0 38.7 78.9

Q-PAN-1D S- 5 5 100 47.8 100

S+ 20 8 40.0 19.1 63.9

Total 25 13 52.0 31.3 72.2

Q-PAN-2 S- 5 5 100 47.8 100

S+ 19 5 26.3 9.1 51.2

Total 24 10 41.7 22.1 63.4

Placebo S- 6 0 0.0 0.0 45.9

S+ 39 0 0.0 0.0 9.0

Total 45 0 0.0 0.0 7.9

S- = seronegative subjects (antibody titer < 1:28 for Flu A/chicken/Hong Kong/G9/97 (H9N2) Ab) prior to vaccination S+ = seropositive subjects (antibody titer ≥ 1:28 for Flu A/chicken/Hong Kong/G9/97 (H9N2) Ab) prior to vaccination Total = subjects either seropositive or seronegative at pre-vaccination Vaccine response defined as: For initially seronegative subjects, antibody titer ≥ 1: 56 at Pre-vaccination 2 (Day 21) For initially seropositive subjects, antibody titer at Pre-vaccination 2 (Day 21) ≥ 4 fold the pre-vaccination antibody titer N = number of subjects with both pre- and post-vaccination results available n/% = number/percentage of responders 95% CI = exact 95% confidence interval, LL = Lower Limit, UL = Upper Limit

Secondary Outcome Variable(s): Number (%) of subjects reporting solicited local symptoms during the 7-day (Days 0-6) post-vaccination period following each dose and across doses (Total Vaccinated cohort)

Q-PAN-1A Group 1 Q-PAN-1B Group 1 Q-PAN-1C Group 1 Q-PAN-1D Group 1 Q-PAN-2 Group 1

95 % CI 95 % CI 95 % CI 95 % CI 95 % CI

Symptom Intensity N n % LL UL N n % LL UL N n % LL UL N n % LL UL N n % LL UL

Dose 1 Pain Any 30 22 73.3 54.1 87.7 30 22 73.3 54.1 87.7 30 26 86.7 69.3 96.2 30 19 63.3 43.9 80.1 29 9 31.0 15.3 50.8

Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9

Redness Any 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 29 0 0.0 0.0 11.9

>100mm 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9

Swelling Any 30 1 3.3 0.1 17.2 30 1 3.3 0.1 17.2 30 2 6.7 0.8 22.1 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9

>100mm 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9

Dose 2

Pain Any 31 22 71.0 52.0 85.8 29 18 62.1 42.3 79.3 30 19 63.3 43.9 80.1 29 18 62.1 42.3 79.3 29 9 31.0 15.3 50.8

Grade 3 31 1 3.2 0.1 16.7 29 1 3.4 0.1 17.8 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 29 1 3.4 0.1 17.8

Redness Any 31 0 0.0 0.0 11.2 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 29 1 3.4 0.1 17.8 29 0 0.0 0.0 11.9

>100mm 31 0 0.0 0.0 11.2 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 29 0 0.0 0.0 11.9

Swelling Any 31 1 3.2 0.1 16.7 29 0 0.0 0.0 11.9 30 2 6.7 0.8 22.1 29 2 6.9 0.8 22.8 29 1 3.4 0.1 17.8

>100mm 31 0 0.0 0.0 11.2 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 29 0 0.0 0.0 11.9

Dose 3 Pain Any 29 5 17.2 5.8 35.8 28 4 14.3 4.0 32.7 27 5 18.5 6.3 38.1 26 3 11.5 2.4 30.2 28 1 3.6 0.1 18.3

Grade 3 29 0 0.0 0.0 11.9 28 1 3.6 0.1 18.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2 28 0 0.0 0.0 12.3

Redness Any 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2 28 0 0.0 0.0 12.3

>100mm 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2 28 0 0.0 0.0 12.3

Swelling Any 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2 28 0 0.0 0.0 12.3

>100mm 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2 28 0 0.0 0.0 12.3

Across doses

Pain Any 31 27 87.1 70.2 96.4 30 24 80.0 61.4 92.3 30 26 86.7 69.3 96.2 30 22 73.3 54.1 87.7 30 12 40.0 22.7 59.4

Grade 3 31 1 3.2 0.1 16.7 30 2 6.7 0.8 22.1 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2

Redness Any 31 1 3.2 0.1 16.7 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 2 6.7 0.8 22.1 30 0 0.0 0.0 11.6

>100mm 31 0 0.0 0.0 11.2 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Swelling Any 31 2 6.5 0.8 21.4 30 1 3.3 0.1 17.2 30 3 10.0 2.1 26.5 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2

>100mm 31 0 0.0 0.0 11.2 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 Q-PAN-1A Group 2 Q-PAN-1B Group 2 Q-PAN-1C Group 2 Q-PAN-1D Group 2 Q-PAN-2 Group 2

95 % CI 95 % CI 95 % CI 95 % CI 95 % CI

Symptom Intensity N n % LL UL N n % LL UL N n % LL UL N n % LL UL N n % LL UL

Dose 1

Pain Any 30 20 66.7 47.2 82.7 30 18 60.0 40.6 77.3 29 24 82.8 64.2 94.2 30 19 63.3 43.9 80.1 30 7 23.3 9.9 42.3

Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 Redness Any 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 1 3.4 0.1 17.8 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

>100mm 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Swelling Any 30 2 6.7 0.8 22.1 30 0 0.0 0.0 11.6 29 2 6.9 0.8 22.8 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

>100mm 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Dose 2

Pain Any 28 21 75.0 55.1 89.3 30 22 73.3 54.1 87.7 26 19 73.1 52.2 88.4 29 15 51.7 32.5 70.6 28 3 10.7 2.3 28.2

Grade 3 28 1 3.6 0.1 18.3 30 1 3.3 0.1 17.2 26 1 3.8 0.1 19.6 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3

Redness Any 28 0 0.0 0.0 12.3 30 1 3.3 0.1 17.2 26 1 3.8 0.1 19.6 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3

>100mm 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3

Swelling Any 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 2 7.7 0.9 25.1 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3

>100mm 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 Dose 3

Pain Any 23 16 69.6 47.1 86.8 28 22 78.6 59.0 91.7 26 19 73.1 52.2 88.4 26 17 65.4 44.3 82.8 23 3 13.0 2.8 33.6

Grade 3 23 1 4.3 0.1 21.9 28 1 3.6 0.1 18.3 26 0 0.0 0.0 13.2 26 0 0.0 0.0 13.2 23 0 0.0 0.0 14.8

Redness Any 23 1 4.3 0.1 21.9 28 0 0.0 0.0 12.3 26 0 0.0 0.0 13.2 26 1 3.8 0.1 19.6 23 1 4.3 0.1 21.9

>100mm 23 0 0.0 0.0 14.8 28 0 0.0 0.0 12.3 26 0 0.0 0.0 13.2 26 0 0.0 0.0 13.2 23 0 0.0 0.0 14.8

Swelling Any 23 1 4.3 0.1 21.9 28 1 3.6 0.1 18.3 26 1 3.8 0.1 19.6 26 0 0.0 0.0 13.2 23 0 0.0 0.0 14.8

>100mm 23 0 0.0 0.0 14.8 28 0 0.0 0.0 12.3 26 0 0.0 0.0 13.2 26 0 0.0 0.0 13.2 23 0 0.0 0.0 14.8

Across doses

Pain Any 30 26 86.7 69.3 96.2 30 25 83.3 65.3 94.4 29 25 86.2 68.3 96.1 30 25 83.3 65.3 94.4 30 9 30.0 14.7 49.4

Grade 3 30 3 10.0 2.1 26.5 30 2 6.7 0.8 22.1 29 1 3.4 0.1 17.8 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Redness Any 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2 29 2 6.9 0.8 22.8 30 1 3.3 0.1 17.2 30 1 3.3 0.1 17.2

>100mm 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Swelling Any 30 3 10.0 2.1 26.5 30 1 3.3 0.1 17.2 29 3 10.3 2.2 27.4 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

>100mm 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Placebo Group 95% CI

Symptom Intensity N n % LL UL

Dose 1 Pain Any 118 10 8.5 4.1 15.0

Grade 3 118 0 0.0 0.0 3.1

Redness Any 118 0 0.0 0.0 3.1 >100mm 118 0 0.0 0.0 3.1

Swelling Any 118 0 0.0 0.0 3.1

>100mm 118 0 0.0 0.0 3.1

Dose 2 Pain Any 111 10 9.0 4.4 15.9

Grade 3 111 0 0.0 0.0 3.3

Redness Any 111 0 0.0 0.0 3.3 >100mm 111 0 0.0 0.0 3.3

Swelling Any 111 0 0.0 0.0 3.3

>100mm 111 0 0.0 0.0 3.3

Dose 3 Pain Any 112 7 6.3 2.5 12.5

Grade 3 112 0 0.0 0.0 3.2

Redness Any 112 0 0.0 0.0 3.2 >100mm 112 0 0.0 0.0 3.2

Swelling Any 112 0 0.0 0.0 3.2

>100mm 112 0 0.0 0.0 3.2 Across doses

Pain Any 118 20 16.9 10.7 25.0

Grade 3 118 0 0.0 0.0 3.1

Redness Any 118 0 0.0 0.0 3.1 >100mm 118 0 0.0 0.0 3.1

Swelling Any 118 0 0.0 0.0 3.1

>100mm 118 0 0.0 0.0 3.1 N = number of subjects with at least one documented dose n/% = number/percentage of subjects reporting the symptom at least once 95% CI = exact 95% confidence interval; LL = Lower Limit; UL = Upper Limit

Any = occurrence of any local symptom regardless of intensity grade Grade 3 Pain = Significant pain at rest, which prevented normal every day activities.

Secondary Outcome Variable(s): Number (%) of subjects reporting solicited general symptoms during the 7-day (Days 0-6) post-vaccination period following each dose and across doses (Total Vaccinated cohort)

Q-PAN-1A Group 1 Q-PAN-1B Group 1 Q-PAN-1C Group 1 Q-PAN-1D Group 1

95 % CI 95 % CI 95 % CI 95 % CI

Symptom Intensity/Relationship N n % LL UL N n % LL UL N n % LL UL N n % LL UL

Dose 1 Fatigue Any 30 7 23.3 9.9 42.3 30 13 43.3 25.5 62.6 30 12 40.0 22.7 59.4 30 6 20.0 7.7 38.6

Grade 3 30 1 3.3 0.1 17.2 30 2 6.7 0.8 22.1 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2

Related 30 7 23.3 9.9 42.3 30 11 36.7 19.9 56.1 30 12 40.0 22.7 59.4 30 6 20.0 7.7 38.6

Gastrointestinal symptoms*

Any 30 3 10.0 2.1 26.5 30 6 20.0 7.7 38.6 30 5 16.7 5.6 34.7 30 4 13.3 3.8 30.7

Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 1 3.3 0.1 17.2 Related 30 2 6.7 0.8 22.1 30 5 16.7 5.6 34.7 30 4 13.3 3.8 30.7 30 3 10.0 2.1 26.5

Headache Any 30 10 33.3 17.3 52.8 30 15 50.0 31.3 68.7 30 9 30.0 14.7 49.4 30 8 26.7 12.3 45.9

Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6

Related 30 8 26.7 12.3 45.9 30 14 46.7 28.3 65.7 30 8 26.7 12.3 45.9 30 7 23.3 9.9 42.3

Increased sweating

Any 30 2 6.7 0.8 22.1 30 3 10.0 2.1 26.5 30 6 20.0 7.7 38.6 30 3 10.0 2.1 26.5 Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6

Related 30 1 3.3 0.1 17.2 30 3 10.0 2.1 26.5 30 5 16.7 5.6 34.7 30 3 10.0 2.1 26.5

Joint pain Any 30 3 10.0 2.1 26.5 30 6 20.0 7.7 38.6 30 6 20.0 7.7 38.6 30 4 13.3 3.8 30.7

Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Related 30 3 10.0 2.1 26.5 30 5 16.7 5.6 34.7 30 6 20.0 7.7 38.6 30 2 6.7 0.8 22.1

Muscle ache Any 30 7 23.3 9.9 42.3 30 11 36.7 19.9 56.1 30 10 33.3 17.3 52.8 30 8 26.7 12.3 45.9 Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Related 30 7 23.3 9.9 42.3 30 10 33.3 17.3 52.8 30 9 30.0 14.7 49.4 30 6 20.0 7.7 38.6

Shivering (Chills) Any 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2 30 5 16.7 5.6 34.7 30 2 6.7 0.8 22.1 Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6

Related 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2 30 5 16.7 5.6 34.7 30 2 6.7 0.8 22.1

Fever ≥38.0°C 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6

≥39.0°C 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Related 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 Dose 2

Fatigue Any 31 12 38.7 21.8 57.8 29 9 31.0 15.3 50.8 30 6 20.0 7.7 38.6 29 3 10.3 2.2 27.4

Grade 3 31 3 9.7 2.0 25.8 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9

Related 31 10 32.3 16.7 51.4 29 9 31.0 15.3 50.8 30 6 20.0 7.7 38.6 29 3 10.3 2.2 27.4

Gastrointestinal symptoms*

Any 31 3 9.7 2.0 25.8 29 4 13.8 3.9 31.7 30 3 10.0 2.1 26.5 29 3 10.3 2.2 27.4 Grade 3 31 0 0.0 0.0 11.2 29 1 3.4 0.1 17.8 30 1 3.3 0.1 17.2 29 0 0.0 0.0 11.9

Related 31 3 9.7 2.0 25.8 29 2 6.9 0.8 22.8 30 2 6.7 0.8 22.1 29 3 10.3 2.2 27.4

Headache Any 31 11 35.5 19.2 54.6 29 7 24.1 10.3 43.5 30 6 20.0 7.7 38.6 29 8 27.6 12.7 47.2

Grade 3 31 1 3.2 0.1 16.7 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2 29 1 3.4 0.1 17.8

Related 31 10 32.3 16.7 51.4 29 7 24.1 10.3 43.5 30 4 13.3 3.8 30.7 29 8 27.6 12.7 47.2

Increased sweating

Any 31 1 3.2 0.1 16.7 29 4 13.8 3.9 31.7 30 3 10.0 2.1 26.5 29 2 6.9 0.8 22.8 Grade 3 31 1 3.2 0.1 16.7 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9

Related 31 1 3.2 0.1 16.7 29 4 13.8 3.9 31.7 30 2 6.7 0.8 22.1 29 2 6.9 0.8 22.8

Joint pain Any 31 6 19.4 7.5 37.5 29 5 17.2 5.8 35.8 30 3 10.0 2.1 26.5 29 1 3.4 0.1 17.8

Grade 3 31 1 3.2 0.1 16.7 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9

Related 31 6 19.4 7.5 37.5 29 4 13.8 3.9 31.7 30 3 10.0 2.1 26.5 29 1 3.4 0.1 17.8

Muscle ache Any 31 13 41.9 24.5 60.9 29 12 41.4 23.5 61.1 30 5 16.7 5.6 34.7 29 5 17.2 5.8 35.8

Grade 3 31 3 9.7 2.0 25.8 29 1 3.4 0.1 17.8 30 0 0.0 0.0 11.6 29 1 3.4 0.1 17.8

Related 31 12 38.7 21.8 57.8 29 11 37.9 20.7 57.7 30 5 16.7 5.6 34.7 29 5 17.2 5.8 35.8

Shivering (Chills) Any 31 7 22.6 9.6 41.1 29 0 0.0 0.0 11.9 30 3 10.0 2.1 26.5 29 2 6.9 0.8 22.8 Grade 3 31 1 3.2 0.1 16.7 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9

Related 31 7 22.6 9.6 41.1 29 0 0.0 0.0 11.9 30 3 10.0 2.1 26.5 29 2 6.9 0.8 22.8

Fever ≥38.0°C 31 2 6.5 0.8 21.4 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2 29 0 0.0 0.0 11.9

≥39.0°C 31 1 3.2 0.1 16.7 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9

Related 31 2 6.5 0.8 21.4 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2 29 0 0.0 0.0 11.9

Dose 3 Fatigue Any 29 6 20.7 8.0 39.7 28 6 21.4 8.3 41.0 27 6 22.2 8.6 42.3 26 4 15.4 4.4 34.9

Grade 3 29 0 0.0 0.0 11.9 28 1 3.6 0.1 18.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Related 29 5 17.2 5.8 35.8 28 4 14.3 4.0 32.7 27 4 14.8 4.2 33.7 26 4 15.4 4.4 34.9

Gastrointestinal symptoms*

Any 29 1 3.4 0.1 17.8 28 2 7.1 0.9 23.5 27 3 11.1 2.4 29.2 26 1 3.8 0.1 19.6 Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Related 29 1 3.4 0.1 17.8 28 1 3.6 0.1 18.3 27 2 7.4 0.9 24.3 26 0 0.0 0.0 13.2

Headache Any 29 6 20.7 8.0 39.7 28 5 17.9 6.1 36.9 27 5 18.5 6.3 38.1 26 4 15.4 4.4 34.9

Grade 3 29 0 0.0 0.0 11.9 28 1 3.6 0.1 18.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Related 29 4 13.8 3.9 31.7 28 2 7.1 0.9 23.5 27 2 7.4 0.9 24.3 26 4 15.4 4.4 34.9

Increased sweating Any 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 1 3.8 0.1 19.6

Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Related 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Joint pain Any 29 3 10.3 2.2 27.4 28 1 3.6 0.1 18.3 27 1 3.7 0.1 19.0 26 0 0.0 0.0 13.2

Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Related 29 3 10.3 2.2 27.4 28 1 3.6 0.1 18.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Muscle ache Any 29 3 10.3 2.2 27.4 28 1 3.6 0.1 18.3 27 6 22.2 8.6 42.3 26 2 7.7 0.9 25.1

Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Related 29 3 10.3 2.2 27.4 28 1 3.6 0.1 18.3 27 2 7.4 0.9 24.3 26 1 3.8 0.1 19.6

Shivering (Chills) Any 29 1 3.4 0.1 17.8 28 2 7.1 0.9 23.5 27 2 7.4 0.9 24.3 26 2 7.7 0.9 25.1

Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Related 29 1 3.4 0.1 17.8 28 1 3.6 0.1 18.3 27 1 3.7 0.1 19.0 26 1 3.8 0.1 19.6

Fever ≥38.0°C 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 1 3.8 0.1 19.6

≥39.0°C 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 1 3.8 0.1 19.6

Related 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 27 0 0.0 0.0 12.8 26 0 0.0 0.0 13.2

Across doses

Fatigue Any 31 16 51.6 33.1 69.8 30 16 53.3 34.3 71.7 30 13 43.3 25.5 62.6 30 8 26.7 12.3 45.9

Grade 3 31 4 12.9 3.6 29.8 30 3 10.0 2.1 26.5 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2

Related 31 15 48.4 30.2 66.9 30 15 50.0 31.3 68.7 30 12 40.0 22.7 59.4 30 8 26.7 12.3 45.9

Gastrointestinal symptoms*

Any 31 5 16.1 5.5 33.7 30 9 30.0 14.7 49.4 30 10 33.3 17.3 52.8 30 6 20.0 7.7 38.6

Grade 3 31 0 0.0 0.0 11.2 30 1 3.3 0.1 17.2 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2

Related 31 4 12.9 3.6 29.8 30 8 26.7 12.3 45.9 30 7 23.3 9.9 42.3 30 5 16.7 5.6 34.7

Headache Any 31 16 51.6 33.1 69.8 30 19 63.3 43.9 80.1 30 12 40.0 22.7 59.4 30 12 40.0 22.7 59.4

Grade 3 31 1 3.2 0.1 16.7 30 1 3.3 0.1 17.2 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2

Related 31 14 45.2 27.3 64.0 30 17 56.7 37.4 74.5 30 9 30.0 14.7 49.4 30 11 36.7 19.9 56.1

Increased sweating Any 31 3 9.7 2.0 25.8 30 6 20.0 7.7 38.6 30 7 23.3 9.9 42.3 30 5 16.7 5.6 34.7

Grade 3 31 1 3.2 0.1 16.7 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6

Related 31 2 6.5 0.8 21.4 30 6 20.0 7.7 38.6 30 6 20.0 7.7 38.6 30 5 16.7 5.6 34.7

Joint pain Any 31 9 29.0 14.2 48.0 30 9 30.0 14.7 49.4 30 7 23.3 9.9 42.3 30 5 16.7 5.6 34.7

Grade 3 31 2 6.5 0.8 21.4 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6

Related 31 9 29.0 14.2 48.0 30 8 26.7 12.3 45.9 30 6 20.0 7.7 38.6 30 3 10.0 2.1 26.5

Muscle ache Any 31 17 54.8 36.0 72.7 30 15 50.0 31.3 68.7 30 12 40.0 22.7 59.4 30 10 33.3 17.3 52.8

Grade 3 31 4 12.9 3.6 29.8 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 Related 31 17 54.8 36.0 72.7 30 15 50.0 31.3 68.7 30 10 33.3 17.3 52.8 30 8 26.7 12.3 45.9

Shivering (Chills) Any 31 8 25.8 11.9 44.6 30 2 6.7 0.8 22.1 30 6 20.0 7.7 38.6 30 3 10.0 2.1 26.5

Grade 3 31 2 6.5 0.8 21.4 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6

Related 31 8 25.8 11.9 44.6 30 1 3.3 0.1 17.2 30 6 20.0 7.7 38.6 30 3 10.0 2.1 26.5

Fever ≥38.0°C 31 2 6.5 0.8 21.4 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 1 3.3 0.1 17.2

≥39.0°C 31 1 3.2 0.1 16.7 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2

Related 31 2 6.5 0.8 21.4 30 0 0.0 0.0 11.6 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6

Q-PAN-1A Group 2 Q-PAN-1B Group 2 Q-PAN-1C Group 2 Q-PAN-1D Group 2

95 % CI 95 % CI 95 % CI 95 % CI

Symptom Type N n % LL UL N n % LL UL N n % LL UL N n % LL UL

Dose 1 Fatigue Any 30 9 30.0 14.7 49.4 30 6 20.0 7.7 38.6 29 9 31.0 15.3 50.8 30 8 26.7 12.3 45.9

Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2

Related 30 7 23.3 9.9 42.3 30 5 16.7 5.6 34.7 29 8 27.6 12.7 47.2 30 6 20.0 7.7 38.6

Gastrointestinal symptoms*

Any 30 4 13.3 3.8 30.7 30 4 13.3 3.8 30.7 29 3 10.3 2.2 27.4 30 2 6.7 0.8 22.1

Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 Related 30 2 6.7 0.8 22.1 30 3 10.0 2.1 26.5 29 1 3.4 0.1 17.8 30 2 6.7 0.8 22.1

Headache Any 30 9 30.0 14.7 49.4 30 9 30.0 14.7 49.4 29 9 31.0 15.3 50.8 30 5 16.7 5.6 34.7

Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6

Related 30 8 26.7 12.3 45.9 30 8 26.7 12.3 45.9 29 7 24.1 10.3 43.5 30 5 16.7 5.6 34.7

Increased sweating

Any 30 3 10.0 2.1 26.5 30 1 3.3 0.1 17.2 29 2 6.9 0.8 22.8 30 2 6.7 0.8 22.1 Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6

Related 30 1 3.3 0.1 17.2 30 1 3.3 0.1 17.2 29 2 6.9 0.8 22.8 30 2 6.7 0.8 22.1

Joint pain Any 30 5 16.7 5.6 34.7 30 1 3.3 0.1 17.2 29 2 6.9 0.8 22.8 30 4 13.3 3.8 30.7

Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2

Related 30 3 10.0 2.1 26.5 30 1 3.3 0.1 17.2 29 1 3.4 0.1 17.8 30 3 10.0 2.1 26.5

Muscle ache Any 30 8 26.7 12.3 45.9 30 6 20.0 7.7 38.6 29 7 24.1 10.3 43.5 30 8 26.7 12.3 45.9

Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2

Related 30 7 23.3 9.9 42.3 30 6 20.0 7.7 38.6 29 6 20.7 8.0 39.7 30 7 23.3 9.9 42.3

Shivering (Chills) Any 30 4 13.3 3.8 30.7 30 1 3.3 0.1 17.2 29 4 13.8 3.9 31.7 30 3 10.0 2.1 26.5

Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6

Related 30 3 10.0 2.1 26.5 30 0 0.0 0.0 11.6 29 3 10.3 2.2 27.4 30 3 10.0 2.1 26.5

Fever ≥38.0°C 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6

≥39.0°C 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6

Related 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6

Dose 2

Fatigue Any 28 5 17.9 6.1 36.9 30 10 33.3 17.3 52.8 26 9 34.6 17.2 55.7 29 8 27.6 12.7 47.2

Grade 3 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 1 3.4 0.1 17.8

Related 28 5 17.9 6.1 36.9 30 7 23.3 9.9 42.3 26 8 30.8 14.3 51.8 29 8 27.6 12.7 47.2

Gastrointestinal symptoms*

Any 28 3 10.7 2.3 28.2 30 2 6.7 0.8 22.1 26 0 0.0 0.0 13.2 29 2 6.9 0.8 22.8

Grade 3 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 0 0.0 0.0 11.9

Related 28 3 10.7 2.3 28.2 30 1 3.3 0.1 17.2 26 0 0.0 0.0 13.2 29 2 6.9 0.8 22.8

Headache Any 28 9 32.1 15.9 52.4 30 9 30.0 14.7 49.4 26 11 42.3 23.4 63.1 29 5 17.2 5.8 35.8

Grade 3 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 1 3.4 0.1 17.8

Related 28 6 21.4 8.3 41.0 30 7 23.3 9.9 42.3 26 11 42.3 23.4 63.1 29 4 13.8 3.9 31.7

Increased sweating

Any 28 2 7.1 0.9 23.5 30 1 3.3 0.1 17.2 26 6 23.1 9.0 43.6 29 3 10.3 2.2 27.4

Grade 3 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 1 3.8 0.1 19.6 29 0 0.0 0.0 11.9 Related 28 2 7.1 0.9 23.5 30 1 3.3 0.1 17.2 26 6 23.1 9.0 43.6 29 3 10.3 2.2 27.4

Joint pain Any 28 4 14.3 4.0 32.7 30 2 6.7 0.8 22.1 26 4 15.4 4.4 34.9 29 5 17.2 5.8 35.8

Grade 3 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 0 0.0 0.0 11.9

Related 28 4 14.3 4.0 32.7 30 1 3.3 0.1 17.2 26 4 15.4 4.4 34.9 29 5 17.2 5.8 35.8

Muscle ache Any 28 10 35.7 18.6 55.9 30 7 23.3 9.9 42.3 26 10 38.5 20.2 59.4 29 10 34.5 17.9 54.3

Grade 3 28 1 3.6 0.1 18.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 0 0.0 0.0 11.9

Related 28 10 35.7 18.6 55.9 30 5 16.7 5.6 34.7 26 10 38.5 20.2 59.4 29 10 34.5 17.9 54.3

Shivering (Chills) Any 28 3 10.7 2.3 28.2 30 3 10.0 2.1 26.5 26 7 26.9 11.6 47.8 29 3 10.3 2.2 27.4

Grade 3 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 1 3.8 0.1 19.6 29 0 0.0 0.0 11.9

Related 28 3 10.7 2.3 28.2 30 2 6.7 0.8 22.1 26 7 26.9 11.6 47.8 29 2 6.9 0.8 22.8

Fever (°C) ≥38.0°C 28 1 3.6 0.1 18.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 0 0.0 0.0 11.9

≥39.0°C 28 0 0.0 0.0 12.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 0 0.0 0.0 11.9

Related 28 1 3.6 0.1 18.3 30 0 0.0 0.0 11.6 26 0 0.0 0.0 13.2 29 0 0.0 0.0 11.9

Dose 3

Fatigue Any 23 7 30.4 13.2 52.9 28 6 21.4 8.3 41.0 26 9 34.6 17.2 55.7 26 7 26.9 11.6 47.8

Grade 3 23 1 4.3 0.1 21.9 28 0 0.0 0.0 12.3 26 0 0.0 0.0 13.2 26 0 0.0 0.0 13.2

Related 23 5 21.7 7.5 43.7 28 4 14.3 4.0 32.7 26 8 30.8 14.3 51.8 26 6 23.1 9.0 43.6

Gastrointestinal symptoms*

Any 23 5 21.7 7.5 43.7 28 2 7.1 0.9 23.5 26 1 3.8 0.1 19.6 26 4 15.4 4.4 34.9

Grade 3 23 1 4.3 0.1 21.9 28 0 0.0 0.0 12.3 26 0 0.0 0.0 13.2 26 0 0.0 0.0 13.2

Related 23 3 13.0 2.8 33.6 28 1 3.6 0.1 18.3 26 1 3.8 0.1 19.6 26 1 3.8 0.1 19.6

Headache Any 23 10 43.5 23.2 65.5 28 3 10.7 2.3 28.2 26 8 30.8 14.3 51.8 26 6 23.1 9.0 43.6

Grade 3 23 3 13.0 2.8 33.6 28 0 0.0 0.0 12.3 26 1 3.8 0.1 19.6 26 0 0.0 0.0 13.2

Related 23 8 34.8 16.4 57.3 28 3 10.7 2.3 28.2 26 6 23.1 9.0 43.6 26 4 15.4 4.4 34.9

Increased sweating

Any 23 2 8.7 1.1 28.0 28 1 3.6 0.1 18.3 26 3 11.5 2.4 30.2 26 1 3.8 0.1 19.6

Grade 3 23 0 0.0 0.0 14.8 28 0 0.0 0.0 12.3 26 1 3.8 0.1 19.6 26 0 0.0 0.0 13.2 Related 23 2 8.7 1.1 28.0 28 1 3.6 0.1 18.3 26 3 11.5 2.4 30.2 26 1 3.8 0.1 19.6

Joint pain Any 23 2 8.7 1.1 28.0 28 4 14.3 4.0 32.7 26 1 3.8 0.1 19.6 26 4 15.4 4.4 34.9

Grade 3 23 0 0.0 0.0 14.8 28 0 0.0 0.0 12.3 26 0 0.0 0.0 13.2 26 0 0.0 0.0 13.2

Related 23 2 8.7 1.1 28.0 28 3 10.7 2.3 28.2 26 1 3.8 0.1 19.6 26 3 11.5 2.4 30.2

Muscle ache Any 23 6 26.1 10.2 48.4 28 6 21.4 8.3 41.0 26 8 30.8 14.3 51.8 26 11 42.3 23.4 63.1

Grade 3 23 1 4.3 0.1 21.9 28 0 0.0 0.0 12.3 26 0 0.0 0.0 13.2 26 0 0.0 0.0 13.2

Related 23 5 21.7 7.5 43.7 28 5 17.9 6.1 36.9 26 8 30.8 14.3 51.8 26 8 30.8 14.3 51.8

Shivering (Chills) Any 23 3 13.0 2.8 33.6 28 1 3.6 0.1 18.3 26 2 7.7 0.9 25.1 26 4 15.4 4.4 34.9

Grade 3 23 1 4.3 0.1 21.9 28 0 0.0 0.0 12.3 26 1 3.8 0.1 19.6 26 0 0.0 0.0 13.2

Related 23 3 13.0 2.8 33.6 28 1 3.6 0.1 18.3 26 2 7.7 0.9 25.1 26 3 11.5 2.4 30.2

Fever ≥38.0°C 23 0 0.0 0.0 14.8 28 0 0.0 0.0 12.3 26 1 3.8 0.1 19.6 26 0 0.0 0.0 13.2

≥39.0°C 23 0 0.0 0.0 14.8 28 0 0.0 0.0 12.3 26 1 3.8 0.1 19.6 26 0 0.0 0.0 13.2

Related 23 0 0.0 0.0 14.8 28 0 0.0 0.0 12.3 26 1 3.8 0.1 19.6 26 0 0.0 0.0 13.2

Across doses

Fatigue Any 30 14 46.7 28.3 65.7 30 13 43.3 25.5 62.6 29 16 55.2 35.7 73.6 30 14 46.7 28.3 65.7

Grade 3 30 2 6.7 0.8 22.1 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 2 6.7 0.8 22.1

Related 30 11 36.7 19.9 56.1 30 11 36.7 19.9 56.1 29 13 44.8 26.4 64.3 30 12 40.0 22.7 59.4

Gastrointestinal symptoms*

Any 30 8 26.7 12.3 45.9 30 7 23.3 9.9 42.3 29 4 13.8 3.9 31.7 30 6 20.0 7.7 38.6

Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6

Related 30 6 20.0 7.7 38.6 30 5 16.7 5.6 34.7 29 2 6.9 0.8 22.8 30 4 13.3 3.8 30.7

Headache Any 30 14 46.7 28.3 65.7 30 13 43.3 25.5 62.6 29 16 55.2 35.7 73.6 30 9 30.0 14.7 49.4

Grade 3 30 4 13.3 3.8 30.7 30 0 0.0 0.0 11.6 29 1 3.4 0.1 17.8 30 1 3.3 0.1 17.2

Related 30 12 40.0 22.7 59.4 30 11 36.7 19.9 56.1 29 14 48.3 29.4 67.5 30 9 30.0 14.7 49.4

Increased sweating

Any 30 6 20.0 7.7 38.6 30 3 10.0 2.1 26.5 29 9 31.0 15.3 50.8 30 4 13.3 3.8 30.7

Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 2 6.9 0.8 22.8 30 0 0.0 0.0 11.6

Related 30 4 13.3 3.8 30.7 30 3 10.0 2.1 26.5 29 9 31.0 15.3 50.8 30 4 13.3 3.8 30.7

Joint pain Any 30 7 23.3 9.9 42.3 30 6 20.0 7.7 38.6 29 6 20.7 8.0 39.7 30 9 30.0 14.7 49.4

Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2

Related 30 5 16.7 5.6 34.7 30 5 16.7 5.6 34.7 29 5 17.2 5.8 35.8 30 8 26.7 12.3 45.9

Muscle ache Any 30 15 50.0 31.3 68.7 30 12 40.0 22.7 59.4 29 16 55.2 35.7 73.6 30 17 56.7 37.4 74.5

Grade 3 30 3 10.0 2.1 26.5 30 0 0.0 0.0 11.6 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2

Related 30 14 46.7 28.3 65.7 30 11 36.7 19.9 56.1 29 15 51.7 32.5 70.6 30 16 53.3 34.3 71.7

Shivering (Chills) Any 30 6 20.0 7.7 38.6 30 4 13.3 3.8 30.7 29 9 31.0 15.3 50.8 30 7 23.3 9.9 42.3 Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 2 6.9 0.8 22.8 30 0 0.0 0.0 11.6

Related 30 5 16.7 5.6 34.7 30 3 10.0 2.1 26.5 29 8 27.6 12.7 47.2 30 6 20.0 7.7 38.6

Fever (°C) ≥38.0°C 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 1 3.4 0.1 17.8 30 0 0.0 0.0 11.6

≥39.0°C 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 29 1 3.4 0.1 17.8 30 0 0.0 0.0 11.6

Related 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 29 1 3.4 0.1 17.8 30 0 0.0 0.0 11.6

Q-PAN-2 Group 1 Q-PAN-2 Group 2 Placebo Group

95% CI 95 % CI 95 % CI

Symptom Intensity/Relationship N n % LL UL N n % LL UL N n % LL UL Dose 1

Fatigue Any 29 7 24.1 10.3 43.5 30 11 36.7 19.9 56.1 118 19 16.1 10.0 24.0

Grade 3 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 118 1 0.8 0.0 4.6

Related 29 6 20.7 8.0 39.7 30 10 33.3 17.3 52.8 118 17 14.4 8.6 22.1

Gastrointestinal symptoms*

Any 29 2 6.9 0.8 22.8 30 7 23.3 9.9 42.3 118 8 6.8 3.0 12.9

Grade 3 29 1 3.4 0.1 17.8 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1

Related 29 2 6.9 0.8 22.8 30 6 20.0 7.7 38.6 118 7 5.9 2.4 11.8

Headache Any 29 7 24.1 10.3 43.5 30 9 30.0 14.7 49.4 118 22 18.6 12.1 26.9 Grade 3 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 118 1 0.8 0.0 4.6

Related 29 6 20.7 8.0 39.7 30 9 30.0 14.7 49.4 118 17 14.4 8.6 22.1

Increased sweating Any 29 1 3.4 0.1 17.8 30 2 6.7 0.8 22.1 118 6 5.1 1.9 10.7

Grade 3 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1

Related 29 1 3.4 0.1 17.8 30 2 6.7 0.8 22.1 118 5 4.2 1.4 9.6

Joint pain Any 29 4 13.8 3.9 31.7 30 2 6.7 0.8 22.1 118 5 4.2 1.4 9.6

Grade 3 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1

Related 29 3 10.3 2.2 27.4 30 1 3.3 0.1 17.2 118 5 4.2 1.4 9.6

Muscle ache Any 29 4 13.8 3.9 31.7 30 6 20.0 7.7 38.6 118 12 10.2 5.4 17.1 Grade 3 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1

Related 29 4 13.8 3.9 31.7 30 4 13.3 3.8 30.7 118 12 10.2 5.4 17.1

Shivering (Chills) Any 29 1 3.4 0.1 17.8 30 2 6.7 0.8 22.1 118 3 2.5 0.5 7.3

Grade 3 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1 Related 29 1 3.4 0.1 17.8 30 2 6.7 0.8 22.1 118 2 1.7 0.2 6.0

Fever ≥38.0°C 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2 118 0 0.0 0.0 3.1

≥39.0°C 29 0 0.0 0.0 11.9 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1

Related 29 0 0.0 0.0 11.9 30 1 3.3 0.1 17.2 118 0 0.0 0.0 3.1 Dose 2

Fatigue Any 29 6 20.7 8.0 39.7 28 4 14.3 4.0 32.7 111 13 11.7 6.4 19.2

Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 111 1 0.9 0.0 4.9 Related 29 6 20.7 8.0 39.7 28 4 14.3 4.0 32.7 111 9 8.1 3.8 14.8

Gastrointestinal symptoms*

Any 29 5 17.2 5.8 35.8 28 2 7.1 0.9 23.5 111 5 4.5 1.5 10.2

Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 111 1 0.9 0.0 4.9

Related 29 3 10.3 2.2 27.4 28 2 7.1 0.9 23.5 111 4 3.6 1.0 9.0

Headache Any 29 9 31.0 15.3 50.8 28 2 7.1 0.9 23.5 111 11 9.9 5.1 17.0

Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 111 0 0.0 0.0 3.3

Related 29 7 24.1 10.3 43.5 28 1 3.6 0.1 18.3 111 8 7.2 3.2 13.7

Increased sweating Any 29 3 10.3 2.2 27.4 28 1 3.6 0.1 18.3 111 2 1.8 0.2 6.4 Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 111 0 0.0 0.0 3.3

Related 29 3 10.3 2.2 27.4 28 0 0.0 0.0 12.3 111 2 1.8 0.2 6.4

Joint pain Any 29 3 10.3 2.2 27.4 28 1 3.6 0.1 18.3 111 3 2.7 0.6 7.7 Grade 3 29 1 3.4 0.1 17.8 28 0 0.0 0.0 12.3 111 0 0.0 0.0 3.3

Related 29 3 10.3 2.2 27.4 28 1 3.6 0.1 18.3 111 3 2.7 0.6 7.7

Muscle ache Any 29 4 13.8 3.9 31.7 28 1 3.6 0.1 18.3 111 7 6.3 2.6 12.6

Grade 3 29 2 6.9 0.8 22.8 28 0 0.0 0.0 12.3 111 0 0.0 0.0 3.3 Related 29 4 13.8 3.9 31.7 28 1 3.6 0.1 18.3 111 5 4.5 1.5 10.2

Shivering (Chills) Any 29 2 6.9 0.8 22.8 28 0 0.0 0.0 12.3 111 1 0.9 0.0 4.9

Grade 3 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 111 0 0.0 0.0 3.3

Related 29 2 6.9 0.8 22.8 28 0 0.0 0.0 12.3 111 1 0.9 0.0 4.9

Fever ≥38.0°C 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 111 0 0.0 0.0 3.3

≥39.0°C 29 0 0.0 0.0 11.9 28 0 0.0 0.0 12.3 111 0 0.0 0.0 3.3

Related 29 1 3.4 0.1 17.8 28 0 0.0 0.0 12.3 111 0 0.0 0.0 3.3 Dose 3

Fatigue Any 28 2 7.1 0.9 23.5 23 4 17.4 5.0 38.8 112 8 7.1 3.1 13.6

Grade 3 28 0 0.0 0.0 12.3 23 0 0.0 0.0 14.8 112 0 0.0 0.0 3.2

Related 28 2 7.1 0.9 23.5 23 3 13.0 2.8 33.6 112 5 4.5 1.5 10.1

Gastrointestinal symptoms*

Any 28 2 7.1 0.9 23.5 23 2 8.7 1.1 28.0 112 4 3.6 1.0 8.9

Grade 3 28 0 0.0 0.0 12.3 23 0 0.0 0.0 14.8 112 0 0.0 0.0 3.2

Related 28 1 3.6 0.1 18.3 23 1 4.3 0.1 21.9 112 2 1.8 0.2 6.3

Headache Any 28 7 25.0 10.7 44.9 23 5 21.7 7.5 43.7 112 8 7.1 3.1 13.6 Grade 3 28 0 0.0 0.0 12.3 23 2 8.7 1.1 28.0 112 0 0.0 0.0 3.2

Related 28 5 17.9 6.1 36.9 23 4 17.4 5.0 38.8 112 5 4.5 1.5 10.1

Increased sweating Any 28 1 3.6 0.1 18.3 23 1 4.3 0.1 21.9 112 3 2.7 0.6 7.6 Grade 3 28 0 0.0 0.0 12.3 23 0 0.0 0.0 14.8 112 0 0.0 0.0 3.2

Related 28 1 3.6 0.1 18.3 23 1 4.3 0.1 21.9 112 2 1.8 0.2 6.3

Joint pain Any 28 0 0.0 0.0 12.3 23 0 0.0 0.0 14.8 112 5 4.5 1.5 10.1

Grade 3 28 0 0.0 0.0 12.3 23 0 0.0 0.0 14.8 112 0 0.0 0.0 3.2 Related 28 0 0.0 0.0 12.3 23 0 0.0 0.0 14.8 112 5 4.5 1.5 10.1

Muscle ache Any 28 0 0.0 0.0 12.3 23 1 4.3 0.1 21.9 112 7 6.3 2.5 12.5

Grade 3 28 0 0.0 0.0 12.3 23 0 0.0 0.0 14.8 112 0 0.0 0.0 3.2

Related 28 0 0.0 0.0 12.3 23 1 4.3 0.1 21.9 112 6 5.4 2.0 11.3

Shivering (Chills) Any 28 1 3.6 0.1 18.3 23 0 0.0 0.0 14.8 112 3 2.7 0.6 7.6

Grade 3 28 1 3.6 0.1 18.3 23 0 0.0 0.0 14.8 112 0 0.0 0.0 3.2

Related 28 1 3.6 0.1 18.3 23 0 0.0 0.0 14.8 112 2 1.8 0.2 6.3

Fever ≥38.0°C 28 2 7.1 0.9 23.5 23 0 0.0 0.0 14.8 112 0 0.0 0.0 3.2 ≥39.0°C 28 0 0.0 0.0 12.3 23 0 0.0 0.0 14.8 112 0 0.0 0.0 3.2

Related 28 2 7.1 0.9 23.5 23 0 0.0 0.0 14.8 112 0 0.0 0.0 3.2

Across doses

Fatigue Any 30 11 36.7 19.9 56.1 30 12 40.0 22.7 59.4 118 30 25.4 17.9 34.3 Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 118 2 1.7 0.2 6.0

Related 30 10 33.3 17.3 52.8 30 11 36.7 19.9 56.1 118 24 20.3 13.5 28.7

Gastrointestinal symptoms*

Any 30 7 23.3 9.9 42.3 30 9 30.0 14.7 49.4 118 15 12.7 7.3 20.1 Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 118 1 0.8 0.0 4.6

Related 30 6 20.0 7.7 38.6 30 7 23.3 9.9 42.3 118 12 10.2 5.4 17.1

Headache Any 30 15 50.0 31.3 68.7 30 11 36.7 19.9 56.1 118 33 28.0 20.1 37.0

Grade 3 30 0 0.0 0.0 11.6 30 2 6.7 0.8 22.1 118 1 0.8 0.0 4.6 Related 30 13 43.3 25.5 62.6 30 11 36.7 19.9 56.1 118 26 22.0 14.9 30.6

Increased sweating Any 30 4 13.3 3.8 30.7 30 4 13.3 3.8 30.7 118 11 9.3 4.7 16.1

Grade 3 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1

Related 30 4 13.3 3.8 30.7 30 3 10.0 2.1 26.5 118 9 7.6 3.5 14.0

Joint pain Any 30 6 20.0 7.7 38.6 30 3 10.0 2.1 26.5 118 11 9.3 4.7 16.1

Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1

Related 30 5 16.7 5.6 34.7 30 2 6.7 0.8 22.1 118 11 9.3 4.7 16.1

Muscle ache Any 30 7 23.3 9.9 42.3 30 6 20.0 7.7 38.6 118 20 16.9 10.7 25.0 Grade 3 30 2 6.7 0.8 22.1 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1

Related 30 7 23.3 9.9 42.3 30 4 13.3 3.8 30.7 118 18 15.3 9.3 23.0

Shivering (Chills) Any 30 3 10.0 2.1 26.5 30 2 6.7 0.8 22.1 118 6 5.1 1.9 10.7 Grade 3 30 1 3.3 0.1 17.2 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1

Related 30 3 10.0 2.1 26.5 30 2 6.7 0.8 22.1 118 4 3.4 0.9 8.5

Fever ≥38.0°C 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2 118 0 0.0 0.0 3.1

≥39.0°C 30 0 0.0 0.0 11.6 30 0 0.0 0.0 11.6 118 0 0.0 0.0 3.1 Related 30 2 6.7 0.8 22.1 30 1 3.3 0.1 17.2 118 0 0.0 0.0 3.1

N = number of subjects with at least one documented dose n/% = number/percentage of subjects reporting the symptom at least once 95% CI = exact 95% confidence interval; LL = Lower Limit; UL = Upper Limit Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 = general symptoms that prevented normal activities. Related = general symptom assessed by the investigator as causally related to the vaccination.

*Gastrointestinal symptoms included nausea, vomiting, diarrhoea and /or abdominal pain

Secondary Outcome Variable(s): Number (%) of subjects reporting the occurrence of pIMDs during the entire study period (Day 0 to Day 546) (Total Vaccinated cohort) pIMDs Q-PAN-

1A Group N = 61

Q-PAN-1B Group N = 60

Q-PAN-1C Group N = 60

Q-PAN-1D Group N = 61

Q-PAN-2 Group N = 60

Placebo Group

N = 118

Subjects with any pIMD(s), n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Subjects with related pIMD(s), n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Secondary Outcome Variable(s): Number (%) of subjects reporting pregnancies and their outcomes during the entire study period (Day 0 to Day 546) (Total Vaccinated cohort)

Q-PAN-1A Group N = 61

Q-PAN-1B Group N = 60

Q-PAN-1C Group N = 60

Q-PAN-1D Group N = 61

Q-PAN-2 Group N = 60

Placebo Group

N = 118

Categories n % n % n % n % n % n %

Subjects with related pregnancies - - - - - - - - 0 0.0 - -

Live infant NO apparent congenital anomaly 0 0.0 0 0.0 0 0.0 1 1.6 1 1.6 0 0.0

Spontaneous abortion, No apparent congenital anomaly (<22wk)

0 0.0 0 0.0 0 0.0 0 0.0 1 1.6 0 0.0

Lost to follow up 0 0.0 0 0.0 0 0.0 0 0.0 1 1.6 0 0.0

- = Not Applicable N = number of pregnancies n = number of in a given category % = n / Number of with available results x100 Secondary Outcome Variable(s): Number (%) of subjects reporting the occurrence of MAEs during the entire study period (Day 0 to Day 546) (Total Vaccinated cohort)

MAEs occurring from Day 0 to Day 546 following vaccination

Q-PAN-1A Group 1$ N = 31

Q-PAN-1B Group 1#

N = 30

Q-PAN-1C Group 1#

N = 30

Q-PAN-1D Group 1#

N = 30

Q-PAN-2 Group 1#

N = 30 Subjects with any MAE(s), n (%) 13 (41.9) 22 (73.3) 13 (43.3) 19 (63.3) 20 (66.7)

Subjects with related MAE(s), n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Sinusitis 4 (12.9) 4 (13.3) 3 (10.0) 6 (20.0) 6 (20.0) Bronchitis 2 (6.5) - - 4 (13.3) 2 (6.7)

Upper respiratory tract infection - 3 (10.0) - - 2 (6.7)

Depression - 2 (6.7) 2 (6.7) - -

Ear infection 2 (6.5) - 2 (6.7) - - Tooth infection - - - - 3 (10.0)

Anaemia - - - 2 (6.7) -

Back pain - 2 (6.7) - - - Cellulitis - 2 (6.7) - - -

Hypertension - - - 2 (6.7) -

Influenza - - - - 2 (6.7)

Insomnia 2 (6.5) - - - - Laceration 2 (6.5) - - - -

Ligament sprain - 2 (6.7) - - -

Pain in extremity - - - 2 (6.7) - Toothache - 2 (6.7) - - -

Urinary tract infection - - 2 (6.7) - -

MAEs Q-PAN-1A Group 2#

N = 30

Q-PAN-1B Group 2#

N = 30

Q-PAN-1C Group 2#

N = 30

Q-PAN-1D Group 2$

N = 31

Q-PAN-2 Group 2#

N = 30

Placebo Group$ N = 118

Subjects with any MAE(s), n (%) 14 (46.7) 12 (40.0) 17 (56.7) 15 (48.4) 14 (46.7) 63 (53.4) Subjects with related MAE(s), n (%) 0 (0.0) 0 (0.0) 2 (6.7) 1 (3.2) 0 (0.0) 1 (0.8)

Sinusitis - 2 (6.7) 2 (6.7) 4 (12.9) 3 (10.0) 6 (5.1)

Bronchitis - 3 (10.0) 2 (6.7) - - 6 (5.1) Ligament sprain - - - 2 (6.5) 2 (6.7) 5 (4.2)

Procedural pain - - 2 (6.7) 2 (6.5) - 4 (3.4)

Upper respiratory tract infection - 2 (6.7) - - - 4 (3.4) Cystitis - - - - - 4 (3.4)

Conjunctivitis - - - - 2 (6.7) -

Dyspnoea - - - 2 (6.5) - -

Hypertension - - - - 2 (6.7) - Influenza like illness - - - 2 (6.5) - -

Insomnia - - - - 2 (6.7) -

-: Implies that adverse event was not reported in the particular group or that the adverse event was reported in the particular group but did not fall within the pre-defined counting rule for that group. Detail of rule in studies with mixed groups: $As there were >30 subjects per treatment group and >3 groups, only the 5 most frequent events in each treatment group were listed.

#As there were ≤30 subjects per treatment group, any AE that occurred in more than 1 subject in any group were listed.

Secondary Outcome Variable(s): Number (%) of subjects reporting the occurrence of AESIs during the entire study period (Day 0 to Day 546) (Total Vaccinated cohort)

AESIs Q-PAN-1A Group 1 N = 31

Q-PAN-1B Group 1 N = 30

Q-PAN-1C Group 1 N = 30

Q-PAN-1D Group 1 N = 30

Q-PAN-2 Group 1 N = 30

Q-PAN-1A Group 2 N = 30

Q-PAN-1B Group 2 N = 30

Q-PAN-1C Group

2 N = 30

Q-PAN-1D Group 2 N = 31

Q-PAN-2 Group 2 N = 30

Placebo Group N = 118

Subjects with any AESI(s), n (%)

0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (1.7)

Subjects with related AESI(s), n (%)

0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

Lip oedema 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.8)

Urticaria 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.8) Secondary Outcome Variable(s): Distribution of haematology and biochemistry with respect to normal laboratory ranges up to day 385. (Total Vaccinated cohort)

Q-PAN-1A Group 1 N = 31

Q-PAN-1B Group 1 N = 30

Q-PAN-1C Group 1 N = 30

Unknown

Below Within Above Unknown

Below Within Above Unknown

Below Within Above

Laboratory parameter

Timing N n % n % n % n % N n % n % n % n % N n % n % n % n %

Alanine Aminotransferase

PRE 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 27 90.0 3 10.0

PI(D7) 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 28 93.3 2 6.7

PI(D21) 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3 PII(D28) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D42) 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 27 90.0 3 10.0 30 0 0.0 0 0.0 28 93.3 2 6.7

PII(D182) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 27 93.1 2 6.9 29 0 0.0 0 0.0 27 93.1 2 6.9 PIII(D191) 29 0 0.0 0 0.0 28 96.6 1 3.4 29 0 0.0 0 0.0 26 89.7 3 10.3 28 0 0.0 0 0.0 24 85.7 4 14.3

PIII(D385) 27 0 0.0 0 0.0 27 100 0 0.0 29 1 3.4 0 0.0 24 82.8 4 13.8 23 0 0.0 0 0.0 21 91.3 2 8.7

Alkaline Phosphatase

PRE 31 0 0.0 0 0.0 29 93.5 2 6.5 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 30 100 0 0.0 PI(D7) 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 29 96.7 1 3.3

PI(D21) 31 0 0.0 0 0.0 29 93.5 2 6.5 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 30 100 0 0.0

PII(D28) 30 0 0.0 0 0.0 28 93.3 2 6.7 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D42) 31 0 0.0 0 0.0 29 93.5 2 6.5 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 30 100 0 0.0 PII(D182) 30 0 0.0 0 0.0 28 93.3 2 6.7 29 0 0.0 0 0.0 27 93.1 2 6.9 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D191) 29 0 0.0 0 0.0 27 93.1 2 6.9 29 0 0.0 0 0.0 27 93.1 2 6.9 28 0 0.0 0 0.0 28 100 0 0.0

PIII(D385) 27 0 0.0 0 0.0 25 92.6 2 7.4 29 1 3.4 0 0.0 27 93.1 1 3.4 23 0 0.0 0 0.0 23 100 0 0.0 Aspartate Aminotransferase

PRE 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3

PI(D7) 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 28 93.3 2 6.7

PI(D21) 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D28) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 0 0.0 29 96.7 1 3.3 PII(D42) 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D182) 30 0 0.0 0 0.0 28 93.3 2 6.7 29 0 0.0 0 0.0 28 96.6 1 3.4 29 1 3.4 0 0.0 28 96.6 0 0.0

PIII(D191) 29 0 0.0 0 0.0 28 96.6 1 3.4 29 0 0.0 0 0.0 27 93.1 2 6.9 28 0 0.0 0 0.0 26 92.9 2 7.1 PIII(D385) 27 0 0.0 0 0.0 25 92.6 2 7.4 29 1 3.4 0 0.0 27 93.1 1 3.4 23 0 0.0 0 0.0 23 100 0 0.0

total Bilirubin

PRE 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 30 100 0 0.0

PI(D7) 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 PI(D21) 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PII(D28) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 30 100 0 0.0

PII(D42) 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PII(D182) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 29 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D191) 29 0 0.0 0 0.0 28 96.6 1 3.4 29 0 0.0 0 0.0 29 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 PIII(D385) 27 0 0.0 0 0.0 26 96.3 1 3.7 29 1 3.4 0 0.0 28 96.6 0 0.0 23 0 0.0 0 0.0 23 100 0 0.0

Bilirubin Conjugated / Direct

PRE 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PI(D7) 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PI(D21) 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 PII(D28) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PII(D42) 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PII(D182) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 PIII(D191) 29 0 0.0 0 0.0 29 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0

PIII(D385) 27 0 0.0 0 0.0 27 100 0 0.0 29 1 3.4 0 0.0 28 96.6 0 0.0 23 0 0.0 0 0.0 23 100 0 0.0

Creatinine PRE 31 0 0.0 1 3.2 30 96.8 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0 PI(D7) 31 0 0.0 4 12.9 26 83.9 1 3.2 30 0 0.0 3 10.0 27 90.0 0 0.0 30 0 0.0 4 13.3 24 80.0 2 6.7

PI(D21) 31 0 0.0 4 12.9 27 87.1 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0 30 0 0.0 2 6.7 27 90.0 1 3.3

PII(D28) 30 0 0.0 5 16.7 25 83.3 0 0.0 29 0 0.0 3 10.3 26 89.7 0 0.0 30 0 0.0 3 10.0 26 86.7 1 3.3

PII(D42) 31 0 0.0 3 9.7 28 90.3 0 0.0 30 0 0.0 2 6.7 27 90.0 1 3.3 30 0 0.0 2 6.7 26 86.7 2 6.7 PII(D182) 30 0 0.0 4 13.3 26 86.7 0 0.0 29 0 0.0 1 3.4 28 96.6 0 0.0 29 0 0.0 6 20.7 23 79.3 0 0.0

PIII(D191) 29 0 0.0 2 6.9 27 93.1 0 0.0 29 0 0.0 3 10.3 26 89.7 0 0.0 28 0 0.0 4 14.3 24 85.7 0 0.0

PIII(D385) 27 0 0.0 5 18.5 22 81.5 0 0.0 29 1 3.4 2 6.9 26 89.7 0 0.0 23 0 0.0 1 4.3 22 95.7 0 0.0 Eosinophils

PRE 31 0 0.0 7 22.6 24 77.4 0 0.0 30 0 0.0 5 16.7 24 80.0 1 3.3 30 1 3.3 10 33.3 18 60.0 1 3.3

PI(D7) 31 2 6.5 5 16.1 24 77.4 0 0.0 30 1 3.3 7 23.3 21 70.0 1 3.3 30 2 6.7 7 23.3 20 66.7 1 3.3

PI(D21) 31 1 3.2 6 19.4 24 77.4 0 0.0 30 0 0.0 5 16.7 24 80.0 1 3.3 30 2 6.7 6 20.0 19 63.3 3 10.0

PII(D28) 30 0 0.0 8 26.7 22 73.3 0 0.0 29 0 0.0 4 13.8 23 79.3 2 6.9 30 0 0.0 7 23.3 21 70.0 2 6.7 PII(D42) 31 0 0.0 3 9.7 28 90.3 0 0.0 30 0 0.0 5 16.7 24 80.0 1 3.3 30 0 0.0 6 20.0 22 73.3 2 6.7

PII(D182) 30 0 0.0 4 13.3 26 86.7 0 0.0 29 0 0.0 3 10.3 24 82.8 2 6.9 29 0 0.0 6 20.7 23 79.3 0 0.0

PIII(D191) 29 0 0.0 2 6.9 27 93.1 0 0.0 29 0 0.0 1 3.4 27 93.1 1 3.4 28 0 0.0 4 14.3 22 78.6 2 7.1 PIII(D385) 27 0 0.0 2 7.4 25 92.6 0 0.0 29 1 3.4 4 13.8 23 79.3 1 3.4 23 0 0.0 4 17.4 19 82.6 0 0.0

Hematocrit

PRE 31 0 0.0 1 3.2 26 83.9 4 12.9 30 0 0.0 0 0.0 29 96.7 1 3.3 30 1 3.3 2 6.7 26 86.7 1 3.3

PI(D7) 31 2 6.5 1 3.2 25 80.6 3 9.7 30 1 3.3 2 6.7 27 90.0 0 0.0 30 2 6.7 3 10.0 24 80.0 1 3.3 PI(D21) 31 1 3.2 3 9.7 26 83.9 1 3.2 30 0 0.0 4 13.3 24 80.0 2 6.7 30 2 6.7 3 10.0 25 83.3 0 0.0

PII(D28) 30 0 0.0 3 10.0 26 86.7 1 3.3 29 0 0.0 4 13.8 25 86.2 0 0.0 30 0 0.0 3 10.0 26 86.7 1 3.3

PII(D42) 31 0 0.0 2 6.5 28 90.3 1 3.2 30 0 0.0 3 10.0 26 86.7 1 3.3 30 0 0.0 4 13.3 26 86.7 0 0.0

PII(D182) 30 0 0.0 3 10.0 26 86.7 1 3.3 29 0 0.0 4 13.8 25 86.2 0 0.0 29 0 0.0 2 6.9 25 86.2 2 6.9 PIII(D191) 29 0 0.0 1 3.4 27 93.1 1 3.4 29 0 0.0 4 13.8 25 86.2 0 0.0 28 0 0.0 1 3.6 26 92.9 1 3.6

PIII(D385) 27 0 0.0 1 3.7 23 85.2 3 11.1 29 1 3.4 5 17.2 20 69.0 3 10.3 23 0 0.0 2 8.7 18 78.3 3 13.0

Hemoglobin

PRE 31 0 0.0 3 9.7 27 87.1 1 3.2 30 0 0.0 4 13.3 26 86.7 0 0.0 30 1 3.3 4 13.3 25 83.3 0 0.0 PI(D7) 31 2 6.5 4 12.9 25 80.6 0 0.0 30 1 3.3 6 20.0 23 76.7 0 0.0 30 2 6.7 7 23.3 21 70.0 0 0.0

PI(D21) 31 1 3.2 4 12.9 26 83.9 0 0.0 30 0 0.0 8 26.7 22 73.3 0 0.0 30 2 6.7 8 26.7 20 66.7 0 0.0

PII(D28) 30 0 0.0 3 10.0 27 90.0 0 0.0 29 0 0.0 7 24.1 22 75.9 0 0.0 30 0 0.0 5 16.7 25 83.3 0 0.0 PII(D42) 31 0 0.0 5 16.1 26 83.9 0 0.0 30 0 0.0 5 16.7 25 83.3 0 0.0 30 0 0.0 9 30.0 21 70.0 0 0.0

PII(D182) 30 0 0.0 4 13.3 26 86.7 0 0.0 29 0 0.0 8 27.6 21 72.4 0 0.0 29 0 0.0 7 24.1 22 75.9 0 0.0

PIII(D191) 29 0 0.0 4 13.8 25 86.2 0 0.0 29 0 0.0 7 24.1 22 75.9 0 0.0 28 0 0.0 5 17.9 23 82.1 0 0.0

PIII(D385) 27 0 0.0 2 7.4 25 92.6 0 0.0 29 1 3.4 10

34.5 18 62.1 0 0.0 23 0 0.0 5 21.7 18 78.3 0 0.0

Lymphocytes

PRE 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 1 3.3 0 0.0 29 96.7 0 0.0

PI(D7) 31 2 6.5 2 6.5 27 87.1 0 0.0 30 1 3.3 0 0.0 29 96.7 0 0.0 30 2 6.7 1 3.3 27 90.0 0 0.0 PI(D21) 31 1 3.2 0 0.0 30 96.8 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 2 6.7 2 6.7 26 86.7 0 0.0

PII(D28) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 1 3.3 28 93.3 1 3.3

PII(D42) 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 PII(D182) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 29 0 0.0 1 3.4 28 96.6 0 0.0

PIII(D191) 29 0 0.0 0 0.0 29 100 0 0.0 29 0 0.0 1 3.4 28 96.6 0 0.0 28 0 0.0 1 3.6 27 96.4 0 0.0

PIII(D385) 27 0 0.0 2 7.4 25 92.6 0 0.0 29 1 3.4 0 0.0 28 96.6 0 0.0 23 0 0.0 2 8.7 21 91.3 0 0.0

Monocytes

PRE 31 0 0.0 2 6.5 29 93.5 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0 30 1 3.3 3 10.0 26 86.7 0 0.0 PI(D7) 31 2 6.5 7 22.6 22 71.0 0 0.0 30 1 3.3 3 10.0 26 86.7 0 0.0 30 2 6.7 5 16.7 23 76.7 0 0.0

PI(D21) 31 1 3.2 3 9.7 27 87.1 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 30 2 6.7 1 3.3 27 90.0 0 0.0

PII(D28) 30 0 0.0 4 13.3 26 86.7 0 0.0 29 0 0.0 3 10.3 26 89.7 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0

PII(D42) 31 0 0.0 3 9.7 28 90.3 0 0.0 30 0 0.0 4 13.3 26 86.7 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0

PII(D182) 30 0 0.0 1 3.3 29 96.7 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 PIII(D191) 29 0 0.0 2 6.9 27 93.1 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 28 0 0.0 3 10.7 25 89.3 0 0.0

PIII(D385) 27 0 0.0 3 11.1 24 88.9 0 0.0 29 1 3.4 1 3.4 27 93.1 0 0.0 23 0 0.0 3 13.0 20 87.0 0 0.0

Neutrophils

PRE 31 0 0.0 1 3.2 29 93.5 1 3.2 30 0 0.0 0 0.0 29 96.7 1 3.3 30 1 3.3 1 3.3 25 83.3 3 10.0

PI(D7) 31 2 6.5 0 0.0 28 90.3 1 3.2 30 1 3.3 1 3.3 28 93.3 0 0.0 30 2 6.7 1 3.3 25 83.3 2 6.7 PI(D21) 31 1 3.2 2 6.5 28 90.3 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0 30 2 6.7 0 0.0 27 90.0 1 3.3

PII(D28) 30 0 0.0 1 3.3 28 93.3 1 3.3 29 0 0.0 1 3.4 28 96.6 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D42) 31 0 0.0 2 6.5 28 90.3 1 3.2 30 0 0.0 1 3.3 29 96.7 0 0.0 30 0 0.0 0 0.0 28 93.3 2 6.7 PII(D182) 30 0 0.0 0 0.0 26 86.7 4 13.3 29 0 0.0 0 0.0 28 96.6 1 3.4 29 0 0.0 1 3.4 27 93.1 1 3.4

PIII(D191) 29 0 0.0 1 3.4 27 93.1 1 3.4 29 0 0.0 0 0.0 28 96.6 1 3.4 28 0 0.0 0 0.0 25 89.3 3 10.7

PIII(D385) 27 0 0.0 1 3.7 24 88.9 2 7.4 29 1 3.4 1 3.4 27 93.1 0 0.0 23 0 0.0 1 4.3 21 91.3 1 4.3 Platelets PRE 31 0 0.0 1 3.2 29 93.5 1 3.2 30 0 0.0 0 0.0 30 100 0 0.0 30 1 3.3 0 0.0 29 96.7 0 0.0

PI(D7) 31 2 6.5 0 0.0 28 90.3 1 3.2 30 1 3.3 0 0.0 29 96.7 0 0.0 30 2 6.7 0 0.0 28 93.3 0 0.0

PI(D21) 31 1 3.2 0 0.0 29 93.5 1 3.2 30 0 0.0 0 0.0 30 100 0 0.0 30 2 6.7 0 0.0 28 93.3 0 0.0

PII(D28) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 PII(D42) 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 30 100 0 0.0 30 1 3.3 0 0.0 29 96.7 0 0.0

PII(D182) 30 0 0.0 1 3.3 28 93.3 1 3.3 29 0 0.0 0 0.0 28 96.6 1 3.4 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D191) 29 0 0.0 1 3.4 27 93.1 1 3.4 29 0 0.0 0 0.0 29 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 PIII(D385) 27 0 0.0 1 3.7 26 96.3 0 0.0 29 1 3.4 0 0.0 28 96.6 0 0.0 23 0 0.0 0 0.0 23 100 0 0.0

Erythrocytes (Red Blood Cells)

PRE 31 0 0.0 1 3.2 30 96.8 0 0.0 30 0 0.0 4 13.3 26 86.7 0 0.0 30 1 3.3 4 13.3 25 83.3 0 0.0

PI(D7) 31 2 6.5 1 3.2 28 90.3 0 0.0 30 1 3.3 2 6.7 27 90.0 0 0.0 30 2 6.7 8 26.7 20 66.7 0 0.0

PI(D21) 31 1 3.2 3 9.7 27 87.1 0 0.0 30 0 0.0 6 20.0 24 80.0 0 0.0 30 2 6.7 5 16.7 23 76.7 0 0.0 PII(D28) 30 0 0.0 2 6.7 28 93.3 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 30 0 0.0 4 13.3 26 86.7 0 0.0

PII(D42) 31 0 0.0 4 12.9 27 87.1 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 30 0 0.0 7 23.3 23 76.7 0 0.0

PII(D182) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 4 13.8 25 86.2 0 0.0 29 0 0.0 3 10.3 25 86.2 1 3.4 PIII(D191) 29 0 0.0 2 6.9 27 93.1 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 28 0 0.0 2 7.1 26 92.9 0 0.0

PIII(D385) 27 0 0.0 1 3.7 26 96.3 0 0.0 29 1 3.4 3 10.3 25 86.2 0 0.0 23 0 0.0 2 8.7 21 91.3 0 0.0

Urea Nitrogen

PRE 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3 PI(D7) 31 0 0.0 1 3.2 30 96.8 0 0.0 30 0 0.0 0 0.0 27 90.0 3 10.0 30 0 0.0 1 3.3 28 93.3 1 3.3

PI(D21) 31 0 0.0 2 6.5 29 93.5 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 1 3.3 28 93.3 1 3.3

PII(D28) 30 0 0.0 2 6.7 27 90.0 1 3.3 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 0 0.0 30 100 0 0.0

PII(D42) 31 0 0.0 1 3.2 30 96.8 0 0.0 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 30 100 0 0.0 PII(D182) 30 0 0.0 1 3.3 29 96.7 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 29 0 0.0 1 3.4 28 96.6 0 0.0

PIII(D191) 29 0 0.0 1 3.4 28 96.6 0 0.0 29 0 0.0 0 0.0 28 96.6 1 3.4 28 0 0.0 0 0.0 28 100 0 0.0

PIII(D385) 27 0 0.0 2 7.4 25 92.6 0 0.0 29 1 3.4 0 0.0 27 93.1 1 3.4 23 0 0.0 0 0.0 23 100 0 0.0 Leukocytes (White Blood Cells)

PRE 31 0 0.0 3 9.7 27 87.1 1 3.2 30 0 0.0 0 0.0 29 96.7 1 3.3 30 1 3.3 1 3.3 25 83.3 3 10.0

PI(D7) 31 2 6.5 1 3.2 27 87.1 1 3.2 30 1 3.3 1 3.3 28 93.3 0 0.0 30 2 6.7 0 0.0 25 83.3 3 10.0

PI(D21) 31 1 3.2 1 3.2 29 93.5 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0 30 2 6.7 0 0.0 27 90.0 1 3.3 PII(D28) 30 0 0.0 2 6.7 27 90.0 1 3.3 29 0 0.0 2 6.9 27 93.1 0 0.0 30 0 0.0 1 3.3 28 93.3 1 3.3

PII(D42) 31 0 0.0 3 9.7 28 90.3 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 30 0 0.0 0 0.0 27 90.0 3 10.0

PII(D182) 30 0 0.0 0 0.0 27 90.0 3 10.0 29 0 0.0 0 0.0 28 96.6 1 3.4 29 0 0.0 2 6.9 26 89.7 1 3.4

PIII(D191) 29 0 0.0 1 3.4 27 93.1 1 3.4 29 0 0.0 0 0.0 28 96.6 1 3.4 28 0 0.0 1 3.6 22 78.6 5 17.9 PIII(D385) 27 0 0.0 2 7.4 24 88.9 1 3.7 29 1 3.4 3 10.3 24 82.8 1 3.4 23 0 0.0 2 8.7 20 87.0 1 4.3

Q-PAN-1D Group 1 N = 30

Q-PAN-2 Group 1 N = 30

Unknown Below Within Above Unknown Below Within Above

Laboratory parameter Timing N n % n % n % n % N n % n % n % n %

Alanine Aminotransferase PRE 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 30 100 0 0.0

PI(D7) 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 30 100 0 0.0 PI(D21) 29 0 0.0 0 0.0 25 86.2 4 13.8 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D28) 29 0 0.0 0 0.0 26 89.7 3 10.3 30 0 0.0 0 0.0 30 100 0 0.0

PII(D42) 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 0 0.0 29 96.7 1 3.3 PII(D182) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 28 96.6 1 3.4

PIII(D191) 28 0 0.0 0 0.0 27 96.4 1 3.6 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D385) 25 0 0.0 0 0.0 24 96.0 1 4.0 28 2 7.1 0 0.0 26 92.9 0 0.0

Alkaline Phosphatase PRE 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 28 93.3 2 6.7

PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 28 93.3 2 6.7 PI(D21) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 28 93.3 2 6.7

PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 28 93.3 2 6.7

PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 27 90.0 3 10.0

PII(D182) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 29 100 0 0.0 PIII(D191) 28 0 0.0 0 0.0 28 100 0 0.0 29 0 0.0 0 0.0 28 96.6 1 3.4

PIII(D385) 25 0 0.0 0 0.0 25 100 0 0.0 28 2 7.1 0 0.0 26 92.9 0 0.0

Aspartate Aminotransferase PRE 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 30 100 0 0.0 PI(D7) 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 30 100 0 0.0

PI(D21) 29 0 0.0 0 0.0 25 86.2 4 13.8 30 0 0.0 0 0.0 30 100 0 0.0

PII(D28) 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 0 0.0 30 100 0 0.0 PII(D42) 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D182) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D191) 28 0 0.0 0 0.0 27 96.4 1 3.6 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D385) 25 0 0.0 0 0.0 25 100 0 0.0 28 2 7.1 0 0.0 26 92.9 0 0.0 total Bilirubin PRE 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PI(D21) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 29 96.7 1 3.3 PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PII(D182) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D191) 28 0 0.0 0 0.0 28 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 PIII(D385) 25 0 0.0 0 0.0 25 100 0 0.0 28 2 7.1 0 0.0 26 92.9 0 0.0

Bilirubin Conjugated / Direct PRE 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 PI(D21) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 PII(D182) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D191) 28 0 0.0 0 0.0 28 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D385) 25 0 0.0 0 0.0 25 100 0 0.0 28 2 7.1 0 0.0 26 92.9 0 0.0

Creatinine PRE 30 0 0.0 4 13.3 26 86.7 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 PI(D7) 30 0 0.0 5 16.7 25 83.3 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0

PI(D21) 29 0 0.0 3 10.3 26 89.7 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0

PII(D28) 29 0 0.0 5 17.2 24 82.8 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 PII(D42) 29 0 0.0 3 10.3 26 89.7 0 0.0 30 0 0.0 4 13.3 26 86.7 0 0.0

PII(D182) 30 0 0.0 3 10.0 27 90.0 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0

PIII(D191) 28 0 0.0 4 14.3 24 85.7 0 0.0 29 0 0.0 4 13.8 25 86.2 0 0.0 PIII(D385) 25 0 0.0 3 12.0 22 88.0 0 0.0 28 2 7.1 2 7.1 24 85.7 0 0.0

Eosinophils PRE 30 0 0.0 7 23.3 23 76.7 0 0.0 30 0 0.0 9 30.0 21 70.0 0 0.0

PI(D7) 30 1 3.3 6 20.0 23 76.7 0 0.0 30 0 0.0 9 30.0 21 70.0 0 0.0

PI(D21) 29 1 3.4 7 24.1 21 72.4 0 0.0 30 0 0.0 7 23.3 23 76.7 0 0.0 PII(D28) 29 0 0.0 4 13.8 25 86.2 0 0.0 30 0 0.0 7 23.3 22 73.3 1 3.3

PII(D42) 29 0 0.0 3 10.3 26 89.7 0 0.0 30 0 0.0 6 20.0 24 80.0 0 0.0

PII(D182) 30 0 0.0 6 20.0 24 80.0 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 PIII(D191) 28 0 0.0 3 10.7 25 89.3 0 0.0 29 0 0.0 4 13.8 25 86.2 0 0.0

PIII(D385) 25 0 0.0 8 32.0 17 68.0 0 0.0 28 1 3.6 5 17.9 22 78.6 0 0.0

Hematocrit PRE 30 0 0.0 2 6.7 25 83.3 3 10.0 30 0 0.0 1 3.3 27 90.0 2 6.7

PI(D7) 30 1 3.3 3 10.0 25 83.3 1 3.3 30 0 0.0 2 6.7 27 90.0 1 3.3 PI(D21) 29 1 3.4 4 13.8 23 79.3 1 3.4 30 0 0.0 4 13.3 25 83.3 1 3.3

PII(D28) 29 0 0.0 2 6.9 26 89.7 1 3.4 30 0 0.0 3 10.0 26 86.7 1 3.3

PII(D42) 29 0 0.0 3 10.3 25 86.2 1 3.4 30 0 0.0 4 13.3 25 83.3 1 3.3 PII(D182) 30 0 0.0 2 6.7 28 93.3 0 0.0 29 0 0.0 1 3.4 26 89.7 2 6.9

PIII(D191) 28 0 0.0 4 14.3 23 82.1 1 3.6 29 0 0.0 2 6.9 26 89.7 1 3.4

PIII(D385) 25 0 0.0 1 4.0 23 92.0 1 4.0 28 1 3.6 1 3.6 25 89.3 1 3.6

Hemoglobin PRE 30 0 0.0 5 16.7 25 83.3 0 0.0 30 0 0.0 3 10.0 26 86.7 1 3.3

PI(D7) 30 1 3.3 4 13.3 25 83.3 0 0.0 30 0 0.0 5 16.7 25 83.3 0 0.0 PI(D21) 29 1 3.4 4 13.8 24 82.8 0 0.0 30 0 0.0 7 23.3 23 76.7 0 0.0

PII(D28) 29 0 0.0 5 17.2 24 82.8 0 0.0 30 0 0.0 7 23.3 23 76.7 0 0.0

PII(D42) 29 0 0.0 5 17.2 24 82.8 0 0.0 30 0 0.0 9 30.0 21 70.0 0 0.0

PII(D182) 30 0 0.0 3 10.0 27 90.0 0 0.0 29 0 0.0 4 13.8 25 86.2 0 0.0 PIII(D191) 28 0 0.0 4 14.3 24 85.7 0 0.0 29 0 0.0 4 13.8 25 86.2 0 0.0

PIII(D385) 25 0 0.0 6 24.0 19 76.0 0 0.0 28 1 3.6 5 17.9 22 78.6 0 0.0

Lymphocytes PRE 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3 PI(D7) 30 1 3.3 0 0.0 29 96.7 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3

PI(D21) 29 1 3.4 0 0.0 28 96.6 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PII(D182) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D191) 28 0 0.0 0 0.0 28 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D385) 25 0 0.0 0 0.0 25 100 0 0.0 28 1 3.6 1 3.6 25 89.3 1 3.6 Monocytes PRE 30 0 0.0 4 13.3 26 86.7 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0

PI(D7) 30 1 3.3 3 10.0 26 86.7 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0

PI(D21) 29 1 3.4 3 10.3 25 86.2 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 PII(D28) 29 0 0.0 3 10.3 26 89.7 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0

PII(D42) 29 0 0.0 5 17.2 24 82.8 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0

PII(D182) 30 0 0.0 4 13.3 26 86.7 0 0.0 29 0 0.0 3 10.3 26 89.7 0 0.0

PIII(D191) 28 0 0.0 3 10.7 25 89.3 0 0.0 29 0 0.0 3 10.3 26 89.7 0 0.0 PIII(D385) 25 0 0.0 4 16.0 21 84.0 0 0.0 28 1 3.6 6 21.4 21 75.0 0 0.0

Neutrophils PRE 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 28 93.3 2 6.7

PI(D7) 30 1 3.3 0 0.0 29 96.7 0 0.0 30 0 0.0 0 0.0 28 93.3 2 6.7 PI(D21) 29 1 3.4 0 0.0 27 93.1 1 3.4 30 0 0.0 0 0.0 30 100 0 0.0

PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0

PII(D42) 29 0 0.0 1 3.4 28 96.6 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0 PII(D182) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 28 96.6 1 3.4

PIII(D191) 28 0 0.0 1 3.6 26 92.9 1 3.6 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D385) 25 0 0.0 0 0.0 24 96.0 1 4.0 28 1 3.6 0 0.0 27 96.4 0 0.0

Platelets PRE 30 0 0.0 1 3.3 27 90.0 2 6.7 30 0 0.0 2 6.7 28 93.3 0 0.0 PI(D7) 30 1 3.3 2 6.7 25 83.3 2 6.7 30 0 0.0 2 6.7 28 93.3 0 0.0

PI(D21) 29 1 3.4 2 6.9 25 86.2 1 3.4 30 0 0.0 1 3.3 29 96.7 0 0.0

PII(D28) 29 0 0.0 1 3.4 26 89.7 2 6.9 30 0 0.0 2 6.7 28 93.3 0 0.0 PII(D42) 29 0 0.0 1 3.4 27 93.1 1 3.4 30 0 0.0 2 6.7 28 93.3 0 0.0

PII(D182) 30 0 0.0 1 3.3 28 93.3 1 3.3 29 0 0.0 2 6.9 27 93.1 0 0.0

PIII(D191) 28 0 0.0 1 3.6 26 92.9 1 3.6 29 0 0.0 2 6.9 26 89.7 1 3.4 PIII(D385) 25 0 0.0 0 0.0 24 96.0 1 4.0 28 1 3.6 2 7.1 25 89.3 0 0.0

Erythrocytes (Red Blood Cells) PRE 30 0 0.0 1 3.3 29 96.7 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0

PI(D7) 30 1 3.3 3 10.0 26 86.7 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0

PI(D21) 29 1 3.4 3 10.3 25 86.2 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0 PII(D28) 29 0 0.0 3 10.3 26 89.7 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0

PII(D42) 29 0 0.0 4 13.8 25 86.2 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0

PII(D182) 30 0 0.0 2 6.7 28 93.3 0 0.0 29 0 0.0 1 3.4 28 96.6 0 0.0 PIII(D191) 28 0 0.0 3 10.7 25 89.3 0 0.0 29 0 0.0 1 3.4 28 96.6 0 0.0

PIII(D385) 25 0 0.0 1 4.0 24 96.0 0 0.0 28 1 3.6 1 3.6 26 92.9 0 0.0

Urea Nitrogen PRE 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 30 100 0 0.0

PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 PI(D21) 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 0 0.0 30 100 0 0.0

PII(D28) 29 0 0.0 1 3.4 27 93.1 1 3.4 30 0 0.0 0 0.0 30 100 0 0.0

PII(D42) 29 0 0.0 1 3.4 27 93.1 1 3.4 30 0 0.0 0 0.0 30 100 0 0.0 PII(D182) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D191) 28 0 0.0 0 0.0 28 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PIII(D385) 25 0 0.0 0 0.0 24 96.0 1 4.0 28 2 7.1 0 0.0 26 92.9 0 0.0

Leukocytes (White Blood Cells) PRE 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 28 93.3 2 6.7

PI(D7) 30 1 3.3 0 0.0 28 93.3 1 3.3 30 0 0.0 0 0.0 27 90.0 3 10.0 PI(D21) 29 1 3.4 0 0.0 28 96.6 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D42) 29 0 0.0 1 3.4 28 96.6 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3

PII(D182) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 27 93.1 2 6.9 PIII(D191) 28 0 0.0 2 7.1 24 85.7 2 7.1 29 0 0.0 0 0.0 28 96.6 1 3.4

PIII(D385) 25 0 0.0 0 0.0 24 96.0 1 4.0 28 1 3.6 1 3.6 25 89.3 1 3.6 Q-PAN-1A Group 2

N = 30 Q-PAN-1B Group 2

N = 30 Q-PAN-1C Group 2

N = 30

Unknown

Below Within Above Unknown

Below Within Above Unknown

Below Within Above

Laboratory parameter

Timing N n % n % n % n % N n % n % n % n % N n % n % n % n %

Alanine Aminotransferase

PRE 30 0 0.0 0 0.0 27 90.0 3 10.0 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 28 93.3 2 6.7

PI(D7) 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 28 96.6 1 3.4

PI(D21) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 27 90.0 3 10.0 28 0 0.0 0 0.0 27 96.4 1 3.6 PII(D28) 29 0 0.0 0 0.0 26 89.7 3 10.3 30 0 0.0 0 0.0 29 96.7 1 3.3 28 0 0.0 0 0.0 26 92.9 2 7.1

PII(D42) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 30 100 0 0.0 29 1 3.4 0 0.0 27 93.1 1 3.4

PII(D182) 25 0 0.0 0 0.0 22 88.0 3 12.0 29 0 0.0 0 0.0 27 93.1 2 6.9 27 0 0.0 0 0.0 27 100 0 0.0

PIII(D191) 25 0 0.0 0 0.0 23 92.0 2 8.0 28 0 0.0 0 0.0 26 92.9 2 7.1 27 0 0.0 0 0.0 27 100 0 0.0 PIII(D385) 25 1 4.0 0 0.0 22 88.0 2 8.0 25 1 4.0 0 0.0 24 96.0 0 0.0 27 1 3.7 0 0.0 25 92.6 1 3.7

Alkaline Phosphatase

PRE 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3

PI(D7) 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 27 93.1 2 6.9 PI(D21) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 27 90.0 3 10.0 28 0 0.0 0 0.0 27 96.4 1 3.6

PII(D28) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 29 96.7 1 3.3 28 0 0.0 0 0.0 27 96.4 1 3.6

PII(D42) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 29 96.7 1 3.3 29 1 3.4 0 0.0 27 93.1 1 3.4 PII(D182) 25 0 0.0 0 0.0 24 96.0 1 4.0 29 0 0.0 0 0.0 29 100 0 0.0 27 0 0.0 0 0.0 26 96.3 1 3.7

PIII(D191) 25 0 0.0 0 0.0 24 96.0 1 4.0 28 0 0.0 0 0.0 27 96.4 1 3.6 27 0 0.0 0 0.0 26 96.3 1 3.7

PIII(D385) 25 1 4.0 0 0.0 23 92.0 1 4.0 25 1 4.0 0 0.0 24 96.0 0 0.0 27 1 3.7 0 0.0 25 92.6 1 3.7

Aspartate Aminotransferase

PRE 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3 PI(D7) 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 28 96.6 1 3.4

PI(D21) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3 28 0 0.0 0 0.0 26 92.9 2 7.1

PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 1 3.3 0 0.0 28 93.3 1 3.3 28 0 0.0 0 0.0 28 100 0 0.0 PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3 29 1 3.4 0 0.0 27 93.1 1 3.4

PII(D182) 25 0 0.0 0 0.0 24 96.0 1 4.0 29 0 0.0 0 0.0 28 96.6 1 3.4 27 0 0.0 0 0.0 27 100 0 0.0

PIII(D191) 25 0 0.0 0 0.0 24 96.0 1 4.0 28 0 0.0 0 0.0 26 92.9 2 7.1 27 0 0.0 0 0.0 27 100 0 0.0 PIII(D385) 25 1 4.0 0 0.0 24 96.0 0 0.0 25 1 4.0 0 0.0 24 96.0 0 0.0 27 1 3.7 0 0.0 26 96.3 0 0.0

total Bilirubin

PRE 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3

PI(D7) 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PI(D21) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 PII(D28) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0

PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 29 1 3.4 0 0.0 28 96.6 0 0.0

PII(D182) 25 0 0.0 0 0.0 25 100 0 0.0 29 0 0.0 0 0.0 28 96.6 1 3.4 27 0 0.0 0 0.0 26 96.3 1 3.7 PIII(D191) 25 0 0.0 0 0.0 25 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0

PIII(D385) 25 1 4.0 0 0.0 23 92.0 1 4.0 25 1 4.0 0 0.0 24 96.0 0 0.0 27 1 3.7 0 0.0 26 96.3 0 0.0

Bilirubin Conjugated / Direct

PRE 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 PI(D21) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0

PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0

PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 29 1 3.4 0 0.0 28 96.6 0 0.0 PII(D182) 25 0 0.0 0 0.0 25 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0

PIII(D191) 25 0 0.0 0 0.0 25 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0

PIII(D385) 25 1 4.0 0 0.0 24 96.0 0 0.0 25 1 4.0 0 0.0 24 96.0 0 0.0 27 1 3.7 0 0.0 26 96.3 0 0.0

Creatinine PRE 30 0 0.0 2 6.7 27 90.0 1 3.3 30 0 0.0 7 23.3 21 70.0 2 6.7 30 0 0.0 1 3.3 27 90.0 2 6.7

PI(D7) 30 0 0.0 2 6.7 27 90.0 1 3.3 30 0 0.0 6 20.0 24 80.0 0 0.0 29 0 0.0 0 0.0 28 96.6 1 3.4 PI(D21) 29 0 0.0 3 10.3 25 86.2 1 3.4 30 0 0.0 5 16.7 24 80.0 1 3.3 28 0 0.0 0 0.0 28 100 0 0.0

PII(D28) 29 0 0.0 4 13.8 24 82.8 1 3.4 30 0 0.0 7 23.3 23 76.7 0 0.0 28 0 0.0 0 0.0 27 96.4 1 3.6

PII(D42) 29 0 0.0 3 10.3 25 86.2 1 3.4 30 0 0.0 6 20.0 24 80.0 0 0.0 29 1 3.4 1 3.4 26 89.7 1 3.4

PII(D182) 25 0 0.0 3 12.0 21 84.0 1 4.0 29 0 0.0 7 24.1 22 75.9 0 0.0 27 0 0.0 1 3.7 26 96.3 0 0.0 PIII(D191) 25 0 0.0 3 12.0 21 84.0 1 4.0 28 0 0.0 6 21.4 22 78.6 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0

PIII(D385) 25 1 4.0 3 12.0 20 80.0 1 4.0 25 1 4.0 5 20.0 19 76.0 0 0.0 27 1 3.7 1 3.7 24 88.9 1 3.7

Eosinophils

PRE 30 0 0.0 5 16.7 24 80.0 1 3.3 30 0 0.0 8 26.7 21 70.0 1 3.3 30 0 0.0 11 36.7 19 63.3 0 0.0 PI(D7) 30 0 0.0 3 10.0 27 90.0 0 0.0 30 3 10.0 6 20.0 20 66.7 1 3.3 29 1 3.4 9 31.0 19 65.5 0 0.0

PI(D21) 29 0 0.0 2 6.9 27 93.1 0 0.0 30 0 0.0 6 20.0 24 80.0 0 0.0 28 0 0.0 8 28.6 20 71.4 0 0.0

PII(D28) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 6 20.0 23 76.7 1 3.3 28 0 0.0 9 32.1 19 67.9 0 0.0 PII(D42) 29 0 0.0 1 3.4 28 96.6 0 0.0 30 0 0.0 4 13.3 25 83.3 1 3.3 29 0 0.0 8 27.6 21 72.4 0 0.0

PII(D182) 25 0 0.0 1 4.0 24 96.0 0 0.0 29 0 0.0 5 17.2 23 79.3 1 3.4 27 0 0.0 6 22.2 21 77.8 0 0.0

PIII(D191) 25 0 0.0 0 0.0 25 100 0 0.0 28 0 0.0 3 10.7 23 82.1 2 7.1 27 0 0.0 4 14.8 22 81.5 1 3.7

PIII(D385) 25 0 0.0 3 12.0 22 88.0 0 0.0 25 0 0.0 6 24.0 17 68.0 2 8.0 27 1 3.7 9 33.3 17 63.0 0 0.0 Hematocrit

PRE 30 0 0.0 1 3.3 24 80.0 5 16.7 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 0 0.0 29 96.7 1 3.3

PI(D7) 30 0 0.0 1 3.3 28 93.3 1 3.3 30 3 10.0 3 10.0 24 80.0 0 0.0 29 1 3.4 0 0.0 27 93.1 1 3.4

PI(D21) 29 0 0.0 1 3.4 27 93.1 1 3.4 30 0 0.0 1 3.3 28 93.3 1 3.3 28 0 0.0 1 3.6 27 96.4 0 0.0 PII(D28) 29 0 0.0 2 6.9 24 82.8 3 10.3 30 0 0.0 2 6.7 27 90.0 1 3.3 28 0 0.0 0 0.0 27 96.4 1 3.6

PII(D42) 29 0 0.0 1 3.4 27 93.1 1 3.4 30 0 0.0 1 3.3 29 96.7 0 0.0 29 0 0.0 1 3.4 28 96.6 0 0.0

PII(D182) 25 0 0.0 0 0.0 24 96.0 1 4.0 29 0 0.0 1 3.4 27 93.1 1 3.4 27 0 0.0 1 3.7 25 92.6 1 3.7

PIII(D191) 25 0 0.0 1 4.0 24 96.0 0 0.0 28 0 0.0 3 10.7 24 85.7 1 3.6 27 0 0.0 1 3.7 25 92.6 1 3.7 PIII(D385) 25 0 0.0 0 0.0 22 88.0 3 12.0 25 0 0.0 2 8.0 21 84.0 2 8.0 27 1 3.7 0 0.0 25 92.6 1 3.7

Hemoglobin

PRE 30 0 0.0 2 6.7 25 83.3 3 10.0 30 0 0.0 2 6.7 28 93.3 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0

PI(D7) 30 0 0.0 1 3.3 28 93.3 1 3.3 30 3 10.0 4 13.3 23 76.7 0 0.0 29 1 3.4 0 0.0 28 96.6 0 0.0 PI(D21) 29 0 0.0 2 6.9 26 89.7 1 3.4 30 0 0.0 4 13.3 25 83.3 1 3.3 28 0 0.0 3 10.7 25 89.3 0 0.0

PII(D28) 29 0 0.0 2 6.9 27 93.1 0 0.0 30 0 0.0 4 13.3 26 86.7 0 0.0 28 0 0.0 1 3.6 27 96.4 0 0.0

PII(D42) 29 0 0.0 3 10.3 26 89.7 0 0.0 30 0 0.0 4 13.3 26 86.7 0 0.0 29 0 0.0 5 17.2 24 82.8 0 0.0 PII(D182) 25 0 0.0 3 12.0 22 88.0 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 27 0 0.0 2 7.4 25 92.6 0 0.0

PIII(D191) 25 0 0.0 3 12.0 22 88.0 0 0.0 28 0 0.0 3 10.7 25 89.3 0 0.0 27 0 0.0 3 11.1 24 88.9 0 0.0

PIII(D385) 25 0 0.0 4 16.0 19 76.0 2 8.0 25 0 0.0 3 12.0 22 88.0 0 0.0 27 1 3.7 3 11.1 23 85.2 0 0.0

Lymphocytes

PRE 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 3 10.0 0 0.0 27 90.0 0 0.0 29 1 3.4 0 0.0 28 96.6 0 0.0

PI(D21) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0

PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 1 3.3 29 96.7 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PII(D182) 25 0 0.0 1 4.0 24 96.0 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0

PIII(D191) 25 0 0.0 1 4.0 24 96.0 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 27 0 0.0 1 3.7 26 96.3 0 0.0 PIII(D385) 25 0 0.0 2 8.0 23 92.0 0 0.0 25 0 0.0 0 0.0 25 100 0 0.0 27 1 3.7 1 3.7 25 92.6 0 0.0

Monocytes

PRE 30 0 0.0 4 13.3 26 86.7 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0 30 0 0.0 8 26.7 22 73.3 0 0.0

PI(D7) 30 0 0.0 3 10.0 27 90.0 0 0.0 30 3 10.0 0 0.0 27 90.0 0 0.0 29 1 3.4 5 17.2 23 79.3 0 0.0

PI(D21) 29 0 0.0 4 13.8 25 86.2 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0 28 0 0.0 7 25.0 21 75.0 0 0.0 PII(D28) 29 0 0.0 1 3.4 28 96.6 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 28 0 0.0 8 28.6 20 71.4 0 0.0

PII(D42) 29 0 0.0 2 6.9 27 93.1 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 29 0 0.0 3 10.3 26 89.7 0 0.0

PII(D182) 25 0 0.0 2 8.0 23 92.0 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 27 0 0.0 7 25.9 20 74.1 0 0.0 PIII(D191) 25 0 0.0 3 12.0 22 88.0 0 0.0 28 0 0.0 3 10.7 25 89.3 0 0.0 27 0 0.0 4 14.8 23 85.2 0 0.0

PIII(D385) 25 0 0.0 2 8.0 23 92.0 0 0.0 25 0 0.0 2 8.0 23 92.0 0 0.0 27 1 3.7 5 18.5 21 77.8 0 0.0

Neutrophils

PRE 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 2 6.7 27 90.0 1 3.3 30 0 0.0 1 3.3 29 96.7 0 0.0

PI(D7) 30 0 0.0 1 3.3 28 93.3 1 3.3 30 3 10.0 2 6.7 25 83.3 0 0.0 29 1 3.4 1 3.4 27 93.1 0 0.0 PI(D21) 29 0 0.0 2 6.9 27 93.1 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0 28 0 0.0 2 7.1 26 92.9 0 0.0

PII(D28) 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 1 3.3 29 96.7 0 0.0 28 0 0.0 3 10.7 25 89.3 0 0.0

PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 1 3.3 27 90.0 2 6.7 29 0 0.0 2 6.9 26 89.7 1 3.4 PII(D182) 25 0 0.0 0 0.0 25 100 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 27 0 0.0 2 7.4 24 88.9 1 3.7

PIII(D191) 25 0 0.0 1 4.0 22 88.0 2 8.0 28 0 0.0 2 7.1 26 92.9 0 0.0 27 0 0.0 1 3.7 26 96.3 0 0.0

PIII(D385) 25 0 0.0 0 0.0 25 100 0 0.0 25 0 0.0 3 12.0 22 88.0 0 0.0 27 1 3.7 3 11.1 23 85.2 0 0.0

Platelets PRE 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 30 1 3.3 1 3.3 28 93.3 0 0.0

PI(D7) 30 1 3.3 0 0.0 28 93.3 1 3.3 30 4 13.3 0 0.0 26 86.7 0 0.0 29 3 10.3 0 0.0 26 89.7 0 0.0 PI(D21) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 30 100 0 0.0 28 1 3.6 0 0.0 27 96.4 0 0.0

PII(D28) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0

PII(D42) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 30 100 0 0.0 29 1 3.4 0 0.0 28 96.6 0 0.0

PII(D182) 25 0 0.0 0 0.0 25 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0 PIII(D191) 25 0 0.0 0 0.0 25 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0

PIII(D385) 25 0 0.0 0 0.0 25 100 0 0.0 25 0 0.0 0 0.0 25 100 0 0.0 27 2 7.4 0 0.0 25 92.6 0 0.0

Erythrocytes (Red Blood Cells)

PRE 30 0 0.0 5 16.7 25 83.3 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 30 0 0.0 5 16.7 25 83.3 0 0.0 PI(D7) 30 0 0.0 4 13.3 26 86.7 0 0.0 30 3 10.0 2 6.7 25 83.3 0 0.0 29 1 3.4 3 10.3 25 86.2 0 0.0

PI(D21) 29 0 0.0 4 13.8 25 86.2 0 0.0 30 0 0.0 2 6.7 28 93.3 0 0.0 28 0 0.0 4 14.3 24 85.7 0 0.0

PII(D28) 29 0 0.0 3 10.3 26 89.7 0 0.0 30 0 0.0 4 13.3 26 86.7 0 0.0 28 0 0.0 5 17.9 23 82.1 0 0.0 PII(D42) 29 0 0.0 4 13.8 25 86.2 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 29 0 0.0 5 17.2 24 82.8 0 0.0

PII(D182) 25 0 0.0 1 4.0 24 96.0 0 0.0 29 0 0.0 2 6.9 26 89.7 1 3.4 27 0 0.0 2 7.4 24 88.9 1 3.7

PIII(D191) 25 0 0.0 1 4.0 24 96.0 0 0.0 28 0 0.0 2 7.1 25 89.3 1 3.6 27 0 0.0 1 3.7 26 96.3 0 0.0

PIII(D385) 25 0 0.0 1 4.0 24 96.0 0 0.0 25 0 0.0 2 8.0 23 92.0 0 0.0 27 1 3.7 1 3.7 25 92.6 0 0.0 Urea Nitrogen

PRE 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 30 100 0 0.0

PI(D7) 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0

PI(D21) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 0 0.0 28 93.3 2 6.7 28 0 0.0 0 0.0 28 100 0 0.0 PII(D28) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0

PII(D42) 29 0 0.0 0 0.0 28 96.6 1 3.4 30 0 0.0 0 0.0 29 96.7 1 3.3 29 1 3.4 0 0.0 27 93.1 1 3.4

PII(D182) 25 0 0.0 0 0.0 25 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0

PIII(D191) 25 0 0.0 0 0.0 25 100 0 0.0 28 0 0.0 0 0.0 26 92.9 2 7.1 27 0 0.0 0 0.0 26 96.3 1 3.7 PIII(D385) 25 1 4.0 0 0.0 24 96.0 0 0.0 25 1 4.0 0 0.0 23 92.0 1 4.0 27 1 3.7 1 3.7 24 88.9 1 3.7

Leukocytes (White Blood Cells)

PRE 30 0 0.0 0 0.0 28 93.3 2 6.7 30 0 0.0 2 6.7 27 90.0 1 3.3 30 0 0.0 2 6.7 27 90.0 1 3.3

PI(D7) 30 0 0.0 1 3.3 28 93.3 1 3.3 30 3 10.0 2 6.7 25 83.3 0 0.0 29 1 3.4 1 3.4 27 93.1 0 0.0 PI(D21) 29 0 0.0 2 6.9 26 89.7 1 3.4 30 0 0.0 1 3.3 29 96.7 0 0.0 28 0 0.0 2 7.1 26 92.9 0 0.0

PII(D28) 29 0 0.0 0 0.0 27 93.1 2 6.9 30 0 0.0 1 3.3 29 96.7 0 0.0 28 0 0.0 2 7.1 26 92.9 0 0.0

PII(D42) 29 0 0.0 0 0.0 29 100 0 0.0 30 0 0.0 1 3.3 27 90.0 2 6.7 29 0 0.0 1 3.4 28 96.6 0 0.0 PII(D182) 25 0 0.0 0 0.0 25 100 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 27 0 0.0 1 3.7 25 92.6 1 3.7

PIII(D191) 25 0 0.0 2 8.0 21 84.0 2 8.0 28 0 0.0 1 3.6 27 96.4 0 0.0 27 0 0.0 3 11.1 24 88.9 0 0.0

PIII(D385) 25 0 0.0 1 4.0 24 96.0 0 0.0 25 0 0.0 1 4.0 23 92.0 1 4.0 27 1 3.7 2 7.4 24 88.9 0 0.0

Q-PAN-1D Group 2 N = 31

Q-PAN-2 Group 2 N = 30

Placebo Group N = 118

Unknown

Below Within Above Unknown

Below Within Above Unknown

Below Within Above

Laboratory parameter

Timing N n % n % n % n % N n % n % n % n % N n % n % n % n %

Alanine Aminotransferase

PRE 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 28 93.3 2 6.7 118 1 0.8 0 0.0 112 94.9 5 4.2 PI(D7) 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 28 93.3 2 6.7 118 0 0.0 0 0.0 112 94.9 6 5.1

PI(D21) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 29 100 0 0.0 115 0 0.0 0 0.0 109 94.8 6 5.2

PII(D28) 30 0 0.0 0 0.0 29 96.7 1 3.3 28 0 0.0 0 0.0 27 96.4 1 3.6 116 0 0.0 0 0.0 113 97.4 3 2.6

PII(D42) 30 0 0.0 0 0.0 29 96.7 1 3.3 28 1 3.6 0 0.0 25 89.3 2 7.1 116 0 0.0 0 0.0 109 94.0 7 6.0 PII(D182) 27 1 3.7 0 0.0 24 88.9 2 7.4 27 0 0.0 0 0.0 24 88.9 3 11.1 115 1 0.9 0 0.0 106 92.2 8 7.0

PIII(D191) 27 0 0.0 0 0.0 25 92.6 2 7.4 27 0 0.0 0 0.0 24 88.9 3 11.1 115 0 0.0 0 0.0 109 94.8 6 5.2

PIII(D385) 24 0 0.0 0 0.0 24 100 0 0.0 26 0 0.0 0 0.0 25 96.2 1 3.8 111 1 0.9 0 0.0 107 96.4 3 2.7 Alkaline Phosphatase

PRE 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 29 96.7 1 3.3 118 1 0.8 0 0.0 104 88.1 13 11.0

PI(D7) 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 0 0.0 29 96.7 1 3.3 118 0 0.0 0 0.0 108 91.5 10 8.5

PI(D21) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 28 96.6 1 3.4 115 0 0.0 0 0.0 106 92.2 9 7.8

PII(D28) 30 0 0.0 0 0.0 29 96.7 1 3.3 28 0 0.0 0 0.0 27 96.4 1 3.6 116 0 0.0 0 0.0 106 91.4 10 8.6 PII(D42) 30 0 0.0 0 0.0 29 96.7 1 3.3 28 1 3.6 0 0.0 26 92.9 1 3.6 116 0 0.0 0 0.0 109 94.0 7 6.0

PII(D182) 27 1 3.7 0 0.0 26 96.3 0 0.0 27 0 0.0 0 0.0 26 96.3 1 3.7 115 1 0.9 0 0.0 108 93.9 6 5.2

PIII(D191) 27 0 0.0 0 0.0 26 96.3 1 3.7 27 0 0.0 0 0.0 26 96.3 1 3.7 115 0 0.0 0 0.0 110 95.7 5 4.3 PIII(D385) 24 0 0.0 0 0.0 24 100 0 0.0 26 0 0.0 0 0.0 25 96.2 1 3.8 111 1 0.9 0 0.0 108 97.3 2 1.8

Aspartate Aminotransferase

PRE 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 29 96.7 1 3.3 118 1 0.8 0 0.0 113 95.8 4 3.4

PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3 118 0 0.0 0 0.0 115 97.5 3 2.5 PI(D21) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 0 0.0 29 100 0 0.0 115 1 0.9 0 0.0 112 97.4 2 1.7

PII(D28) 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 116 0 0.0 0 0.0 111 95.7 5 4.3

PII(D42) 30 0 0.0 0 0.0 29 96.7 1 3.3 28 1 3.6 0 0.0 26 92.9 1 3.6 116 0 0.0 0 0.0 114 98.3 2 1.7

PII(D182) 27 1 3.7 0 0.0 24 88.9 2 7.4 27 0 0.0 0 0.0 26 96.3 1 3.7 115 1 0.9 0 0.0 109 94.8 5 4.3 PIII(D191) 27 0 0.0 0 0.0 26 96.3 1 3.7 27 0 0.0 0 0.0 26 96.3 1 3.7 115 1 0.9 0 0.0 109 94.8 5 4.3

PIII(D385) 24 0 0.0 0 0.0 23 95.8 1 4.2 26 0 0.0 0 0.0 25 96.2 1 3.8 111 1 0.9 0 0.0 110 99.1 0 0.0

total Bilirubin

PRE 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 118 1 0.8 0 0.0 116 98.3 1 0.8 PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 118 0 0.0 0 0.0 117 99.2 1 0.8

PI(D21) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 115 0 0.0 0 0.0 114 99.1 1 0.9

PII(D28) 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 116 0 0.0 0 0.0 115 99.1 1 0.9 PII(D42) 30 0 0.0 0 0.0 30 100 0 0.0 28 1 3.6 0 0.0 27 96.4 0 0.0 116 0 0.0 0 0.0 116 100 0 0.0

PII(D182) 27 1 3.7 0 0.0 26 96.3 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0 115 1 0.9 0 0.0 114 99.1 0 0.0

PIII(D191) 27 0 0.0 0 0.0 27 100 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0 115 0 0.0 0 0.0 115 100 0 0.0

PIII(D385) 24 0 0.0 0 0.0 24 100 0 0.0 26 0 0.0 0 0.0 26 100 0 0.0 111 1 0.9 0 0.0 108 97.3 2 1.8 Bilirubin Conjugated / Direct

PRE 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 118 1 0.8 0 0.0 116 98.3 1 0.8

PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 118 0 0.0 0 0.0 118 100 0 0.0

PI(D21) 30 0 0.0 0 0.0 30 100 0 0.0 29 0 0.0 0 0.0 29 100 0 0.0 115 0 0.0 0 0.0 115 100 0 0.0 PII(D28) 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 116 0 0.0 0 0.0 116 100 0 0.0

PII(D42) 30 0 0.0 0 0.0 30 100 0 0.0 28 1 3.6 0 0.0 27 96.4 0 0.0 116 0 0.0 0 0.0 116 100 0 0.0

PII(D182) 27 1 3.7 0 0.0 26 96.3 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0 115 1 0.9 0 0.0 114 99.1 0 0.0

PIII(D191) 27 0 0.0 0 0.0 27 100 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0 115 0 0.0 0 0.0 115 100 0 0.0 PIII(D385) 24 0 0.0 0 0.0 24 100 0 0.0 26 0 0.0 0 0.0 26 100 0 0.0 111 1 0.9 0 0.0 110 99.1 0 0.0

Creatinine

PRE 31 0 0.0 2 6.5 29 93.5 0 0.0 30 0 0.0 2 6.7 27 90.0 1 3.3 118 1 0.8 14 11.9 101 85.6 2 1.7

PI(D7) 30 0 0.0 0 0.0 29 96.7 1 3.3 30 0 0.0 4 13.3 24 80.0 2 6.7 118 0 0.0 13 11.0 104 88.1 1 0.8 PI(D21) 30 0 0.0 2 6.7 28 93.3 0 0.0 29 0 0.0 4 13.8 24 82.8 1 3.4 115 0 0.0 15 13.0 100 87.0 0 0.0

PII(D28) 30 0 0.0 2 6.7 28 93.3 0 0.0 28 0 0.0 4 14.3 23 82.1 1 3.6 116 0 0.0 13 11.2 101 87.1 2 1.7

PII(D42) 30 0 0.0 0 0.0 30 100 0 0.0 28 1 3.6 4 14.3 22 78.6 1 3.6 116 0 0.0 12 10.3 104 89.7 0 0.0 PII(D182) 27 1 3.7 4 14.8 22 81.5 0 0.0 27 0 0.0 5 18.5 21 77.8 1 3.7 115 1 0.9 11 9.6 102 88.7 1 0.9

PIII(D191) 27 0 0.0 3 11.1 23 85.2 1 3.7 27 0 0.0 6 22.2 20 74.1 1 3.7 115 0 0.0 12 10.4 103 89.6 0 0.0

PIII(D385) 24 0 0.0 1 4.2 23 95.8 0 0.0 26 0 0.0 4 15.4 20 76.9 2 7.7 111 1 0.9 12 10.8 97 87.4 1 0.9

Eosinophils

PRE 31 0 0.0 6 19.4 24 77.4 1 3.2 30 0 0.0 3 10.0 27 90.0 0 0.0 118 0 0.0 30 25.4 87 73.7 1 0.8 PI(D7) 30 2 6.7 8 26.7 19 63.3 1 3.3 30 0 0.0 2 6.7 28 93.3 0 0.0 118 2 1.7 21 17.8 94 79.7 1 0.8

PI(D21) 30 1 3.3 7 23.3 22 73.3 0 0.0 29 0 0.0 5 17.2 24 82.8 0 0.0 115 5 4.3 25 21.7 82 71.3 3 2.6

PII(D28) 30 0 0.0 7 23.3 22 73.3 1 3.3 28 0 0.0 3 10.7 25 89.3 0 0.0 116 0 0.0 20 17.2 93 80.2 3 2.6 PII(D42) 30 0 0.0 3 10.0 26 86.7 1 3.3 28 0 0.0 3 10.7 25 89.3 0 0.0 116 0 0.0 24 20.7 90 77.6 2 1.7

PII(D182) 27 0 0.0 5 18.5 21 77.8 1 3.7 27 0 0.0 2 7.4 25 92.6 0 0.0 115 1 0.9 12 10.4 97 84.3 5 4.3

PIII(D191) 27 0 0.0 5 18.5 22 81.5 0 0.0 27 0 0.0 2 7.4 25 92.6 0 0.0 115 0 0.0 10 8.7 102 88.7 3 2.6 PIII(D385) 24 0 0.0 7 29.2 16 66.7 1 4.2 26 0 0.0 1 3.8 25 96.2 0 0.0 111 1 0.9 25 22.5 82 73.9 3 2.7

Hematocrit

PRE 31 0 0.0 5 16.1 26 83.9 0 0.0 30 0 0.0 4 13.3 25 83.3 1 3.3 118 0 0.0 4 3.4 108 91.5 6 5.1

PI(D7) 30 2 6.7 4 13.3 24 80.0 0 0.0 30 0 0.0 3 10.0 26 86.7 1 3.3 118 2 1.7 6 5.1 106 89.8 4 3.4

PI(D21) 30 1 3.3 3 10.0 26 86.7 0 0.0 29 0 0.0 5 17.2 23 79.3 1 3.4 115 5 4.3 9 7.8 99 86.1 2 1.7 PII(D28) 30 0 0.0 5 16.7 25 83.3 0 0.0 28 0 0.0 7 25.0 20 71.4 1 3.6 116 0 0.0 8 6.9 105 90.5 3 2.6

PII(D42) 30 0 0.0 5 16.7 25 83.3 0 0.0 28 0 0.0 7 25.0 20 71.4 1 3.6 116 0 0.0 11 9.5 102 87.9 3 2.6

PII(D182) 27 0 0.0 4 14.8 23 85.2 0 0.0 27 0 0.0 2 7.4 23 85.2 2 7.4 115 1 0.9 11 9.6 102 88.7 1 0.9 PIII(D191) 27 0 0.0 3 11.1 24 88.9 0 0.0 27 0 0.0 1 3.7 25 92.6 1 3.7 115 0 0.0 7 6.1 106 92.2 2 1.7

PIII(D385) 24 0 0.0 2 8.3 22 91.7 0 0.0 26 0 0.0 1 3.8 24 92.3 1 3.8 111 1 0.9 7 6.3 99 89.2 4 3.6

Hemoglobin

PRE 31 0 0.0 5 16.1 26 83.9 0 0.0 30 0 0.0 8 26.7 21 70.0 1 3.3 118 0 0.0 9 7.6 106 89.8 3 2.5

PI(D7) 30 2 6.7 3 10.0 25 83.3 0 0.0 30 0 0.0 9 30.0 20 66.7 1 3.3 118 2 1.7 14 11.9 101 85.6 1 0.8 PI(D21) 30 1 3.3 4 13.3 25 83.3 0 0.0 29 0 0.0 7 24.1 21 72.4 1 3.4 115 5 4.3 16 13.9 92 80.0 2 1.7

PII(D28) 30 0 0.0 6 20.0 24 80.0 0 0.0 28 0 0.0 10

35.7 17 60.7 1 3.6 116 0 0.0 13 11.2 101 87.1 2 1.7

PII(D42) 30 0 0.0 8 26.7 22 73.3 0 0.0 28 0 0.0 10

35.7 17 60.7 1 3.6 116 0 0.0 13 11.2 102 87.9 1 0.9

PII(D182) 27 0 0.0 5 18.5 22 81.5 0 0.0 27 0 0.0 9 33.3 18 66.7 0 0.0 115 1 0.9 17 14.8 96 83.5 1 0.9

PIII(D191) 27 0 0.0 6 22.2 21 77.8 0 0.0 27 0 0.0 6 22.2 21 77.8 0 0.0 115 0 0.0 14 12.2 100 87.0 1 0.9

PIII(D385) 24 0 0.0 6 25.0 18 75.0 0 0.0 26 0 0.0 9 34.6 16 61.5 1 3.8 111 1 0.9 15 13.5 95 85.6 0 0.0 Lymphocytes

PRE 31 0 0.0 0 0.0 30 96.8 1 3.2 30 0 0.0 0 0.0 30 100 0 0.0 118 0 0.0 0 0.0 117 99.2 1 0.8

PI(D7) 30 2 6.7 0 0.0 27 90.0 1 3.3 30 0 0.0 0 0.0 30 100 0 0.0 118 2 1.7 2 1.7 114 96.6 0 0.0

PI(D21) 30 1 3.3 0 0.0 28 93.3 1 3.3 29 0 0.0 0 0.0 29 100 0 0.0 115 5 4.3 0 0.0 110 95.7 0 0.0

PII(D28) 30 0 0.0 0 0.0 29 96.7 1 3.3 28 0 0.0 0 0.0 28 100 0 0.0 116 0 0.0 0 0.0 116 100 0 0.0 PII(D42) 30 0 0.0 0 0.0 29 96.7 1 3.3 28 0 0.0 1 3.6 27 96.4 0 0.0 116 0 0.0 1 0.9 114 98.3 1 0.9

PII(D182) 27 0 0.0 0 0.0 26 96.3 1 3.7 27 0 0.0 0 0.0 27 100 0 0.0 115 1 0.9 0 0.0 114 99.1 0 0.0

PIII(D191) 27 0 0.0 0 0.0 26 96.3 1 3.7 27 0 0.0 0 0.0 27 100 0 0.0 115 0 0.0 1 0.9 114 99.1 0 0.0 PIII(D385) 24 0 0.0 0 0.0 23 95.8 1 4.2 26 0 0.0 0 0.0 26 100 0 0.0 111 1 0.9 0 0.0 109 98.2 1 0.9

Monocytes

PRE 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 3 10.0 27 90.0 0 0.0 118 0 0.0 8 6.8 110 93.2 0 0.0

PI(D7) 30 2 6.7 0 0.0 28 93.3 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 118 2 1.7 14 11.9 102 86.4 0 0.0 PI(D21) 30 1 3.3 3 10.0 26 86.7 0 0.0 29 0 0.0 2 6.9 27 93.1 0 0.0 115 5 4.3 18 15.7 92 80.0 0 0.0

PII(D28) 30 0 0.0 1 3.3 29 96.7 0 0.0 28 0 0.0 2 7.1 26 92.9 0 0.0 116 0 0.0 13 11.2 103 88.8 0 0.0

PII(D42) 30 0 0.0 2 6.7 28 93.3 0 0.0 28 0 0.0 3 10.7 25 89.3 0 0.0 116 0 0.0 17 14.7 99 85.3 0 0.0

PII(D182) 27 0 0.0 2 7.4 25 92.6 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0 115 1 0.9 12 10.4 102 88.7 0 0.0 PIII(D191) 27 0 0.0 1 3.7 26 96.3 0 0.0 27 0 0.0 2 7.4 25 92.6 0 0.0 115 0 0.0 12 10.4 103 89.6 0 0.0

PIII(D385) 24 0 0.0 4 16.7 20 83.3 0 0.0 26 0 0.0 0 0.0 26 100 0 0.0 111 1 0.9 14 12.6 96 86.5 0 0.0

Neutrophils

PRE 31 0 0.0 1 3.2 29 93.5 1 3.2 30 0 0.0 1 3.3 28 93.3 1 3.3 118 0 0.0 2 1.7 113 95.8 3 2.5 PI(D7) 30 2 6.7 0 0.0 27 90.0 1 3.3 30 0 0.0 0 0.0 30 100 0 0.0 118 2 1.7 1 0.8 114 96.6 1 0.8

PI(D21) 30 1 3.3 0 0.0 28 93.3 1 3.3 29 0 0.0 1 3.4 27 93.1 1 3.4 115 5 4.3 3 2.6 102 88.7 5 4.3

PII(D28) 30 0 0.0 1 3.3 28 93.3 1 3.3 28 0 0.0 1 3.6 27 96.4 0 0.0 116 0 0.0 4 3.4 109 94.0 3 2.6

PII(D42) 30 0 0.0 1 3.3 28 93.3 1 3.3 28 0 0.0 1 3.6 27 96.4 0 0.0 116 0 0.0 3 2.6 112 96.6 1 0.9 PII(D182) 27 0 0.0 0 0.0 26 96.3 1 3.7 27 0 0.0 0 0.0 26 96.3 1 3.7 115 1 0.9 0 0.0 111 96.5 3 2.6

PIII(D191) 27 0 0.0 0 0.0 26 96.3 1 3.7 27 0 0.0 1 3.7 25 92.6 1 3.7 115 0 0.0 3 2.6 110 95.7 2 1.7

PIII(D385) 24 0 0.0 0 0.0 23 95.8 1 4.2 26 0 0.0 0 0.0 26 100 0 0.0 111 1 0.9 1 0.9 105 94.6 4 3.6 Platelets

PRE 31 1 3.2 1 3.2 29 93.5 0 0.0 30 1 3.3 1 3.3 28 93.3 0 0.0 118 2 1.7 1 0.8 112 94.9 3 2.5

PI(D7) 30 2 6.7 1 3.3 26 86.7 1 3.3 30 1 3.3 0 0.0 29 96.7 0 0.0 118 4 3.4 1 0.8 111 94.1 2 1.7

PI(D21) 30 1 3.3 1 3.3 28 93.3 0 0.0 29 0 0.0 1 3.4 28 96.6 0 0.0 115 6 5.2 1 0.9 107 93.0 1 0.9 PII(D28) 30 0 0.0 1 3.3 29 96.7 0 0.0 28 0 0.0 1 3.6 27 96.4 0 0.0 116 0 0.0 1 0.9 114 98.3 1 0.9

PII(D42) 30 0 0.0 1 3.3 29 96.7 0 0.0 28 0 0.0 1 3.6 27 96.4 0 0.0 116 0 0.0 1 0.9 114 98.3 1 0.9

PII(D182) 27 0 0.0 1 3.7 26 96.3 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0 115 1 0.9 0 0.0 113 98.3 1 0.9

PIII(D191) 27 0 0.0 1 3.7 26 96.3 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0 115 0 0.0 1 0.9 113 98.3 1 0.9 PIII(D385) 24 0 0.0 1 4.2 23 95.8 0 0.0 26 1 3.8 0 0.0 25 96.2 0 0.0 111 1 0.9 2 1.8 107 96.4 1 0.9

Erythrocytes (Red Blood Cells)

PRE 31 0 0.0 2 6.5 29 93.5 0 0.0 30 0 0.0 5 16.7 25 83.3 0 0.0 118 0 0.0 8 6.8 107 90.7 3 2.5

PI(D7) 30 2 6.7 3 10.0 25 83.3 0 0.0 30 0 0.0 5 16.7 25 83.3 0 0.0 118 2 1.7 12 10.2 103 87.3 1 0.8 PI(D21) 30 1 3.3 4 13.3 25 83.3 0 0.0 29 0 0.0 4 13.8 25 86.2 0 0.0 115 5 4.3 14 12.2 94 81.7 2 1.7

PII(D28) 30 0 0.0 2 6.7 28 93.3 0 0.0 28 0 0.0 5 17.9 23 82.1 0 0.0 116 0 0.0 15 12.9 101 87.1 0 0.0

PII(D42) 30 0 0.0 3 10.0 27 90.0 0 0.0 28 0 0.0 8 28.6 20 71.4 0 0.0 116 0 0.0 13 11.2 103 88.8 0 0.0 PII(D182) 27 0 0.0 1 3.7 26 96.3 0 0.0 27 0 0.0 3 11.1 24 88.9 0 0.0 115 1 0.9 10 8.7 103 89.6 1 0.9

PIII(D191) 27 0 0.0 1 3.7 26 96.3 0 0.0 27 0 0.0 2 7.4 25 92.6 0 0.0 115 0 0.0 9 7.8 106 92.2 0 0.0

PIII(D385) 24 0 0.0 2 8.3 22 91.7 0 0.0 26 0 0.0 4 15.4 22 84.6 0 0.0 111 1 0.9 5 4.5 104 93.7 1 0.9

Urea Nitrogen

PRE 31 0 0.0 0 0.0 31 100 0 0.0 30 0 0.0 0 0.0 29 96.7 1 3.3 118 1 0.8 0 0.0 115 97.5 2 1.7 PI(D7) 30 0 0.0 0 0.0 30 100 0 0.0 30 0 0.0 0 0.0 30 100 0 0.0 118 0 0.0 3 2.5 114 96.6 1 0.8

PI(D21) 30 0 0.0 0 0.0 29 96.7 1 3.3 29 0 0.0 1 3.4 28 96.6 0 0.0 115 0 0.0 2 1.7 110 95.7 3 2.6

PII(D28) 30 0 0.0 0 0.0 30 100 0 0.0 28 0 0.0 0 0.0 28 100 0 0.0 116 0 0.0 1 0.9 113 97.4 2 1.7 PII(D42) 30 0 0.0 0 0.0 30 100 0 0.0 28 1 3.6 0 0.0 26 92.9 1 3.6 116 0 0.0 1 0.9 115 99.1 0 0.0

PII(D182) 27 1 3.7 0 0.0 26 96.3 0 0.0 27 0 0.0 0 0.0 27 100 0 0.0 115 1 0.9 4 3.5 108 93.9 2 1.7

PIII(D191) 27 0 0.0 0 0.0 27 100 0 0.0 27 0 0.0 0 0.0 26 96.3 1 3.7 115 0 0.0 2 1.7 112 97.4 1 0.9

PIII(D385) 24 0 0.0 0 0.0 24 100 0 0.0 26 0 0.0 0 0.0 25 96.2 1 3.8 111 1 0.9 0 0.0 108 97.3 2 1.8 Leukocytes (White Blood Cells)

PRE 31 0 0.0 1 3.2 28 90.3 2 6.5 30 0 0.0 0 0.0 30 100 0 0.0 118 0 0.0 2 1.7 113 95.8 3 2.5

PI(D7) 30 2 6.7 0 0.0 27 90.0 1 3.3 30 0 0.0 0 0.0 30 100 0 0.0 118 2 1.7 2 1.7 112 94.9 2 1.7

PI(D21) 30 1 3.3 1 3.3 27 90.0 1 3.3 29 0 0.0 1 3.4 27 93.1 1 3.4 115 5 4.3 3 2.6 105 91.3 2 1.7 PII(D28) 30 0 0.0 1 3.3 28 93.3 1 3.3 28 0 0.0 0 0.0 28 100 0 0.0 116 0 0.0 5 4.3 109 94.0 2 1.7

PII(D42) 30 0 0.0 1 3.3 27 90.0 2 6.7 28 0 0.0 1 3.6 27 96.4 0 0.0 116 0 0.0 4 3.4 112 96.6 0 0.0

PII(D182) 27 0 0.0 0 0.0 26 96.3 1 3.7 27 0 0.0 0 0.0 26 96.3 1 3.7 115 1 0.9 1 0.9 110 95.7 3 2.6

PIII(D191) 27 0 0.0 1 3.7 25 92.6 1 3.7 27 0 0.0 1 3.7 25 92.6 1 3.7 115 0 0.0 2 1.7 111 96.5 2 1.7

PIII(D385) 24 0 0.0 0 0.0 22 91.7 2 8.3 26 0 0.0 0 0.0 26 100 0 0.0 111 1 0.9 2 1.8 104 93.7 4 3.6

N = number of subjects with laboratory results for the specified time point and laboratory parameter n/% = number/percentage of subjects in a given category Unknown = value unknown for the specified time point and laboratory parameter Below = value below the laboratory reference range defined for the specified time point and laboratory parameter Within = value within the laboratory reference range defined for the specified time point and laboratory parameter Above = value above the laboratory reference range defined for the specified time point and laboratory parameter ALAT = Alanine Aminotransferase AP = Alkaline Phosphatase ASAT = Aspartate Aminotransferase BUN = Blood Urea Nitrogen Pre = Pre-vaccination 1 at Day 0 PI(D7) = Post-vaccination 1 at Day 7 PI(D21) = Pre-vaccination 2 at Day 21 PII(D28) = Post-vaccination 2 at Day 28 PII(D42) = Post-vaccination 2 at Day 42 PII(D182) = Post-vaccination 2 at Day 182 PIII(D191) = Post-vaccination 3 at Day 191

PIII(D385) = Post-vaccination 3 at Day 385 Safety Results: Number (%) of subjects with unsolicited AEs occurring within a 21-day (Days 0-20) post-vaccination period following the first vaccination (Total Vaccinated cohort)

Most frequent adverse events - On-Therapy (occurring within Days 0-20 following vaccination)

Q-PAN-1A Group N = 61

Q-PAN-1B Group N = 60

Q-PAN-1C Group N = 60

Q-PAN-1D Group N = 61

Q-PAN-2 Group N = 60

Placebo Group N=118

Subjects with any AE(s), n (%) 14 (23.0) 17 (28.3) 16 (26.7) 17 (27.9) 15 (25.0) 34 (28.8)

Subjects with Related AE(s), n (%) 6 (9.8) 5 (8.3) 5 (8.3) 6 (9.8) 4 (6.7) 7 (5.9) Anaemia 1 (1.6) - - 1 (1.6) - -

Ear pain - - - - - -

Hypothyroidism - - 1 (1.7) - - - Abdominal pain 1 (1.6) - - - - - Abdominal pain upper - - - - - - Constipation - - - - - -

Diarrhoea - 1 (1.7) - - - - Dry mouth - - 1 (1.7) - - - Gastritis - - - - - -

Nausea - - - 1 (1.6) - -

Oral mucosal blistering - 1 (1.7) - - - - Toothache 1 (1.6) - - - - 3 (2.5)

Asthenia - - - - 1 (1.7) - Axillary pain 1 (1.6) - - - - - Injection site anaesthesia - 1 (1.7) - - - - Injection site haematoma - - 1 (1.7) - - - Injection site pain 1 (1.6) - - - - - Injection site pruritus - 2 (3.3) - - - - Malaise - - 1 (1.7) - - - Oedema peripheral - 1 (1.7) - - - - Bronchitis 1 (1.6) - - - 1 (1.7) - Cellulitis - 1 (1.7) - - - - Lower respiratory tract infection 1 (1.6) - - 1 (1.6) 1 (1.7) -

Nasopharyngitis 1 (1.6) - 1 (1.7) - 2 (3.3) 5 (4.2)

Oral herpes - - - - - -

Pharyngitis 1 (1.6) 1 (1.7) - - - -

Sinusitis - 1 (1.7) - - - - Tinea versicolour - - - 1 (1.6) - -

Tonsillitis - - - - - -

Upper respiratory tract infection 1 (1.6) 4 (6.7) 1 (1.7) 3 (4.9) 3 (5.0) 3 (2.5)

Urinary tract infection - - - 1 (1.6) - -

Viral infection - - - - - -

Arthropod bite - 1 (1.7) - - - - Arthropod sting - 1 (1.7) - - - - Burns second degree - - 1 (1.7) - - - Contusion - - 1 (1.7) - - -

Eye injury - - 1 (1.7) - - - Joint injury - - - - - -

Laceration - - 1 (1.7) - - - Ligament sprain - - 1 (1.7) 1 (1.6) 1 (1.7) 3 (2.5)

Muscle strain - - - 1 (1.6) - -

Blood pressure increased - - 1 (1.7) - - - Haematocrit decreased - - - 1 (1.6) - -

Haemoglobin decreased - - - 1 (1.6) - - Transaminases increased - - - - -

Arthralgia 1 (1.6) 1 (1.7) - 1 (1.6) - -

Back pain - 1 (1.7) - 1 (1.6) - -

Costochondritis - 1 (1.7) - - - - Musculoskeletal chest pain - - - 1 (1.6) - -

Musculoskeletal pain - - - - - -

Musculoskeletal stiffness - 1 (1.7) - - - - Myalgia 1 (1.6) - - - 1 (1.7) - Neck pain - - - - 1 (1.7) - Pain in extremity - - - 1 (1.6) - -

Tendon disorder - - - - - - Carpal tunnel syndrome 1 (1.6) - - - - - Dizziness 1 (1.6) - - - - -

Headache 1 (1.6) 3 (5.0) - - 3 (5.0) - Hypoaesthesia - - 1 (1.7) 2 (3.3) - -

Paraesthesia - - - 1 (1.6) - -

Insomnia - - 1 (1.7) - - - Amenorrhoea - - - 1 (1.6) - -

Cough 2 (3.3) - - 1 (1.6) 1 (1.7) -

Dyspnoea - - - 1 (1.6) - -

Nasal congestion - - 1 (1.7) - - -

Oropharyngeal pain 2 (3.3) 3 (5.0) 1 (1.7) 3 (4.9) 1 (1.7) 3 (2.5) Rhinitis allergic - - - - 1 (1.7) - Rhinorrhoea 3 (4.9) - - 1 (1.6) - -

Sinus congestion - - - - - -

Throat irritation - 1 (1.7) - - 1 (1.7) - Dermatitis contact - - - - - -

Pruritus generalised - - - - 1 (1.7) - Rash - - - 1 (1.6) - -

Rash pruritic - - 1 (1.7) - - - Peripheral coldness - - - - - - Counting rule applied: As there were more than 30 subjects per treatment group and >3 groups, only the 5 most frequent events in each treatment group were listed. -: Implies that adverse event was not reported in the particular group or that the adverse event was reported in the particular group but did not fall within the pre-defined counting rule of 5 most frequent events for that group.

Safety Results: Number (%) of subjects with unsolicited AEs occurring within a 21-day (Days 21-42) post-vaccination period following the second vaccination (Total Vaccinated cohort)

Most frequent adverse events - On-Therapy (occurring within Days 21-42 following vaccination)

Q-PAN-1A Group N = 59

Q-PAN-1B Group N = 59

Q-PAN-1C Group N = 56

Q-PAN-1D Group N = 58

Q-PAN-2 Group N = 58

Placebo Group N = 112

Subjects with any AE(s), n (%) 10 (16.9) 17 (28.8) 12 (21.4) 10 (17.2) 21 (36.2) 27 (24.1)

Subjects with Related AE(s), n (%) 1 (1.7) 4 (6.8) 3 (5.4) 1 (1.7) 4 (6.9) 2 (1.8) Anaemia - - - - - -

Lymphadenitis - - - - 1 (1.7) -

Lymphadenopathy - - - - - - Conjunctival hyperaemia - - - - 1 (1.7) -

Lacrimation increased - - - - 1 (1.7) -

Diarrhoea - - - - 1 (1.7) - Dyspepsia - - - - 1 (1.7) -

Nausea - 2 (3.4) - - - -

Toothache - - 1 (1.8) - - - Vomiting - 2 (3.4) - - -

Injection site warmth - - 1 (1.8) - - -

Oedema peripheral - - - - -

Pain - - 1 (1.8) - - - Bronchitis - - 1 (1.8) - 1 (1.7) -

Cellulitis 1 (1.7) - - - - -

Gastroenteritis - - 1 (1.8) - - Nasopharyngitis 2 (3.4) 4 (6.8) 3 (5.4) - 3 (5.2) 6 (5.4)

Oral herpes - - - 1 (1.7) - -

Pharyngitis - - - - 1 (1.7) -

Pharyngitis streptococcal - - - 1 (1.7) - - Sinusitis - - 1 (1.8) - - -

Tooth abscess - - - - - -

Tooth infection - - - - 1 (1.7) Upper respiratory tract infection 3 (5.1) 3 (5.1) 2 (3.6) 2 (3.4) 6 (10.3) 3 (2.7)

Vulvovaginal candidiasis - - - - - -

Contusion - - - - - - Hand fracture 1 (1.7) - - - - -

Laceration 1 (1.7) - - - - -

Ligament sprain - - 1 (1.8) - -

Tooth fracture - - - - 1 (1.7) - Wound - - - - -

Alanine aminotransferase increased - - 1 (1.8) - 1 (1.7) 3 (2.7)

Aspartate aminotransferase increased - - - 1 (1.7) 1 (1.7) - Decreased appetite - - - - 1 (1.7) -

Hypoglycaemia - - - - - -

Vitamin b12 deficiency - - 1 (1.8) - - -

Arthralgia - - 1 (1.8) 1 (1.7) - - Back pain - - - - - -

Muscular weakness - - - - - -

Musculoskeletal stiffness - - - - - - Osteoarthritis - - - - 1 (1.7) -

Pain in extremity - - - - 2 (3.4) -

Dizziness 1 (1.7) 2 (3.4) - - - Headache - - - 1 (1.7) 1 (1.7) 3 (2.7)

Migraine 1 (1.7) - - - - -

Neuralgia - - - - - -

Sinus headache - - - 1 (1.7) - - Insomnia - - - - 1 (1.7) -

Haematuria 1 (1.7) - - - - -

Renal failure - - - - - - Cough 1 (1.7) - - - 1 (1.7) -

Nasal congestion - - 1 (1.8) - - -

Oropharyngeal pain 1 (1.7) - - - 2 (3.4) 4 (3.6) Rhinorrhoea - 2 (3.4) - 1 (1.7) - -

Sinus congestion - - - - 1 (1.7) -

Sneezing - - - 1 (1.7) - -

Throat irritation - - - - - - Upper respiratory tract congestion - - - - - -

Ecchymosis 1 (1.7) - - - - -

Erythema - - - - 1 (1.7) -

Hyperhidrosis - - - - 1 (1.7) - Rash papular - - - - 1 (1.7) -

Urticaria - - - - - -

Female sterilisation - - - - - - Deep vein thrombosis - - - - - -

Hot flush - - - - 1 (1.7) -

Hypertension - - - - - -

Thrombophlebitis superficial - - - 1 (1.7) - -

Counting rule applied: As there were more than 30 subjects per treatment group and >3 groups, only the 5 most frequent events in each treatment group were listed. -: Implies that adverse event was not reported in the particular group or that the adverse event was reported in the particular group but did not fall within the pre-defined counting rule of 5 most frequent events for that group.

Safety Results: Number (%) of subjects with unsolicited AEs occurring within a 21-day (Days 182-202) post-vaccination period following the third vaccination (Total Vaccinated cohort)

Most frequent adverse events - On-Therapy (occurring within Days 182-202 following vaccination)

Q-PAN-1A Group 1# N = 30

Q-PAN-1B Group 1# N = 28

Q-PAN-1C Group 1# N = 29

Q-PAN-1D Group 1# N = 27

Q-PAN-2 Group 1# N = 28

Subjects with any AE(s), n (%) 2 (6.7) 6 (21.4) 7 (24.1) 9 (33.3) 5 (17.9)

Subjects with Related AE(s), n (%) 0 (0.0) 0 (0.0) 1 (3.4) 0 (0.0) 1 (3.6)

Cardiac failure congestive - - - - - Ear discomfort - - - - -

Ear pain - - - - -

Abdominal distension - - - - -

Dyspepsia - - - - - Gastrooesophageal reflux disease - - - - -

Haemorrhoids - - - - -

Chest pain - - - - - Bronchitis - - - - -

Ear infection - - - - -

Nasopharyngitis - - - - -

Pharyngitis - - - - - Sinusitis - - - - -

Upper respiratory tract infection - 2 (7.1) - 3 (11.1) -

Joint injury - - - - - Ligament sprain - - - - -

Wrist fracture - - - - -

Arthralgia -- - - - - Back pain - - - - -

Myalgia - - - - -

Headache - - - - -

Depression - - - - - Nephrotic syndrome - - - - -

Asthma - - - - -

Cough - - - - - Nasal congestion - - - - -

Oropharyngeal pain - 2 (7.1) - - -

Pulmonary embolism - - - - - Rhinorrhoea - - - - -

Sneezing - - - - -

Hypertension - - - - -s

Most frequent adverse events - On-Therapy Q-PAN-1A Q-PAN-1B Q-PAN-1C Q-PAN-1D Q-PAN-2 Placebo

(occurring within Days 182-202 following vaccination)

Group 2# N = 24

Group 2# N = 29

Group 2# N = 26

Group 2# N = 26

Group 2# N = 25

Group$ N = 113

Subjects with any AE(s), n (%) 8 (33.3) 8 (27.6) 4 (15.4) 7 (26.9) 5 (20.0) 31 (27.4)

Subjects with Related AE(s), n (%) 2 (8.3) 1 (3.4) 1 (3.8) 0 (0.0) 1 (4.0) 0 (0.0)

Tinnitus - - - - - 1 (0.9)- Lip oedema - - - - - 1 (0.9)-

Proctalgia - - - - - 1 (0.9)-

Toothache - - - - - 1 (0.9)-

Influenza like illness - - - - - 1 (0.9)- Bronchitis - - - - - 1 (0.9)-

Cystitis - - - - - 1 (0.9)-

Nasopharyngitis 3 (12.5) - - - - 7 (6.2) Sinusitis - - - - - 1 (0.9)-

Subcutaneous abscess - - - - - 1 (0.9)-

Tooth abscess - - - - - 1 (0.9)- Upper respiratory tract infection - - - - - 4 (3.5)

Face injury - - - - - 1 (0.9)-

Ligament sprain - - - - - 3 (2.7)

Lip injury - - - - - 1 (0.9)- Procedural pain - - - - - 1 (0.9)

Tooth fracture - - - - - 1 (0.9)

Musculoskeletal chest pain - - - - - 1 (0.9) Headache - - - - - 2 (1.8)

Post herpetic neuralgia - - - - - 1 (0.9)

Libido decreased - - - - - 1 (0.9)

Cough - - - - - 1 (0.9) Nasal congestion - - - - 3 (12.0) 1 (0.9)

Oropharyngeal pain - - - - - 2 (1.8)

Rhinorrhoea - - - - - 1 (0.9) Hypertension - - - - - 1 (0.9)

-: Implies that adverse event was not reported in the particular group or that the adverse event was reported in the particular group but did not fall within the pre-defined counting rule of 10 most frequent events for that group. Detail of rule in studies with mixed groups: # As there were ≤30 subjects per treatment group, any AE that occurred in more than 1 subject in any group were listed $ As there were >30 subjects per treatment group and >3 groups, only the 5 most frequent events in each treatment group were listed. Safety Results: Number (%) of subjects with SAEs reported during the entire study period (Day 0 to Day 546) (Total Vaccinated cohort).

Serious Adverse Events – On-Therapy, n (%) [n considered by the investigator to be related to study medication]

All SAEs Q-PAN-1A Group 1 N = 31

Q-PAN-1B Group 1 N = 30

Q-PAN-1C Group 1 N = 30

Q-PAN-1D Group 1 N = 30

Q-PAN-2 Group 1

N = 30

Subjects with any SAE(s), n (%) [n assessed by the investigator as related]

0 (0.0) [0] 1 (3.3) [0] 4 (13.3) [0] 1 (3.3) [0] 4 (13.3) [0]

Abdominal pain 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0]

Asthma 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0]

Atrial fibrillation 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] Cardiac failure congestive 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0]

Cellulitis 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Depression 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] Foetal death 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0]

Hypertension 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0]

Intervertebral disc protrusion 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0]

Migraine 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] Nephrotic syndrome 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0]

Pneumonia 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0]

Pneumonia influenzal 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] Prinzmetal angina 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0]

Pulmonary embolism 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0]

Pyelonephritis 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] Sepsis 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0]

Staphylococcal infection 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0]

Thrombophlebitis superficial 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0]

Fatal SAEs Q-PAN-1A Group 1 N = 31

Q-PAN-1B Group 1 N = 30

Q-PAN-1C Group 1 N = 30

Q-PAN-1D Group 1 N = 30

Q-PAN-2 Group 1

N = 30 Subjects with fatal SAE(s), n (%) [n assessed by the investigator as related]

0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

All SAEs Q-PAN-1A

Group 2 N = 30

Q-PAN-1B Group 2 N = 30

Q-PAN-1C Group 2 N = 30

Q-PAN-1D Group 2 N = 31

Q-PAN-2 Group 2 N = 30

Placebo Group

N = 118

Subjects with any SAE(s), n (%) [n assessed by the investigator as related]

2 (6.7) [0] 1 (3.3) [0] 2 (6.7) [0] 1 (3.2) [0] 0 (0.0) [0] 2 (1.7) [0]

Deep vein thrombosis 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.8) [0]

Atrial fibrillation 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Benign intracranial hypertension 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Cellulitis 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Cholecystitis acute 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Chronic obstructive pulmonary disease 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Iron deficiency anaemia 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.8) [0] Osteoarthritis 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (3.2) [0] 0 (0.0) [0] 0 (0.0) [0]

Pulmonary embolism 0 (0.0) [0] 0 (0.0) [0] 1 (3.3) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Schizophreniform disorder 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.8) [0]

Fatal SAEs Q-PAN-1A Group 2 N = 30

Q-PAN-1B Group 2 N = 30

Q-PAN-1C Group 2 N = 30

Q-PAN-1D Group 2 N = 31

Q-PAN-2 Group 2 N = 30

Placebo Group

N = 118 Subjects with fatal SAE(s), n (%) [n assessed by the investigator as related]

0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0]

Conclusion: At Day 21, the SCR for HI antibodies against Flu A/chicken/Hong Kong/G9/97 (H9N2) was 96.8% in Q-PAN-1A Group 1, 96.4% in Q-PAN-1A Group 2, 82.8% in Q-PAN-1B Group 1, 96.7% in Q-PAN-1B Group 2, 96.4% in Q-PAN-1C Group 1, 92.9% in Q-PAN-1C Group 2, 93.1% in Q-PAN-1D Group 1 and 93.3% in Q-PAN-1D Group 2. At Day 42, the SCR for HI antibodies against Flu A/chicken/Hong Kong/G9/97 (H9N2) was 100% in Q-PAN-1A Group 1, 95.8% in Q-PAN-1A Group 2, 96.2% in Q-PAN-1B Group 1, 100% in Q-PAN-1B Group 2, 100% in Q-PAN-1C Group 1, 96.2% in Q-PAN-1C Group 2, 100% in Q-PAN-1D Group 1 and 96.6% in Q-PAN-1D Group 2.

At Day 21, the SPR for HI antibodies against Flu A/chicken/Hong Kong/G9/97 (H9N2) was 100% each in Q-PAN-1A Groups 1 and 2, 93.1% in Q-PAN-1B Group 1, 96.7% in Q-PAN-1B Group 2, 100% each in Q-PAN-1C Groups 1 and 2, 96.6% in Q-PAN-1D Group 1 and 100% in Q-PAN-1D Group 2. At Day 42, the SCR for HI antibodies against Flu A/chicken/Hong Kong/G9/97 (H9N2) was 100% in Q-PAN-1A group, Q-PAN-1B group, Q-PAN-1C group and Q-PAN-1D group, respectively

At Day 21, the MGI for HI antibodies against Flu A/chicken/Hong Kong/G9/97 (H9N2) was 42.5 in Q-PAN-1A Group 1, 33.2 in Q-PAN-1A Group 2, 14.7 in Q-PAN-1B Group 1, 32.8 in Q-PAN-1B Group 2, 52.1 in Q-PAN-1C Group 1, 37.0 in Q-PAN-1C Group 2, 31.2 in Q-PAN-1D Group 1 and 26.2 in Q-PAN-1D Group 2. At Day 42, the MGI for HI antibodies against Flu A/chicken/Hong Kong/G9/97 (H9N2) was 107.9 in Q-PAN-1A Group 1, 130.2 in Q-PAN-1A Group 2, 68.2 in Q-PAN-1B Group 1, 109.4 in Q-PAN-1B Group 2, 136.2 in Q-PAN-1C Group 1, 112.4 in Q-PAN-1C Group 2, 96.5 in Q-PAN-1D Group 1 and 83.7 in Q-PAN-1D Group 2.

During the 21-day post-vaccination period following the first vaccination (Days 0-21), at least one unsolicited AE was reported for 14 (23.0%) subjects in Q-PAN-1A group, for 17 (28.3%) subjects in Q-PAN-1B group, for 16 (26.7%) subjects in Q-PAN-1C group, for 17 (27.9%) subjects in Q-PAN-1D group, for 15 (25.0%) subjects in Q-PAN-2 group and 34 (28.8%) subjects in Placebo group. During the same period, at least one unsolicited AE assessed by the investigator as casually related to study vaccination was reported for 6 (9.8%) subjects in Q-PAN-1A group, for 5 (8.3%) subjects in Q-PAN-1B group, for 5 (8.3%) subjects in Q-PAN-1C group, for 6 (9.8%) subjects in Q-PAN-1D group, for 4 (6.7%) subjects in Q-PAN-2 group and for 7 (5.9%) subjects in Placebo group.

During the 21-day post-vaccination period following the second vaccination (Days 21-41), at least one unsolicited AE was reported for 10 (16.9%) subjects in Q-PAN-1A group, for 17 (28.8%) subjects in Q-PAN-1B group, for 12 (21.4%) subjects in Q-PAN-1C group, for 10 (17.2%) subjects in Q-PAN-1D group, for 21 (36.2%) subjects in Q-PAN-2 group and 27 (24.1%) subjects in Placebo group. During the same period, at least one unsolicited AE assessed by the investigator as casually related to study vaccination was reported for 1 (1.7%) subjects in Q-PAN-1A group, for 4 (6.8%) subjects in Q-PAN-1B group, for 3 (5.4%) subjects in Q-PAN-1C group, for 1 (1.7%) subjects in Q-PAN-1D group, for 4 (6.9%) subjects in Q-PAN-2 group and for 2 (1.8%) subjects in Placebo group.

During the 21-day post-vaccination period following the third vaccination (Days 182-202), at least one unsolicited AE was reported for 2 (6.7%) subjects in Q-PAN-1A Group 1, 6 (21.4%) subjects in Q-PAN-1B Group 1, 7 (24.1%) subjects in Q-PAN-1C Group 1, 9 (33.3%) subjects in Q-PAN-1D Group 1, 5 (17.9%) subjects in Q-PAN-2 Group 1, 8 (33.3%) subjects in Q-PAN-1A Group 2, 8 (27.6%) subjects in Q-PAN-1B Group 2, 4 (15.4%) subjects in Q-PAN-1C Group 2, 7 (26.9%) subjects in Q-PAN-1D Group 2, 5 (20.0%) subjects in Q-PAN-2 Group 2 and 31 (27.4%) subjects in Placebo Group. During the same period, at least one unsolicited AE assessed by the investigator as casually related to study vaccination was reported for 1 (3.6%) subjects in Q-PAN-2 Group 1, 2 (8.3%) subjects in Q-PAN-1A Group 2, 1 (3.4%) subject in Q-PAN-1B Group 2, 1 (3.8%) subject in Q-PAN-1C Group 2 and 1 (4.0%) subject in Q-PAN-2 Group 2 and none were reported in Q-PAN-1A Group 1, Q-PAN-1B Group 1, Q-PAN-1D Group 1, Q-PAN-1D Group 2 and Placebo Group, respectively.

During the entire study period (Day 0 to 546), SAEs were reported for 1 (3.3%) subject in Q-PAN-1B Group 1, 4 (13.3%) subjects in Q-PAN-1C Group 1, 1 (3.3%) subject in Q-PAN-1D Group 1, 4 (13.3%) subjects in Q-PAN-2 Group 1, 2 (6.7%) subjects in Q-PAN-1A Group 2, 1 (3.3%) subjects in Q-PAN-1B Group 2, 2 (6.7%) subjects in Q-PAN-1C Group 2, 1 (3.2%) subject in Q-PAN-1D Group 2 and 2 (1.7%) subjects in Placebo Group. None of the SAEs were assessed by the investigators as related to the study vaccination. No SAEs were reported in Q-PAN-1A Group 1 and Q-PAN-2 Group 2. No fatal SAEs were reported during the entire study period.

Date updated: 15 September 2016