STATISTICAL ANALYSIS PLAN Protocol No.: BT-201 · Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0 Novotech - Strictly Confidential Page

Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0

Novotech - Strictly Confidential Page 1 of 44

STATISTICAL ANALYSIS PLAN

A Phase 1b/2a, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Plasma gelsolin (rhu-pGSN) Added to Standard of Care in Subjects Hospitalized for Acute

Community-acquired Pneumonia (CAP)

Protocol No.: BT-201

Product Code: rhu-pGSN

PREPARED FOR: BioAegis Therapeutics, Inc. (BTI) 675 US-1, North Brunswick Township, NJ 08902, USA Phone: +1 203-952-6373

PREPARED BY: Novotech (Australia) Pty Ltd Level 3, 235 Pyrmont Street Pyrmont, NSW, 2009 Australia

DATE OF ISSUE: 27 August 2018 (Draft Version 0.1) 19 September 2018 (Draft Version 0.5) 03 October 2018 (Final Draft 0.9) 02 November 2018 (Final 1.0) 03 December 2018 (Final 2.0 Amendment 1.0)

VERSION/STATUS: Final 2.0 Amendment 1.0

VERSION DATE: 03 December 2018

AUTHOR: Jan Steyn



SUMMARY OF CHANGES FROM SAP VERSION 1.0

Section 11.2.2 page 25, the following text has been added:

Additionally, counts (%) of number subjects with values out of normal range at each scheduled time point will also be presented along with shift tables that will represent the changes in normal range categories across post-baseline time points.

Section 17, the following tables have been added:

No. Title Analysis

Population

14.3.4.1.2.1 SD: Summary of CBC Shifts from Baseline (Low, Normal, High) Safety 14.3.4.1.2.2 MAD: Summary of CBC Shifts from Baseline (Low, Normal, High) Safety 14.3.4.2.2.1 SD: Summary of Coagulation Shifts from Baseline

(Low, Normal, High) Safety

14.3.4.2.2.2 MAD: Summary of Coagulation Shifts from Baseline (Low, Normal, High) Safety

14.3.4.3.2.1 SD: Summary of Comprehesive Metabolic Profile Shifts from Baseline (Low, Normal, High)

Safety

14.3.4.3.2.2 MAD: Summary of Comprehesive Metabolic Profile Shifts from Baseline (Low, Normal, High) Safety

Section 18, the following listings have been added:

No. Title Analysis Population

16.2.8.1.2.1 SD: Abnormal CBC Intent-to-Treat 16.2.8.1.2.2 MAD: Abnormal CBC Intent-to-Treat 16.2.8.2.2.1 SD: Abnormal Coagulation Intent-to-Treat 16.2.8.2.2.2 MAD: Abnormal Coagulation Intent-to-Treat 16.2.8.3.2.1 SD: Abnormal Comprehensive Metabolic Profile Intent-to-Treat 16.2.8.3.2.2 MAD: Abnormal Comprehensive Metabolic Profile Intent-to-Treat



Table of contents

1. INTRODUCTION .................................................................................................................... 8

2. PROJECT OVERVIEW ............................................................................................................ 9

2.1 Study Design ............................................................................................................................. 9

2.2 Objectives ................................................................................................................................. 9

2.3 Sample Size ............................................................................................................................. 10

2.4 Randomization ........................................................................................................................ 10

3. STATISTICAL CONSIDERATIONS ......................................................................................... 11

4. ANALYSIS POPULATIONS .................................................................................................... 13

4.1 Population Descriptions ......................................................................................................... 13

5. PROTOCOL DEVIATIONS..................................................................................................... 14

6. SUBJECT DISPOSITION ........................................................................................................ 15

7. DEMOGRAPHIC AND BASELINE INFORMATION ................................................................ 16

7.1 Demographics ......................................................................................................................... 16

7.2 Medical history ....................................................................................................................... 16

7.3 Pregnancy Test (Serum and Urine) ......................................................................................... 16

7.4 Serology .................................................................................................................................. 16

7.5 Other baseline characteristics ................................................................................................ 16

8. STUDY DRUG ADMINISTRATION ........................................................................................ 17

9. PHARMACOKINETICS (PK) .................................................................................................. 18

9.1 Definition of variables ............................................................................................................ 18

9.2 Biostatistical methods ............................................................................................................ 19

10. PHARMACODYNAMICS (Efficacy) ................................................................................... 22

10.1 Definition of variables ............................................................................................................ 22

10.2 Biostatistical methods ............................................................................................................ 22

11. SAFETY ............................................................................................................................ 23

11.1 Adverse Events ....................................................................................................................... 23

11.2 Safety Laboratory Assessments .............................................................................................. 24

11.3 Vital Signs Measurements ...................................................................................................... 26

11.4 12 - Lead Electrocardiogram (EKG) ......................................................................................... 27

11.5 Physical Examinations ............................................................................................................ 27

11.6 Outcome Prediction Models .................................................................................................. 27

11.7 Concomitant Medications ...................................................................................................... 28

11.8 Other safety evaluations ........................................................................................................ 28

12. IMMUNOGENICITY ENDPOINTS ..................................................................................... 30



13. EXPLORATORY ENDPOINTS ............................................................................................ 31

14. HANDLING OF MISSING DATA........................................................................................ 32

15. CHANGES TO THE PLANNED ANALYSIS .......................................................................... 33

15.1 Final Analysis (End of Study) ................................................................................................... 34

16. SOFTWARE ..................................................................................................................... 35

17. TABLES ............................................................................................................................ 36

18. LISTINGS ......................................................................................................................... 39

19. FIGURES .......................................................................................................................... 42

20. APPENDICES ................................................................................................................... 43

21. REFERENCES ................................................................................................................... 44



List of Abbreviations

Abbreviation Description

AUC0-t The area under the plasma concentration-time curve, from time 0 (time of dosing) to the last time point with measurable analyte concentration, calculated by the log down, linear up trapezoidal method.

AE Adverse Event ATC Anatomical Therapeutic Class

AUC0-inf The area under the plasma concentration-time curve from time 0 extrapolated to infinity. AUC0-inf is calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant (kel).

AUC0-8 The area under the plasma concentration-time curve, from time 0 (time of dosing) to the 8 hours concentration, calculated by the log down, linear up trapezoidal method.

BLQ Below the quantitation limit

CAP Community-Acquired Pneumonia CBC Complete Blood Count

Cmax Maximum observed concentration Cmin Minimum observed concentration over the dosing interval.

CL/F Apparent clearance calculated as Dose/AUC0-inf.

CS Clinically Significant CSR Clinical Study Report

CV Coefficient of variation DLT Dose Limiting Toxicity

DN_AUC0-inf Dose-normalized AUC0-inf, calculated as AUC0-inf divided by dose. DN_AUC0-t Dose-normalized AUC0-t, calculated as AUC0-t divided by dose.

DN_AUC0-8 Dose-normalized AUC0-8, calculated as AUC0-8 divided by dose.

DN_Cmax Dose-normalized Cmax, calculated as Cmax divided by dose.

EKG Electrocardiogram eCRF Electronic Case Report Form

EOS End of Study GCP Good Clinical Practice

geo CV Geometric Coefficient of Variation HIV Human Immunodeficiency Virus

ITT Intention-to-treat

IV Intravenous IWRS Interactive web response system

kel Apparent terminal elimination rate constant, calculated by linear regression of the terminal linear portion of the log concentration vs. time curve.

LLQ Lower Limit of Quantification MAD Multiple-Ascending Dose

MedDRA Medical Dictionary for Regulatory Activities MMSE Mini-Mental State Exam

N/A Not Applicable

NCS Not Clinically Significant



Abbreviation Description

NK Not Known

PE Physical Examination

PI Principal Investigator PK Pharmacokinetic

PP Per Protocol PSI Pneumonia Severity Index

PT Preferred Term rhu-pGSN Recombinant human plasma Gelsolin

SAE Serious Adverse Event

SAP Statistical Analysis Plan SD Single Dose

SD* Standard Deviation S.I. International System of Units

SOC* Standard of Care

SOC System Organ Class SOP Standard Operating Procedure

t½ Apparent elimination half-life, calculated as ln(2)/kel. TEAE Treatment Emergent Adverse Event

Tmax Time to maximum observed drug concentration. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value.

Vz/F Apparent volume of distribution at the terminal phase, calculated as Dose/ (kel × AUC0-inf).

WHO-DD World Health Organization Drug Dictionary



1. INTRODUCTION

The following Statistical Analysis Plan (SAP) provides the outline for the statistical analysis of the data from the BT-201 study. The planned analyses identified in this SAP may be included in clinical study reports (CSRs), regulatory submissions, or future manuscripts. Also, post hoc exploratory analyses not necessarily identified in this SAP may be performed to further examine study data. Any post hoc, or unplanned, exploratory analyses performed will be clearly identified as such in the final CSR.



2. PROJECT OVERVIEW

2.1 Study Design

Study BTI-201 is a Phase 1b/2a, double-blind, placebo-controlled, dose-escalation study to evaluate the safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of recombinant human plasma gelsolin (rhu-pGSN) added to standard of care (SOC*) in subjects hospitalized for acute community-acquired pneumonia (CAP). Each dosing cohort will include 8 subjects randomized 3:1 rhu-pGSN:placebo (6 rhu-pGSN subjects:2 placebo subjects).

There will be 1 single dose cohort (Cohort 1) and 3 multiple dose cohorts (Cohorts 2, 3 and 4).

Dose will be based on actual body weight. Dose escalation will involve 3 dose levels of rhu-pGSN (6, 12, and 24 mg/kg) in patients admitted for CAP. Dose escalation will only occur after post-therapy safety information on all subjects in the prior cohort has been reviewed at Day 7 for the single-dose (SD) and multiple-ascending dose (MAD*) arms.

The MAD portion of the study will commence once single doses of 6 mg/kg of rhu-pGSN are shown to be acceptably safe. The first 2 doses must be administered in the hospital, but the third dose can be given in a monitored outpatient setting where appropriate.

Discharged subjects will return for follow-up 7 days after the initiation of therapy (Day 7) and on Day 28 for the End-of-Study (EOS) Visit.

To assess safety and tolerability, subjects will undergo physical examinations (PE; including vital sign measurements), AE assessments, concomitant medication assessments, safety laboratory testing and Electrocardiogram (EKGs - completed locally), and other testing as per local custom.

2.2 Objectives

2.2.1 Primary objective

The primary objective of the study will be to evaluate the safety and tolerability of single and multiple ascending doses of rhu-pGSN administered by once-daily intravenous (IV) push to hospitalized subjects with a primary admitting diagnosis of CAP.

2.2.2 Secondary objectives

The secondary objective of the study will be to characterize the PK profile of rhu-pGSN after single or multiple IV doses

2.2.3 Exploratory objective.

The exploratory objectives of the study will be to investigate the following:

To assess the quantitative relationship of pGSN levels at baseline with clinical outcomes, changes in prognostic indices and inflammatory biomarkers, and etiologic pathogen type.

To assess the relationship between rhu-pGSN dose and clinical response and changes in surrogate biomarkers of efficacy.

2.2.4 Immunogenicity objective.

The immunogenicity objective of the study will be to investigate the post-treatment development of antibodies against rhu-pGSN by Day 28.



2.3 Sample Size

The sample size of N=6 rhu-pGSN recipients per dose level and combined placebo in the SD and MAD portions of the trial were chosen based on limiting exposure to pGSN in this initial study in the current development program. The sample sizes in this trial have the following properties in relation to interpretation of Adverse Events (AEs) incidence rates (Table 1).

Table 1 presents the Minimum Sample Size such that there is 90% probability of observing at least 1 AE of a certain type if the TRUE underlying AE rate.

Table 1: Minimum Sample Size Calculations

Sample Size TRUE underlying AE rate

6 (each pGSN dose level) 32% 8 (pooled placebo) 21% 24 (pooled pGSN) 10%

With each sample size presented in the table above, if zero AEs of a certain type are observed, one could be "90% confident" the TRUE underlying rate for that AE is at most the rate indicated above.

2.4 Randomization

Following screening, subjects qualified for study entry will be randomized to receive rhu-pGSN or placebo during the treatment period. Randomization will be done centrally using the Interactive web response system (IWRS). All eligible subjects will be assigned a randomization number.

There will be 1 single dose cohort (Cohort 1) and 3 multiple dose cohorts (Cohorts 2, 3 and 4). Eight subjects will be sequentially randomized to each cohort for a total number randomized of 32 subjects.

Subjects will be randomized in a 3:1 ratio to rhu-pGSN or placebo (6 rhu-pGSN subjects:2 placebo subjects).

The investigational site team and the subject will be kept blinded to the treatment allocation of each participant. Only the designated pharmacist(s) will be unblinded to the treatment allocation. The unblinded pharmacist will utilize the IWRS system to randomly assign a treatment allocation. The treatment allocation will be available to the unblinded pharmacist(s).



3. STATISTICAL CONSIDERATIONS

Data will be handled and processed per the sponsor’s representative (Novotech) Standard Operating Procedures (SOPs), which are written based on the principles of good clinical practice (GCP).

All data collected on the eCRFs will be presented in the data listings and will be listed and sorted by SD/MAD, treatment, subject number and visit, where applicable. All summaries will present the data by SD/MAD (apart from PK summaries), treatment group and overall (total subjects), as applicable. In addition, all placebo subjects will be combined into a single placebo group for purposes of summarizing the data.

Continuous variables: Descriptive statistics will include the number of non-missing values (N), mean, standard deviation (SD*), median, minimum, maximum.

The minimum and maximum values will be displayed to the same decimal precision as the source data, the arithmetic mean, SD* and median values will be displayed to one more decimal than the source data for the specific variable.

The appropriate precision for derived variables will be determined based on the precision of the data on which the derivations are based, and statistics will be presented in accordance with the abovementioned rules.

PK data: For PK data the arithmetic mean, standard deviation, median, minimum, maximum, coefficient of variation (CV%), geometric mean and geometric coefficient of variation (geo CV%) values will be presented. For the ratio of concentration data to the (within 30 minutes) pre-dose concentration on Day 1, the ln(SD*) will also be presented.

Categorical variables: Descriptive statistics will include frequency counts and percentages per category. Percentages will be rounded to one decimal place, with the denominator being the number of subjects in the relevant population with non-missing data, unless otherwise specified.

Time to Event Analysis: Through the Kaplan-Meier method, nonparametric estimates of the survivor function will be represented by quartile estimates (Q1, Median and Q3) along with 95 CIs. Product limit estimates will be presented as part of appendices to the study outputs (SAS output).

Imputation: No missing data will be imputed.

Baseline: Baseline values will be defined as the last valid, non-missing observation for each subject prior to the first dose of study medication. For the PK analysis, baseline will be defined as the pre-dose value for each study day.

Repeat assessments (Safety): No repeat assessments will be included in summary presentations (Tables, Figures). Only the original values will be used in summary presentations. All repeat assessments captured in the Electronic Data Capture (EDC) system will be presented in the data listings.

Assessment windows: All assessments will be included in the data listings and no visit windows will be applied to exclude assessments that were performed outside of the protocol specified procedure windows.

Date and time display conventions: The following display conventions will be applied in all outputs where dates and/or times are displayed:

Date only: DDMMMYYYY

Date and time: DDMMMYYYY /HH:MM



If only partial information is available, unknown components of the date or time will be presented as ‘NK’ (not known), i.e., ‘2016-NK-NK’. Times will be reported in military time.

In the summary tables and figures, treatment groups will be summarized separately for SD/MAD, each cohort, combined placebo and overall (all subjects). Study outcomes will be summarized as follows:

For each active dose level (overall):

SD Phase:

rhu-pGSN 6 mg/kg

Placebo

Overall

MAD Phase

rhu-pGSN 6 mg/kg

rhu-pGSN 12 mg/kg

rhu-pGSN 24 mg/kg

Combined Active

Combined Placebo

Overall



4. ANALYSIS POPULATIONS

In this study, four analysis populations are defined: Intention-to-treat (ITT), Safety, Pharmacokinetic and the Per Protocol populations (PP).

Furthermore, any additional exploratory analysis not identified in the SAP will be identified in the final CSR as exploratory post hoc analyses. This may include the addition of additional study populations or subgroups of interest.

The number and percentage of subjects in each analysis population will be summarized.

4.1 Population Descriptions

4.1.1 Intention-to-treat (ITT) population

The ITT population will be defined as all randomized subjects. Subjects will be analyzed per the randomized treatment they received if different from the actual treatment received.

All disposition, demographic and pharmacodynamic (PD) analyses will be based on the ITT population. All listings will be presented by the ITT population.

4.1.2 Safety population

The safety population will be defined as all enrolled subjects who received at least one dose of the study drug and will be based on actual treatment received.

If the safety population differs from the ITT population in that subjects received a different treatment to that they were randomized, or did not receive treatment whatsoever after randomization, the demographic and pharmacodynamic analyses will be repeated for the safety population.

All safety analyses will be based on the safety population.

4.1.3 Pharmacokinetic (PK) population

The PK population will comprise all subjects in the safety population who provide adequate PK samples to calculate the PK parameters. Subjects with important protocol deviations will be assessed on a subject-by-subject basis for inclusion in the PK Population. The PK analysis will be conducted using the Pharmacokinetic population.

4.1.4 Per Protocol (PP) population

The PP population will comprise all subjects in the safety population excluding subjects who missed doses and/or randomly discontinued the study before the primary Day 7 Visit. Furthermore, subject that had any relevant important protocol deviations will be excluded from the PP population.



5. PROTOCOL DEVIATIONS

In case protocol deviations/violations are reported, all protocol deviations/violations will be listed for each subject in the by-subject data listings. Prior to database lock and during the blinded review of database, all protocol deviations/violations will be reviewed and assigned a status of important or not.

Important protocol deviations/violations may include the following, depending on the timing and nature of the deviation:

INFORMED CONSENT DEVIATION: Subject not consented prior to study procedures being performed or subject not re-consented to study at next scheduled study visit following local approval of an updated PIS-CF.

ENTRY DEVIATION: Subject enrolled in violation of eligibility criteria.

WITHDRAWAL DEVIATION: Subject developed withdrawal criteria during the study, but were not withdrawn.

DOSING DEVIATION: Subject received the wrong treatment or incorrect dose of investigational product or comparator; Subject received treatment at incorrect timepoint in study; Subject received treatment that had not been stored per protocol.

OPERATIONAL DEVIATION: Informed consent deviations (other than consent not being obtained prior to study entry, which would be considered an Entry Deviation), IRB/IEC expired approval, significant visit window deviations, or other issues that may significantly impact subject safety or data integrity.



6. SUBJECT DISPOSITION

Outcomes will be summarized by the treatment groups as specified in section 3.

6.1.1 Subject disposition

Subject disposition will be summarized using counts and percentages and will be based on the ITT Population. The number of screened subjects, number and percentage of randomized subjects, subjects discontinued from the study as well as the primary reason for discontinuation will also be summarized.

All disposition information collected will be listed together with the date that the subject provided informed consent and the date and time of the first study drug administration. If the there is a difference between the ITT, Safety populations or the PP population, the disposition summary tables will be repeated for that population.

6.1.2 Analysis Populations

The number of subjects included in of each of the defined analysis populations will be summarized using counts and percentages and will be based on the ITT Population.

In addition, the inclusion/exclusion of each subject into/from each of the defined analysis populations will be listed.



7. DEMOGRAPHIC AND BASELINE INFORMATION

Demographic and baseline body measurements will be summarized using the ITT Population and may be repeated for the safety population and per protocol populations if different from the ITT population.

All information will be presented by the treatment groups as specified in section 3.

7.1 Demographics

7.1.1 Definition of variables

Age (years);

Sex;

Child Bearing Potential;

Method of Birth Control;

Race;

Height (cm);

Weight (kg);

7.1.2 Biostatistical methods

Quantitative and categorical summaries will be presented for demographic variables at the screening visit.

A by-subject data listing for demographic and baseline characteristics will be generated.

7.2 Medical history

Past medical history will be coded using the Medical Dictionary for Regulatory Activities, (MedDRA - latest version), and will be presented in the by-subject data listings including the MedDRA codes.

7.3 Pregnancy Test (Serum and Urine)

Pregnancy test results will be included in the by-subject data listings. This includes the pregnancy test results at Screening and Day 28/End of Study.

7.4 Serology

The following viral detection results (serologies) at Screening will be listed for each subject when available: Hepatitis B, Hepatitis C and HIV status.

7.5 Other baseline characteristics

Confirmation of CAP (both clinical and radiographic) will be presented in the by-subject data listings.



8. STUDY DRUG ADMINISTRATION

Study drug administration results will be presented using the ITT Population.

A by-subject data listing will be generated for study medication administration. These listings will include randomized dose assignment, Date/Time of Injection, Study Drug Administered (mL), duration of administrations, reason whole study drug dose was not administered, injection interruptions, re-start and reason for any interruptions. Subjects who receive the wrong IP (rhu-pGSN vs. placebo) will be flagged.



9. PHARMACOKINETICS (PK)

All PK summary tables and figures will be based on the PK Population. All listings will be based on the Safety Population (Actual Treatment). All analyses will be done by treatment group.

For the 1 dose in the SD arm and the first 2 doses in the MAD arms, blood will be drawn within 30 minutes pre-dose, and 5-10 minutes after the end of administration, as well as 2, 8, 12 and/or 16, and 24 hours after the end of administration (± 30 minutes) for analysis. Identical PK sampling is encouraged on Day 3 where feasible (but not required) in the multiple-dose arms.

In this section (section 9):

The rhu-pGSN treatment group will be referred to the Active treatment group.

Exogenous pGSN concentrations will be referred to as rhu-pGSN concentrations.

Endogenous pGSN + Exogenous pGSN (total) will be referred to as pGSN

9.1 Definition of variables

The following PK parameters for pGSN will be estimated For Day 1(SD/MAD), Day 2 (MAD) and Day 3 (MAD). PK Parameters will only be calculated for the Active (rhu-pGSN) treatment group. No PK parameters will be calculated for the Placebo treatment group:

Day 1: SD/MAD & Day 2/3: MAD

AUC0-t The area under the plasma concentration-time curve, from time 0 (time of dosing) to the last time point (24 hours) with measurable analyte concentration, calculated by the log down, linear up trapezoidal method.

AUC0-t will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.

AUC0-8 The area under the plasma concentration-time curve, from time 0 (time of dosing) to the 8 hours concentration, calculated by the log down, linear up trapezoidal method.

AUC0-8 will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.

AUC0-inf The area under the plasma concentration-time curve from time 0 extrapolated to infinity. AUC0-inf is calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant (kel).

Cmax Maximum observed concentration.

Cmax will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.

Tmax Time to maximum observed drug concentration. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value.



kel Apparent terminal elimination rate constant calculated by linear regression of the terminal linear portion of the log concentration vs. time curve.

t½ Apparent elimination half-life, calculated as ln(2)/kel

%AUCext Percentage of the extrapolated area under the plasma concentration-time curve, calculated as 100% * [AUC0-inf - AUC0-t]/ AUC0-inf

CL/F Apparent clearance calculated as Dose/AUC0-inf.

Vz/F Apparent volume of distribution at the terminal phase, calculated as Dose/ (kel × AUC0-inf).

DN_Cmax Dose-normalized Cmax, calculated as Cmax divided by dose

DN_Cmax will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose day 1 and the double-delta method..

DN_AUC0-inf Dose-normalized AUC0-inf, calculated as AUC0-inf divided by dose

DN_AUC0-t Dose-normalized AUC0-t, calculated as AUC0-t divided by dose

DN_AUC0-t will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.

DN_AUC0-8 Dose-normalized AUC0-24, calculated as AUC0-24 divided by dose

DN_AUC0-8 will additionally be calculated for the estimated rhu-pGSN profile for both the change from pre-dose on each study day and the double-delta method.

9.2 Biostatistical methods

Plasma pGSN

Individual plasma pGSN concentrations will be summarized by nominal sampling time.

Plasma pGSN concentrations that are below the quantitation limit (BQL) will be set to 0 if before the first quantifiable concentration, and to ½ the lower level of quantification elsewhere for calculation of summary statistics for concentration data at each time point.

The actual blood sampling dates and times relative to dosing time will be listed by subject and nominal sampling time, with time deviations calculated for all subjects with available plasma concentration data, including subjects excluded from the PK Population.

Individual (for each subject) and mean plasma pGSN concentration over time will be displayed graphically in linear and semi-logarithmic plot of pGSN concentration versus time. The actual collection time will be used for individual plasma pGSN concentration curve and the nominal time will be used for plot of mean plasma pGSN concentration curve.

Plasma concentrations vs. time data will be analyzed using validated PK software (Phoenix WinNonlin version 6.3 or higher), by standard non-compartmental model. Actual collection time will be used in the calculation of plasma PK parameters. For the calculation of the PK parameters, all plasma concentrations that are BLQ prior to the first measurable



concentration will be set to ½ the lower level of quantification. The BLQ values that are between measurable concentrations will be set to ½ LLOQ. The BLQ values that occur at the end of the profile (after the last quantifiable concentration) will also be set to ½ the lower level of quantification.

Ratio of Plasma pGSN

For subjects that do not have quantifiable pre-dose concentration values on each day, the pre-dose value will be set to ½ lower limit of quantification (LLQ).

Individual plasma pGSN: Day 1, 2 and Day 3 pGSN concentration ratios from each day’s pre-dose will be summarized by nominal sampling time.

Plasma pGSN concentrations that are below the quantitation limit (BQL) will be set to ½ the lower level of quantification post dose for calculation of summary statistics for concentration ratio data at each time point.

Ratio of Pre-dose and Placebo Adjusted Plasma pGSN

For the active treatment groups, plasma concentration of pGSN will further be evaluated (adjusted) in terms of the mean Placebo pGSN at each time point as well as the pre-dose (baseline value) for each study day:

Pre-dose values on each study day will be presented as recorded;

Pre-dose values on each study day that are BLQ will be set to ½ LLQ;

Subsequent BLQ values (post the first quantifiable concentration on each day) will be set to ½ LLQ.

Pre-dose and Placebo Adjusted Concentration

= (Active Treatment Group natural log Concentration on Day z at Time Point y – Day z Pre-dose natural log Concentration) - (Placebo Treatment Group natural log Concentration on Day z at Time Point y – Placebo Day z Pre-dose natural log Concentration) [results will be back-transformed to the ratio of ratios scale.]

Baseline and Placebo corrected Individual plasma pGSN concentrations will be summarized by nominal sampling time.

Analysis of Estimated rhu-pGSN

This analysis will exclude the placebo treatment group:




Estimated rhu-pGSN concentration

= concentration on Day z at Time Point y – Day z Pre-dose concentration

Individual estimated rhu-pGSN concentrations will be summarized by nominal sampling time. Geometric summary statistics will not be calculated for estimated rhu-pGSN concentrations, as these values could be lower than or equal to 0.

Estimated Individual (for each subject) and mean estimated plasma rhu-pGSN concentration over time will be displayed graphically in linear plots of estimated rhu-pGSN concentration versus time. The actual collection time will be used for individual estimated plasma rhu-pGSN concentration curve and the nominal time will be used for plot of mean estimated plasma rhu-pGSN concentration curve.



Estimated plasma concentrations vs. time data will be analyzed using SAS software. Actual collection time will be used in the calculation of plasma PK parameters. The following parameters (including dose normalized parameters) will be calculated for each study day:

AUC0-t

AUC0-8h

Cmax

Double Delta Analysis of Estimated rhu-pGSN




Estimated rhu-pGSN will be calculated as follows:

= (Active Treatment Group Concentration on Day z at Time Point y – Day z Pre-dose Concentration) - (Mean Placebo Treatment Group Concentration on Day z at Time Point y – Mean Placebo Day z Pre-dose Concentration)

Estimated rhu-pGSN concentrations will be summarized by nominal sampling time. Geometric summary statistics will not be calculated for estimated rhu-pGSN concentrations, as these values could be lower than or equal to 0.

Estimated Individual (for each subject) and mean estimated plasma rhu-pGSN concentration over time will be displayed graphically in linear plots of estimated rhu-pGSN concentration versus time. The nominal time will be used for individual estimated plasma rhu-pGSN concentration curve and the nominal time will be used for plot of mean estimated plasma rhu-pGSN concentration curve.

Estimated rhu-pGSN plasma concentrations vs. time data will be analyzed using SAS software. Nominal time will be used in the calculation of plasma PK parameters. The following parameters (including dose normalized parameters) will be calculated for each study day:

AUC0-t

AUC0-8h

Cmax



10. PHARMACODYNAMICS (EFFICACY)

All PD summary tables, figures and listings will be based on the ITT Population. All analysis will be done by study part (SD/MAD) by each treatment group.

As a sensitivity analysis, the analysis will be repeated based on the PP population.

10.1 Definition of variables

The following biomarkers will be analyzed:

Procalcitonin;

pGSN;

TNFα;

TGFβ;

IL1β;

IL1ra;

IL2;

IL4;

IL6;

IL10;

IL17a.`

10.2 Biostatistical methods

Biomarker will be summarized via counts and percentages of subjects for categorical variables, and by summary statistics for baseline, each observed time point, and ratio from baseline at each observed time point for continuous variables (as for the PK analysis with the exception of CV% and Geometric CV%) by treatment group and overall.



11. SAFETY

Safety endpoints will be analyzed using the Safety Population. All information will be presented by study part, for each treatment group and overall.

11.1 Adverse Events


Adverse event (AE)

Serious adverse event (SAE)

Treatment emergent adverse event (TEAE)

AEs and SAEs are defined in the study protocol. TEAEs are defined as adverse events that occurred or worsened following the first administration of study medication. Adverse events that have missing onset dates will be considered treatment-emergent, unless the stop date is known to be prior to the first administration of the study medication.

11.1.2 Biostatistical methods

All AEs will be coded using MedDRA.

All AE summaries will be restricted to TEAEs only. Summary tables will include the number of subjects (%) experiencing an event and the number of events. Subjects will be counted only once at each system organ class (SOC) and preferred term (PT) level of summary.

The TEAE summaries will include:

TEAE summary by SOC and PT

TEAE summary of serious events by SOC and PT

TEAE summary of deaths by SOC and PT

TEAE summary by severity (NCI-CTCAE) by SOC and PT

TEAE summary by causality to Study Drug by SOC and PT

TEAE summary by causality to Study Procedure by SOC and PT

TEAE summary of events leading to treatment discontinuation (Drug withdrawn) by SOC and PT

All AEs will be listed and will include verbatim term, PT, SOC, treatment, severity, causality, seriousness, and action taken with regards to the study drug. Separate listings will be created for SAEs, deaths and events leading to treatment discontinuation (Drug withdrawn).

Overall survival (time to death in days) will be analyzed through Kaplan-Meier methods and censored at the time of the study exit visit. Date of death will be taken as the SAE end date for which the outcome is stated to be fatal. Overall survival (days) = Date of event outcome of death/ Date of study exit - Date of first study drug administration + 1.



11.2 Safety Laboratory Assessments

Blood samples will be collected at the time points specified in the Schedule of Events (refer to the Protocol) to conduct Complete blood count (CBC), Coagulation and Comprehensive Metabolic Profile analyses.


The following tests will be performed within each of the specified test panels:

Complete blood count (CBC):

Hematocrit (HCT);

Hemoglobin (HGB);

Red Blood Cells (RBC)

White Blood Cells (WBC) with differential (including Eosinophils (EOS), Neutrophils (NEUT), Basophils (BASO), Lymphocytes (LYM) and Monocytes (MONO);

Platelets (PLAT);

Reticulocyte count

Coagulation:

Prothrombin Time (PT) / International Normalized Ratio (INR);

Partial Thromboplastin Time (PTT).

Comprehensive Metabolic Profile:

Albumin (ALB)

Blood Urea Nitrogen (BUN)

Creatinine (CREAT)

C-Reactive Protein (CRP)

Lactate Dehydrogenase (LDH)

Creatine phosphokinase (CPK)

Alanine Aminotransferase (ALT)

Aspartate Aminotransferase (AST)

Total Bilirubin (BILI)

Alkaline Phosphatase (ALP)

Amylase

Lipase

11.2.2 Biostatistical Methods

All laboratory data collected at scheduled and unscheduled visits will be included in the listings, but only results collected as scheduled visits will be included in the summary tables.

Results for individual parameters may be reported in different units depending on the analyzing laboratory. If required, the results (and the corresponding normal range cut-off values) for individual parameters may be converted to International System of Units (S.I.) units to summarize the data.



For the all parameters where a unit value has been reported, the parameter names that will be used in the outputs will comprise of the test name and the unit of measure, for example, ‘Albumin (g/L)’. Parameters will be sorted alphabetically within tables and listings.

For all parameters where a normal range limit value is reported, the normal range will be derived based on the available lower and upper limit values and any reported mathematical symbols. If both a lower and upper limit value is available, the normal range will be presented as ‘(Lower, Upper)’.

The reported results for each parameter with a defined normal range will be classified (‘Low’, ‘Normal’, ‘High’) in relation to the defined normal range limits. If a result is equal to the normal range cut-off value, the result will be considered ‘Normal’.

The change from baseline values at each post-baseline visit will be calculated for all parameters with continuous results (except for specific gravity and pH).

The decimal precision for each parameter will be based on the maximum number of decimals to which the reported result or the normal range limits are presented to in the raw data. The results and normal ranges will be displayed to the same decimal precision in the listings.

If a result for a parameter that is normally considered continuous is reported as a range (i.e., the result for basophils is reported as ‘<0.01’ for a single time point), the result may be converted to a numeric value that is smaller than the reported result to contribute to the derivations and the summary statistics. Any conversion rules that are applied will be highlighted in the footnotes of the affected tables and listings. The original reported result value will however be included in the listing.

The laboratory result tables will present summary statistics for each laboratory parameter within the specific test panel. For each parameter, summaries will be presented for the baseline and each scheduled post-baseline visit. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit.

Additionally, counts (%) of number subjects with values out of normal range at each scheduled time point will also be presented along with shift tables that will represent the changes in normal range categories across post-baseline time points.

The listings of laboratory parameters will include all the information (fields) collected. In addition, the observations that are used as the baseline record (value) for each parameter will be flagged, and the change from baseline values at each post-baseline visit will be presented.

For all parameters, standardized values will be reported.



11.3 Vital Signs Measurements


The following vital signs measurements will be taken at the time points specified in the Schedule of Events (refer to the Protocol):

Heart Rate (beats/min);

Systolic blood pressure (SBP) (mmHg)

Diastolic blood pressure (DBP) (mmHg)

Respiratory rate (breaths/min)

Temperature (ºC)

Pulse Oximetry (%)

Overall Investigator Interpretation


All vital signs data collected at scheduled and unscheduled visits will be included in the listings, but only results collected as scheduled visits will be included in the summary tables.

The parameter names that will be used in the outputs will comprise of the test name and the unit of measure, for example, ‘Systolic Blood Pressure (mmHg)’. Parameters will be sorted in the order that the measurements were collected in on the Vital Signs eCRF page within the tables and listings.

The change from baseline to the pre-dose assessment at each post-baseline visit will be calculated for all parameters.

The decimal precision for each parameter will be based on the maximum number of decimals to which the results were reported on the eCRF.

Vital signs measurements will present summary statistics for the results at the baseline and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit.

The summary of overall interpretation results table will present counts and percentages for the reported results at baseline and each post-baseline visit/time point. Result categories will be ordered as ‘Normal’, ‘Abnormal not clinical significant (NCS)’ and ‘Abnormal clinical significant (CS)’.

The listings of vital signs measurements will include all the information collected. In addition, the observations that are used as the baseline record (value) for each parameter will be flagged, and the change from baseline values at each post-baseline visit will be presented.



11.4 12 - Lead Electrocardiogram (EKG)


The following EKG measurements will be taken at the time points specified in the Schedule of Events (refer to the Protocol):

Heart Rate (beats/min);

PR Interval (ms)

QRS Interval (ms)

QT Interval (sec)

QTcF Interval (ms) = QT interval /cube root of the RR interval

Overall Investigator Interpretation


All EKG data collected at scheduled and unscheduled visits will be included in the listings, but only results collected as scheduled visits will be included in the summary tables.

The parameter names that will be used in the outputs will comprise of the test name and the unit of measure, for example, ‘Heart Rate (beats/min)’. Parameters will be sorted in the order that the measurements were collected in on the EKG eCRF page within the tables and listings.

For study visits where, multiple EKG measurement are taken, the mean of the measurements will be summarized and the worst-case overall investigator interpretation for the multiple measurements will be presented.



EKG measurements will present summary statistics for the results at the baseline and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit.

The summary of overall interpretation results table will present counts and percentages for the reported results at baseline and each post-baseline visit/time point. Result categories will be ordered as ‘Normal’, ‘Abnormal NCS’ and ‘Abnormal CS’.

The listings of EKG measurements will include all the information collected and calculated (mean results). In addition, the observations that are used as the baseline record (value) for each parameter will be flagged, and the change from baseline values at each post-baseline visit will be presented.

11.5 Physical Examinations

Physical Examination assessments will be listed for all time points.

11.6 Outcome Prediction Models


The following outcome prediction models will be taken at the time points specified in the Schedule of Events (refer to the Protocol):

CURB-65 Score;



Pneumonia Severity Index (PSI) Score

Pneumonia Severity Index (PSI) Risk Class

SOFA Score

Mini-Mental State Exam (MMSE) Score


All outcome prediction model data collected at scheduled and unscheduled visits will be included in the listings, but only results collected as scheduled visits will be included in the summary tables.



Outcome prediction model scores will present summary statistics for the results at the baseline and each scheduled post-baseline visit for each of the parameters. In addition, summaries will be presented for the change from baseline values at each scheduled post-baseline visit.

The summary of PSI Risk Class will present counts and percentages for the reported results at baseline and each post-baseline visit/time point. Result categories will be ordered by risk class.

The listings of outcome prediction model data will include all the information collected. In addition, the observations that are used as the baseline record (value) for each parameter will be flagged, and the change from baseline values at each post-baseline visit will be presented.

11.7 Concomitant Medications

Concomitant and prior medications will be coded using World Health Organization Drug Dictionary (WHO-DD, September 2015).

Prior medications are defined as any medication where the use was stopped prior to the first administration of the study medication. Prior medications will be listed only.

Concomitant medications are defined as any medication (other than the study drug) that was used at least once after the first administration of the study medication. Medications that were stopped on the same date as the first study drug infusion will be analyzed as concomitant medications. If a clear determination cannot be made (partial medication end dates) the medication will be classified as concomitant.

Concomitant medications will be summarized by WHO-DD Anatomical Therapeutic Chemical (ATC) class Level 3, and preferred term using frequency counts and percentages by study part and treatment group. Subjects who take the same medication more than once will be counted only once for that preferred term. Subjects will also only be counted once for each ATC3 class, regardless of the number of medications they have taken within that class

11.8 Other safety evaluations

Hospitalization follow-up will be presented in by-subject listings by study part and treatment group. Length of stay in hospital defined as date and time of discharge or date of study exit if still hospitalized at the time of death or study exit (censored at 23:59) - date and time of Hospitalization admission due to CAP in hours, length of ICU stay and the period of intubation in days will be listed and presented through Kaplan-Meier (K-M) methods.



The length of stay in ICU and period of intubation analysis will be restricted to subjects that stayed in the ICU and were intubated. The event investigated will be the cessation of ICU stay and the cessation of intubation.



12. IMMUNOGENICITY ENDPOINTS

All Immunogenicity endpoints will be listed using the safety population by study part and treatment. Specimens from placebo recipients will serve as a negative control.

Antibodies against rhu-pGSN will be blindly assayed from frozen specimens to determine whether the investigational product induces an antibody response in recipients.



13. EXPLORATORY ENDPOINTS

Other analyses to be performed include:

Blood, sputum, and other cultures as clinically indicated (note that a sputum culture is mandatory if a sputum specimen can be obtained and blood cultures are strongly encouraged at entry into the study).

Sputum neutrophil elastase (where feasible at entry and near the conclusion of study therapy).

Exploratory endpoints will be listed only.



14. HANDLING OF MISSING DATA

Missing, unused, or spurious data will be handling in the following manner:

There will be no imputations or substitution made for missing PD or safety data points;

For the PK analyses, imputations will be made for missing data points. Please see section 9 for more detail.



15. CHANGES TO THE PLANNED ANALYSIS

No planned changes.



15.1 Final Analysis (End of Study)

The final analysis will be conducted after all subjects have completed the study, the clinical database has been locked and the analysis populations have been approved.

The final analysis will be based on the final version of the SAP. Any deviations from the planned analysis will be documented in the CSR.



16. SOFTWARE

The following software will be used to perform the statistical analyses:

SAS® Version 9.4 or higher (SAS Institute, Cary, North Carolina, USA).

The following software will be used to perform the PK analysis: Phoenix WinNonlin® version 6.3 or higher.

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Pro

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file

Shi

fts fr

om B

asel

ine

(Low

, Nor

mal

, Hig

h)

Saf

ety

14.3

.4.3

.2.2

M

AD

: Sum

mar

y of

Com

preh

esiv

e M

etab

olic

Pro

file

Shi

fts fr

om B

asel

ine

(Low

, Nor

mal

, Hig

h)

Saf

ety

14.3

.4.4

.1

SD

: Sum

mar

y of

Vita

l Sig

ns (

Sum

mar

y of

Act

ual a

nd C

hang

e fr

om B

asel

ine

Val

ues)

by

Tim

epoi

nt

Saf

ety

14.3

.4.4

.2

MA

D: S

umm

ary

of V

ital S

igns

(S

umm

ary

of A

ctua

l and

Cha

nge

from

Bas

elin

e V

alue

s) b

y T

imep

oint

S

afet

y 14

.3.4

.5.1

S

D: S

umm

ary

of V

ital S

igns

Inte

rpre

tatio

n by

Tim

epoi

nt

Saf

ety

14.3

.4.5

.2

MA

D: S

umm

ary

of V

ital S

igns

Inte

rpre

tatio

n by

Tim

epoi

nt

Saf

ety

14.3

.4.6

.1

SD

: Sum

mar

y of

Mea

n E

KG

(S

umm

ary

of A

ctua

l and

Cha

nge

from

Bas

elin

e V

alue

s) b

y T

imep

oint

S

afet

y 14

.3.4

.6.2

M

AD

: Sum

mar

y of

Mea

n E

KG

(S

umm

ary

of A

ctua

l and

Cha

nge

from

Bas

elin

e V

alue

s) b

y T

imep

oint

S

afet

y

Pro

toco

l Num

ber:

BT

-201

03 D

ecem

ber

2018

D

ocum

ent s

tatu

s: F

inal

SA

P V

ersi

on 2

.0 A

men

dmen

t 1.0

N

ovot

ech

- S

tric

tly C

onfid

entia

l

Pag

e 38

of 4

4

No

. T

itle

A

na

lys

is

Po

pu

lati

on

14.3

.4.7

.1

SD

: Sum

mar

y of

EK

G In

terp

reta

tion

(Wor

st)

by T

imep

oint

S

afet

y 14

.3.4

.7.2

M

AD

: Sum

mar

y of

EK

G In

terp

reta

tion

(Wor

st)

by T

imep

oint

S

afet

y 14

.3.4

.8.1

S

D: S

umm

ary

of C

UR

B-6

5 S

core

(Sum

mar

y of

Act

ual a

nd C

hang

e fr

om B

asel

ine

Val

ues)

by

Tim

epoi

nt

Saf

ety

14.3

.4.8

.2

MA

D: S

umm

ary

of C

UR

B-6

5 S

core

(S

umm

ary

of A

ctua

l and

Cha

nge

from

Bas

elin

e V

alue

s) b

y T

imep

oint

S

afet

y 14

.3.4

.9.1

S

D: S

umm

ary

of P

SI S

core

(S

umm

ary

of A

ctua

l and

Cha

nge

from

Bas

elin

e V

alue

s) b

y T

imep

oint

S

afet

y 14

.3.4

.9.2

M

AD

: Sum

mar

y of

PS

I Sco

re (

Sum

mar

y of

Act

ual a

nd C

hang

e fr

om B

asel

ine

Val

ues)

by

Tim

epoi

nt

Saf

ety

14.3

.4.1

0.1

SD

: Sum

mar

y of

PS

I Ris

k C

lass

by

Tim

epoi

nt

Saf

ety

14.3

.4.1

0.2

MA

D: S

umm

ary

of P

SI R

isk

Cla

ss b

y T

imep

oint

S

afet

y 14

.3.4

.11.

1 S

D: S

umm

ary

of S

OF

A S

core

(S

umm

ary

of A

ctua

l and

Cha

nge

from

Bas

elin

e V

alue

s) b

y T

imep

oint

S

afet

y 14

.3.4

.11.

2 M

AD

: Sum

mar

y of

SO

FA

Sco

re (

Sum

mar

y of

Act

ual a

nd C

hang

e fr

om B

asel

ine

Val

ues)

by

Tim

epoi

nt

Saf

ety

14.3

.4.1

2.1

SD

: Sum

mar

y of

MM

SE

Sco

re (

Sum

mar

y of

Act

ual a

nd C

hang

e fr

om B

asel

ine

Val

ues)

by

Tim

epoi

nt

Saf

ety

14.3

.4.1

2.2

MA

D: S

umm

ary

of M

MS

E S

core

(S

umm

ary

of A

ctua

l and

Cha

nge

from

Bas

elin

e V

alue

s) b

y T

imep

oint

S

afet

y 14

.3.4

.13.

1 S

D: S

umm

ary

of H

ospi

taliz

atio

n S

afet

y 14

.3.4

.13.

2 M

AD

: Sum

mar

y of

Hos

pita

lizat

ion

Saf

ety

Pro

toco

l Num

ber:

BT

-201

03 D

ecem

ber

2018

D

ocum

ent s

tatu

s: F

inal

SA

P V

ersi

on 2

.0 A

men

dmen

t 1.0

N

ovot

ech

- S

tric

tly C

onfid

entia

l

Pag

e 39

of 4

4

18.

LIS

TIN

GS

No

. T

itle

A

na

lys

is

Po

pu

lati

on

16

.2.1

.2.1

S

D: S

ubje

ct D

ispo

sitio

n In

tent

-to-

Tre

at

16.2

.1.2

.2

MA

D: S

ubje

ct D

ispo

sitio

n In

tent

-to-

Tre

at

16.2

.2.1

S

D: P

roto

col D

evia

tions

In

tent

-to-

Tre

at

16.2

.2.2

M

AD

: Pro

toco

l Dev

iatio

ns

Inte

nt-t

o-T

reat

16

.2.3

.1

SD

: Ana

lysi

s P

opul

atio

ns

Inte

nt-t

o-T

reat

16

.2.3

.2

MA

D: A

naly

sis

Pop

ulat

ions

In

tent

-to-

Tre

at

16.2

.4.1

.1

SD

: Dem

ogra

phic

s an

d B

asel

ine

Cha

ract

eris

tics

Inte

nt-t

o-T

reat

16

.2.4

.1.2

M

AD

: Dem

ogra

phic

s an

d B

asel

ine

Cha

ract

eris

tics

Inte

nt-t

o-T

reat

16

.2.4

.2.1

S

D: V

iral S

erol

ogy

Inte

nt-t

o-T

reat

16

.2.4

.2.2

M

AD

: Vira

l Ser

olog

y In

tent

-to-

Tre

at

16.2

.4.3

.1

SD

: Med

ical

His

tory

In

tent

-to-

Tre

at

16.2

.4.3

.2

MA

D: M

edic

al H

isto

ry

Inte

nt-t

o-T

reat

16

.2.4

.4.1

S

D: P

regn

ancy

Tes

t Res

ults

In

tent

-to-

Tre

at

16.2

.4.4

.2

MA

D: P

regn

ancy

Tes

t Res

ults

In

tent

-to-

Tre

at

16.2

.4.5

.1

SD

: Con

firm

atio

n of

CA

P

Inte

nt-t

o-T

reat

16

.2.4

.5.2

M

AD

: Con

firm

atio

n of

CA

P

Inte

nt-t

o-T

reat

16

.2.4

.6.1

S

D: E

ligib

ility

Ass

essm

ent

Inte

nt-t

o-T

reat

16

.2.4

.6.2

M

AD

: Elig

ibili

ty C

riter

ia

Inte

nt-t

o-T

reat

16

.2.4

.7.1

S

D: P

rior

Med

icat

ions

In

tent

-to-

Tre

at

16.2

.4.7

.2

MA

D: P

rior

Med

icat

ions

In

tent

-to-

Tre

at

16.2

.5.1

.1

SD

: Ran

dom

izat

ion

Inte

nt-t

o-T

reat

16

.2.5

.1.2

M

AD

: Ran

dom

izat

ion

Inte

nt-t

o-T

reat

16

.2.5

.2.1

S

D: S

tudy

Dru

g A

dmin

istr

atio

n In

tent

-to-

Tre

at

16.2

.5.2

.2

MA

D: S

tudy

Dru

g A

dmin

istr

atio

n In

tent

-to-

Tre

at

16.2

.5.3

.1

SD

: Stu

dy D

rug

Inte

rrup

tion

Inte

nt-t

o-T

reat

16

.2.5

.3.2

M

AD

: Stu

dy D

rug

Inte

rrup

tion

Inte

nt-t

o-T

reat

16

.2.6

.1.1

S

D: I

ndiv

idua

l pG

SN

Pla

sma

Con

cent

ratio

ns (

unit)

In

tent

-to-

Tre

at

Pro

toco

l Num

ber:

BT

-201

03 D

ecem

ber

2018

D

ocum

ent s

tatu

s: F

inal

SA

P V

ersi

on 2

.0 A

men

dmen

t 1.0

N

ovot

ech

- S

tric

tly C

onfid

entia

l

Pag

e 40

of 4

4

No

. T

itle

A

na

lys

is

Po

pu

lati

on

16.2

.6.1

.2

MA

D: I

ndiv

idua

l pG

SN

Pla

sma

Con

cent

ratio

ns (

unit)

In

tent

-to-

Tre

at

16.2

.6.2

.1

SD

: Ind

ivid

ual E

stim

ated

Pla

sma

rhu-

pGS

N C

once

ntra

tions

(un

it)

Inte

nt-t

o-T

reat

16

.2.6

.2.2

M

AD

: Ind

ivid

ual E

stim

ated

Pla

sma

rhu-

pGS

N P

lasm

a C

once

ntra

tions

(un

it)

Inte

nt-t

o-T

reat

16

.2.6

.3.1

S

D: I

ndiv

idua

l pG

SN

Pla

sma

PK

Par

amet

ers

Inte

nt-t

o-T

reat

16

.2.6

.3.2

M

AD

: Ind

ivid

ual p

GS

N P

lasm

a P

K P

aram

eter

s by

Day

In

tent

-to-

Tre

at

16.2

.6.4

.1

SD

: Ind

ivid

ual E

stim

ated

Pla

sma

rhu-

pGS

N P

lasm

a P

K P

aram

eter

s In

tent

-to-

Tre

at

16.2

.6.4

.2

MA

D: I

ndiv

idua

l Est

imat

ed P

lasm

a rh

u-pG

SN

Pla

sma

PK

Par

amet

ers

by D

ay

Inte

nt-t

o-T

reat

16

.2.6

.5.1

S

D: A

nti-r

hu-p

GS

N A

ntib

odie

s In

tent

-to-

Tre

at

16.2

.6.5

.2

MA

D: A

nti-r

hu-p

GS

N A

ntib

odie

s In

tent

-to-

Tre

at

16.2

.6.6

.1

SD

: Bio

mar

kers

In

tent

-to-

Tre

at

16.2

.6.6

.2

MA

D: B

iom

arke

rs

Inte

nt-t

o-T

reat

16

.2.6

.7.1

S

D: S

putu

m a

nd B

lood

Cul

ture

In

tent

-to-

Tre

at

16.2

.6.7

.2

MA

D: S

putu

m a

nd B

lood

Cul

ture

In

tent

-to-

Tre

at

16.2

.7.1

.1

SD

: Adv

erse

Eve

nts

Inte

nt-t

o-T

reat

16

.2.7

.1.2

M

AD

: Adv

erse

Eve

nts

Inte

nt-t

o-T

reat

16

.2.7

.2.1

S

D: S

erio

us A

dver

se E

vent

s In

tent

-to-

Tre

at

16.2

.7.2

.2

MA

D: S

erio

us A

dver

se E

vent

s In

tent

-to-

Tre

at

16.2

.7.3

.1

SD

: Adv

erse

Eve

nts

Lead

ing

to S

tudy

Med

icat

ion

Dis

cont

inua

tion

Inte

nt-t

o-T

reat

16

.2.7

.3.2

M

AD

: Adv

erse

Eve

nts

Lead

ing

to S

tudy

Med

icat

ion

Dis

cont

inua

tion

Inte

nt-t

o-T

reat

16

.2.7

.4.1

S

D: O

vera

ll S

urvi

val

Inte

nt-t

o-T

reat

16

.2.7

.4.2

M

AD

: Ove

rall

Sur

viva

l In

tent

-to-

Tre

at

16.2

.8.1

.1.1

S

D: C

BC

In

tent

-to-

Tre

at

16.2

.8.1

.1.2

M

AD

: CB

C

Inte

nt-t

o-T

reat

16

.2.8

.1.2

.1

SD

: Abn

orm

al C

BC

In

tent

-to-

Tre

at

16.2

.8.1

.2.2

M

AD

: Abn

orm

al C

BC

In

tent

-to-

Tre

at

16.2

.8.2

.1.1

S

D: C

oagu

latio

n In

tent

-to-

Tre

at

16.2

.8.2

.1.2

M

AD

: Coa

gula

tion

Inte

nt-t

o-T

reat

16

.2.8

.2.2

.1

SD

: Abn

orm

al C

oagu

latio

n In

tent

-to-

Tre

at

16.2

.8.2

.2.2

M

AD

: Abn

orm

al C

oagu

latio

n In

tent

-to-

Tre

at

16.2

.8.3

.1.1

S

D: C

ompr

ehen

sive

Met

abol

ic P

rofil

e In

tent

-to-

Tre

at

16.2

.8.3

.1.2

M

AD

: Com

preh

ensi

ve M

etab

olic

Pro

file

Inte

nt-t

o-T

reat

Pro

toco

l Num

ber:

BT

-201

03 D

ecem

ber

2018

D

ocum

ent s

tatu

s: F

inal

SA

P V

ersi

on 2

.0 A

men

dmen

t 1.0

N

ovot

ech

- S

tric

tly C

onfid

entia

l

Pag

e 41

of 4

4

No

. T

itle

A

na

lys

is

Po

pu

lati

on

16.2

.8.3

.2.1

S

D: A

bnor

mal

Com

preh

ensi

ve M

etab

olic

Pro

file

Inte

nt-t

o-T

reat

16

.2.8

.3.2

.2

MA

D: A

bnor

mal

Com

preh

ensi

ve M

etab

olic

Pro

file

Inte

nt-t

o-T

reat

16

.2.9

.1

SD

: Vita

l Sig

ns

Inte

nt-t

o-T

reat

16

.2.9

.2

MA

D: V

ital S

igns

In

tent

-to-

Tre

at

16.2

.10.

1 S

D: E

KG

In

tent

-to-

Tre

at

16.2

.10.

2 M

AD

: EK

G

Inte

nt-t

o-T

reat

16

.2.1

1.1

SD

: Phy

sica

l Exa

min

atio

n In

tent

-to-

Tre

at

16.2

.11.

2 M

AD

: Phy

sica

l Exa

min

atio

n In

tent

-to-

Tre

at

16.2

.12.

1.1

SD

: Out

com

e P

redi

ctio

n M

odel

s C

UR

B-6

5 In

tent

-to-

Tre

at

16.2

.12.

1.2

MA

D: O

utco

me

Pre

dict

ion

Mod

els

CU

RB

-65

Inte

nt-t

o-T

reat

16

.2.1

2.2.

1 S

D: O

utco

me

Pre

dict

ion

Mod

els

PS

I (P

ort S

core

) In

tent

-to-

Tre

at

16.2

.12.

2.2

MA

D: O

utco

me

Pre

dict

ion

Mod

els

PS

I (P

ort S

core

) In

tent

-to-

Tre

at

16.2

.12.

3.1

SD

: Out

com

e P

redi

ctio

n M

odel

s S

OF

A S

core

In

tent

-to-

Tre

at

16.2

.12.

3.2

MA

D: O

utco

me

Pre

dict

ion

Mod

els

SO

FA

Sco

re

Inte

nt-t

o-T

reat

16

.2.1

2.4.

1 S

D: O

utco

me

Pre

dict

ion

Mod

els

MM

SE

Sco

re

Inte

nt-t

o-T

reat

16

.2.1

2.4.

2 M

AD

: Out

com

e P

redi

ctio

n M

odel

s M

MS

E S

core

In

tent

-to-

Tre

at

16.2

.13.

1 S

D: C

onco

mita

nt M

edic

atio

ns

Inte

nt-t

o-T

reat

16

.2.1

3.2

MA

D: C

onco

mita

nt M

edic

atio

n In

tent

-to-

Tre

at

16.2

.14.

1 S

D: H

ospi

taliz

atio

n F

ollo

w-U

p In

tent

-to-

Tre

at

16.2

.14.

2 M

AD

: Hos

pita

lizat

ion

Fol

low

-Up

Inte

nt-t

o-T

reat

Pro

toco

l Num

ber:

BT

-201

03 D

ecem

ber

2018

D

ocum

ent s

tatu

s: F

inal

SA

P V

ersi

on 2

.0 A

men

dmen

t 1.0

N

ovot

ech

- S

tric

tly C

onfid

entia

l

Pag

e 42

of 4

4

19.

FIG

UR

ES

No

. T

itle

A

na

lys

is

Po

pu

lati

on

14

.2.1

.1

Indi

vidu

al p

GS

N P

lasm

a C

once

ntra

tions

(ng

/mL)

(Li

near

sca

le)

by D

ay

PK

14

.2.1

.2

Indi

vidu

al p

GS

N P

lasm

a C

once

ntra

tions

(ng

/mL)

(S

emi-l

ogar

ithm

ic)

by D

ay

PK

14

.2.2

.1

Indi

vidu

al E

stim

ated

Pla

sma

rhu-

pGS

N P

lasm

a C

once

ntra

tions

(ng

/mL)

bas

ed o

n th

e D

oubl

e D

elta

Ana

lysi

s (L

inea

r sc

ale)

by

Day

P

K

14.2

.2.2

In

divi

dual

Est

imat

ed P

lasm

a rh

u-pG

SN

Pla

sma

Con

cent

ratio

ns (

ng/m

L) b

ased

on

the

Dou

ble

Del

ta A

naly

sis

(Lin

ear

scal

e)

by D

ay

PK

14.2

.3.1

M

ean

(+/-

SD

) pG

SN

Pla

sma

Con

cent

ratio

ns (

ng/m

L) (

Line

ar s

cale

) by

Day

P

K

14.2

.3.2

M

ean

(+/-

SD

) pG

SN

Pla

sma

Con

cent

ratio

ns (

ng/m

L) b

ased

on

Cha

nges

from

Pre

-Inj

ectio

n (

Line

ar s

cale

) by

Day

(S

emi-

loga

rithm

ic)

by D

ay

PK

14.2

.4.1

M

ean

(+/-

SD

) E

stim

ated

Pla

sma

rhu-

pGS

N P

lasm

a C

once

ntra

tions

(ng

/mL)

bas

ed o

n C

hang

es fr

om P

re-I

njec

tion

(Li

near

sc

ale)

by

Day

P

K

14.2

.4.2

M

ean

(+/-

SD

) E

stim

ated

Pla

sma

rhu-

pGS

N P

lasm

a C

once

ntra

tions

(ng

/mL)

bas

ed o

n th

e D

oubl

e D

elta

Ana

lysi

s (L

inea

r sc

ale)

by

Day

P

K

14.3

.1.1

S

D: K

apla

n-M

eier

Plo

t of O

vera

ll S

urvi

val T

ime

Saf

ety

14.3

.1.2

M

AD

: Kap

lan-

Mei

er P

lot o

f Ove

rall

Sur

viva

l Tim

e S

afet

y 14

.3.2

.1

SD

: Kap

lan-

Mei

er P

lot o

f Len

gth

of S

tay

in H

ospi

tal (

hour

s)

Saf

ety

14.3

.2.2

M

AD

: Kap

lan-

Mei

er P

lot o

f Len

gth

of S

tay

in H

ospi

tal (

hour

s)

Saf

ety

14.3

.3.1

S

D: K

apla

n-M

eier

Plo

t of D

urat

ion

of IC

U S

tay

Saf

ety

14.3

.3.2

M

AD

: Kap

lan-

Mei

er P

lot o

f Dur

atio

n of

ICU

Sta

y S

afet

y 14

.3.4

.1

SD

: Kap

lan-

Mei

er P

lot o

f Dur

atio

n of

Intu

batio

n S

afet

y 14

.3.4

.2

MA

D: K

apla

n-M

eier

Plo

t of D

urat

ion

of In

tuba

tion

Saf

ety

Pro

toco

l Num

ber:

BT

-201

03 D

ecem

ber

2018

D

ocum

ent s

tatu

s: F

inal

SA

P V

ersi

on 2

.0 A

men

dmen

t 1.0

N

ovot

ech

- S

tric

tly C

onfid

entia

l

Pag

e 43

of 4

4

20.

AP

PE

ND

ICE

S

No

. T

itle

A

na

lys

is

Po

pu

lati

on

14

.3.3

.9.1

S

D: S

umm

ary

of O

vera

ll S

urvi

val

Saf

ety

14.3

.3.9

.2

MA

D: S

umm

ary

of O

vera

ll S

urvi

val

Saf

ety

14.3

.4.1

3.1

SD

: Sum

mar

y of

Hos

pita

lizat

ion

Saf

ety

14.3

.4.1

3.2

MA

D: S

umm

ary

of H

ospi

taliz

atio

n S

afet

y



21. REFERENCES

1) Clinical Study Protocol Amendment 1.0, 30 April 2018.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

1 o

f 82

BT

I-201

: Moc

k Ta

bles

: Tab

le o

f Con

tent

s Tables

Tabl

e 14

.1.1

.1 S

D: S

umm

ary

of S

ubje

ct E

nrolm

ent

and

Disp

osit

ion

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

6

Tabl

e 14

.1.1

.2 M

AD:

Sum

mary

of

Subj

ect

Enrol

ment

and

Dis

posi

tion

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 7

Ta

ble

14.1

.2.1

SD:

Summ

ary

of D

emog

raph

ics a

nd B

asel

ine

Char

acter

isti

cs ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 8

Tabl

e 14

.1.2

.2 M

AD:

Summa

ry o

f De

mogr

aphi

cs

and

Base

line

Cha

racte

rist

ics

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 10

Tabl

e 14

.2.1

.1 D

ay 1

: S

umma

ry o

f Pl

asma

pGSN

Con

cent

rati

ons

(unit

) by

Tim

epoi

nt ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

11

Tabl

e 14

.2.1

.2 D

ay 2

: S

umma

ry o

f Pl

asma

pGSN

Con

cent

rati

ons

(unit

) by

Tim

epoi

nt ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

13

Tabl

e 14

.2.1

.3 D

ay 3

: S

umma

ry o

f Pl

asma

pGSN

Con

cent

rati

ons

(unit

) by

Tim

epoi

nt ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

15

Tabl

e 14

.2.1

.4 D

ay 1

: S

umma

ry o

f Es

tima

ted P

lasm

a rh

u-pG

SN C

oncen

trat

ions

(un

it)

by Ti

mepo

int

......

......

......

......

......

......

......

......

......

......

.....

16

Tabl

e 14

.2.1

.5 D

ay 2

: S

ummary

of

Esti

mate

d P

lasm

a rh

u-pG

SN C

oncen

trat

ions

(un

it)

by Ti

mepo

int

......

......

......

......

......

......

......

......

......

......

.....

18

Tabl

e 14

.2.1

.6 D

ay 3

: S

umma

ry o

f Es

tima

ted P

lasm

a rh

u-pG

SN C

oncen

trat

ions

(un

it)

by Ti

mepo

int

......

......

......

......

......

......

......

......

......

......

.....

20

Tabl

e 14

.2.2

.1 D

ay 1

: S

umma

ry o

f Pl

asma

pGSN

PK

Para

mete

rs ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 21

Tabl

e 14

.2.2

.2 D

ay 2

: S

umma

ry o

f Pl

asma

pGSN

PK

Para

mete

rs ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 22

Tabl

e 14

.2.2

.3 D

ay 3

: S

umma

ry o

f Pl

asma p

GSN

PK

Para

mete

rs ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 23

Tabl

e 14

.2.3

.1 D

ay 1

: S

umma

ry o

f Es

tima

ted P

lasm

a rh

u-pG

SN P

K Par

amet

ers

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 24

Tabl

e 14

.2.3

.2 D

ay 2

: S

umma

ry o

f Es

tima

ted P

lasm

a rh

u-pG

SN P

K Par

amet

ers

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 25

Tabl

e 14

.2.3

.3 D

ay 3

: S

umma

ry o

f Es

tima

ted P

lasm

a rh

u-pG

SN P

K Par

amet

ers

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 26

Tabl

e 14

.2.4

.1 S

D: S

umm

ary

of P

D Pa

rame

ters

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 2

7 Ta

ble

14.2

.4.2

MAD

: Sum

mary

of

PD P

aram

eters

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 28

Tabl

e 14

.2.5

.1 S

D: S

umm

ary

of P

D Pa

rame

ters

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 2

9 Ta

ble

14.2

.5.2

MAD

: Sum

mary

of

PD P

aram

eters

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 30

Tabl

e 14

.3.1

.1 S

D: S

umm

ary

of C

onco

mita

nt Me

dica

tion

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

31

Tabl

e 14

.3.1

.2 M

AD:

Sum

mary

of

Prio

r an

d Con

comi

tant

Med

icat

ion

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 3

2 Ta

ble

14.3

.3.1

.1 S

D: Ov

eral

l Su

mmar

y of

Trea

tmen

t-Em

erge

nt A

dvers

e Ev

ents

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

33

Tabl

e 14

.3.3

.1.2

MAD

: O

vera

ll S

umma

ry o

f Tre

atme

nt-E

merg

ent

Adver

se E

vent

s ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

34

Tabl

e 14

.3.3

.2.1

SD:

Su

mmar

y of

Tre

atme

nt-Em

erge

nt A

dver

se E

vents

(Su

mmar

y by

SOC

, PT)

.....

......

......

......

......

......

......

......

......

......

......

......

......

.... 3

5 Ta

ble

14.3

.3.2

.2 M

AD: S

umma

ry o

f Tr

eatm

ent-E

merg

ent

Adve

rse

Event

s (S

umma

ry b

y SO

C, PT

) ...

......

......

......

......

......

......

......

......

......

......

......

......

.... 3

6 Ta

ble

14.3

.3.3

.1 S

D: Su

mmar

y of

Tre

atme

nt-Em

erge

nt D

eath

s (S

ummar

y by

SOC

, PT

) ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 37

Ta

ble

14.3

.3.3

.2 M

AD: S

umma

ry o

f Tr

eatm

ent-E

merg

ent

Deat

hs (

Summa

ry b

y SO

C, P

T) ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

38

Tabl

e 14

.3.3

.4.1

SD:

Su

mmar

y of

Ser

ious

Trea

tmen

t-Em

erge

nt A

dvers

e Ev

ents

(Su

mmar

y by

SOC,

PT)

.....

......

......

......

......

......

......

......

......

......

... 3

9 Ta

ble

14.3

.3.4

.2 M

AD: S

umma

ry o

f Se

riou

s Tre

atme

nt-E

merg

ent

Adver

se E

vent

s (S

umma

ry by

SOC

, PT

) ...

......

......

......

......

......

......

......

......

......

... 4

0 Ta

ble

14.3

.3.5

.1 S

D: Su

mmar

y of

Tre

atme

nt-Em

erge

nt A

dver

se E

vents

(Su

mmar

y by

SOC

, PT

and

NCI-CT

CAE

Grad

e)

......

......

......

......

......

.... 4

1 Ta

ble

14.3

.3.5

.2 M

AD: S

umma

ry o

f Tr

eatm

ent-E

merg

ent

Adve

rse

Event

s (S

umma

ry b

y SO

C, PT

and

NCI

-CTC

AE G

rade)

.....

......

......

......

......

.. 42

Ta

ble

14.3

.1.6

.1 S

D: Su

mmar

y of

Tre

atme

nt-Em

erge

nt A

dver

se E

vents

(Su

mmar

y by

SOC

, PT

and

Rela

tion

ship

to S

tudy

Dru

g)...

.....

43

Tabl

e 14

.3.3

.6.2

MAD

: S

umma

ry o

f Tr

eatm

ent-E

merg

ent

Adve

rse

Event

s (S

umma

ry b

y SO

C, PT

and

Rel

atio

nshi

p to

Stud

y Dr

ug)

.....

44

Tabl

e 14

.3.3

.7.1

SD:

Su

mmar

y of

Tre

atme

nt-Em

erge

nt A

dver

se E

vents

(Su

mmar

y by

SOC

, PT

and

Rela

tion

ship

to Stu

dy P

roce

dure

)...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 45

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

2 o

f 82

Tabl

e 14

.3.3

.7.2

MAD

: S

umma

ry o

f Tr

eatm

ent-E

merg

ent

Adve

rse

Event

s (S

umma

ry b

y SO

C, PT

and

Rel

atio

nshi

p to

Study

Proc

edur

e) ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 46

Tabl

e 14

.3.3

.8.1

SD:

Su

mmar

y of

Tre

atme

nt-Em

erge

nt A

dver

se E

vents

Lea

ding

to

Trea

tment

Dis

cont

inua

tion

(Sum

mary

by

SOC,

PT

) ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

47

Tabl

e 14

.3.3

.8.2

MAD

: S

umma

ry o

f Tr

eatm

ent-E

merg

ent

Adve

rse

Event

s Le

adin

g to

Tre

atmen

t Di

scon

tinu

atio

n (Su

mmar

y by

SOC

, PT

) ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

48

Tabl

e 14

.3.3

.9.1

SD:

Su

mmar

y of

Ove

rall

Surv

ival

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 4

9 Ta

ble

14.3

.3.9

.2 M

AD: S

umma

ry o

f Ov

eral

l Sur

viva

l ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

50

Tabl

e 14

.3.4

.1.1

.1 S

D:

Summ

ary

of C

BC (

Summa

ry o

f Ac

tual

and

Chan

ge f

rom

Base

line

Valu

es)

by T

imep

oint

.....

......

......

......

......

......

......

.. 51

Ta

ble

14.3

.4.1

.1.2

MAD:

Sum

mary

of

CBC

(Summ

ary

of A

ctua

l an

d Cha

nge

from

Bas

elin

e Val

ues)

by

Time

poin

t ...

......

......

......

......

......

......

.. 52

Ta

ble

14.3

.4.1

.2.1

SD:

Summ

ary

of C

BC S

hifts

fro

m Ba

seli

ne (

Low,

Norm

al,

High

) ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 53

Ta

ble

14.3

.4.1

.2.2

MAD:

Sum

mary

of

CBC

Shift

s fr

om B

asel

ine

(Low,

Nor

mal,

Hig

h) ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

54

Tabl

e 14

.3.4

.2.1

.1 S

D:

Summ

ary

of C

oagu

latio

n (S

umma

ry o

f Ac

tual

and

Chan

ge f

rom

Basel

ine

Valu

es)

by T

imepo

int

.....

......

......

......

. 55

Tabl

e 14

.3.4

.2.1

.2 M

AD:

Sum

mary

of

Coag

ulati

on (

Summ

ary

of A

ctual

and

Cha

nge

from

Base

line

Val

ues)

by

Timep

oint

......

......

......

.... 5

6 Ta

ble

14.3

.4.2

.2.1

SD:

Summ

ary

of C

oagu

latio

n Sh

ifts

fro

m Ba

selin

e (L

ow,

Norm

al,

High)

.....

......

......

......

......

......

......

......

......

......

......

......

......

.... 5

7 Ta

ble

14.3

.4.2

.2.2

MAD:

Sum

mary

of

Coag

ulati

on S

hift

s fr

om B

aseli

ne (

Low,

Nor

mal,

High

) ...

......

......

......

......

......

......

......

......

......

......

......

......

.... 5

8 Ta

ble

14.3

.4.3

.1.1

SD:

Summ

ary

of C

ompr

ehens

ive

Meta

boli

c Pr

ofile

(Su

mmar

y of

Act

ual a

nd C

hang

e fr

om B

aseli

ne V

alue

s) b

y Ti

mepo

int

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 59

Tabl

e 14

.3.4

.3.1

.2 M

AD:

Sum

mary

of

Comp

rehen

sive

Met

abol

ic P

rofil

e (S

umma

ry o

f Ac

tual

and

Chan

ge f

rom

Basel

ine

Valu

es)

by

Time

poin

t ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 6

0 Ta

ble

14.3

.4.3

.2.1

SD:

Summ

ary

of C

ompr

ehens

ive

Meta

boli

c Pr

ofile

Shi

fts

from

Bas

eline

(Lo

w, N

orma

l, H

igh)

......

......

......

......

......

.... 6

1 Ta

ble

14.3

.4.3

.2.2

MAD:

Sum

mary

of

Comp

rehen

sive

Met

abol

ic P

rofil

e Sh

ifts

fro

m Ba

selin

e (L

ow,

Norm

al,

High)

.....

......

......

......

......

.. 62

Ta

ble

14.3

.4.4

.1 S

D: Su

mmar

y of

Vit

al S

igns

(Sum

mary

of

Actu

al an

d Ch

ange

fro

m Ba

selin

e Va

lues

) by

Tim

epoin

t ...

......

......

......

......

.. 63

Ta

ble

14.3

.4.4

.2 M

AD: S

umma

ry o

f Vi

tal

Signs

(Su

mmar

y of

Act

ual a

nd C

hang

e fr

om B

aseli

ne V

alue

s) b

y Ti

mepoi

nt...

......

......

......

......

64

Tabl

e 14

.3.4

.5.1

SD:

Su

mmar

y of

Vit

al S

igns

Inte

rpre

tati

on b

y Tim

epoi

nt ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

65

Tabl

e 14

.3.4

.5.2

MAD

: S

umma

ry o

f Vi

tal

Signs

Int

erpr

etat

ion

by Ti

mepo

int

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 66

Tabl

e 14

.3.4

.6.1

SD:

Su

mmar

y of

Mea

n EK

G (Su

mmar

y of

Act

ual

and C

hang

e fr

om B

asel

ine V

alue

s) b

y Ti

mepo

int

......

......

......

......

......

......

67

Tabl

e 14

.3.4

.6.2

MAD

: S

umma

ry o

f Me

an E

KG (S

umma

ry o

f Ac

tual

and

Chan

ge f

rom

Base

line

Valu

es)

by T

imep

oint

......

......

......

......

......

.... 6

8 Ta

ble

14.3

.4.7

.1 S

D: Su

mmar

y of

EKG

Int

erpre

tati

on (

Wors

t) b

y Tim

epoi

nt ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

69

Tabl

e 14

.3.4

.7.2

MAD

: S

umma

ry o

f EK

G In

terpr

etat

ion

(Wor

st)

by Ti

mepo

int

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 70

Tabl

e 14

.3.4

.8.1

SD:

Su

mmar

y of

CUR

B-65

Scor

e(Su

mmar

y of

Act

ual a

nd C

hang

e fr

om B

aseli

ne V

alue

s) b

y Ti

mepoi

nt...

......

......

......

......

71

Tabl

e 14

.3.4

.8.2

MAD

: S

umma

ry o

f CU

RB-6

5 Sco

re (

Summ

ary

of A

ctual

and

Cha

nge

from

Base

line

Val

ues)

by

Timep

oint

......

......

......

.... 7

2 Ta

ble

14.3

.4.9

.1 S

D: Su

mmar

y of

PSI

Sco

re (S

umma

ry o

f Ac

tual

and

Chan

ge f

rom

Base

line

Valu

es)

by T

imep

oint

......

......

......

......

......

.... 7

3 Ta

ble

14.3

.4.9

.2 M

AD: S

umma

ry o

f PS

I Sc

ore (

Summ

ary

of A

ctua

l and

Cha

nge

from

Bas

eline

Val

ues)

by

Time

point

.....

......

......

......

......

.. 74

Ta

ble

14.3

.4.1

0.1

SD: S

umma

ry o

f PS

I Risk

Cl

ass

by T

imep

oint

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

75

Tabl

e 14

.3.4

.10.

2 MA

D:

Summ

ary

of P

SI R

isk C

lass

by

Time

poin

t ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

76

Tabl

e 14

.3.4

.11.

1 SD

: S

umma

ry o

f SO

FA S

core

(Sum

mary

of

Actu

al an

d Ch

ange

fro

m Ba

selin

e Va

lues

) by

Tim

epoin

t ...

......

......

......

......

.. 77

Ta

ble

14.3

.4.1

1.2

MAD:

Summ

ary

of S

OFA

Score

(Su

mmar

y of

Act

ual a

nd C

hang

e fr

om B

aseli

ne V

alue

s) b

y Ti

mepoi

nt...

......

......

......

......

78

Tabl

e 14

.3.4

.12.

1 SD

: S

umma

ry o

f MM

SE S

core

(Sum

mary

of

Actu

al an

d Ch

ange

fro

m Ba

selin

e Va

lues

) by

Tim

epoin

t ...

......

......

......

......

.. 79

Ta

ble

14.3

.4.1

2.2

MAD:

Summ

ary

of M

MSE

Score

(Su

mmar

y of

Act

ual a

nd C

hang

e fr

om B

aseli

ne V

alue

s) b

y Ti

mepoi

nt...

......

......

......

......

80

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

3 o

f 82

Tabl

e 14

.3.4

.13.

1 SD

: S

umma

ry o

f Ho

spit

aliza

tion

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 8

1 Ta

ble

14.3

.4.1

3.2

MAD:

Summ

ary

of H

ospi

taliz

atio

n ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

82

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

4 o

f 82

GEN

ERAL

CO

MM

ENTS

W

here

a c

ount

is 0

, the

per

cent

age

will

not

be

show

n (e

.g. 0

(0.0

%) w

ill b

e di

spla

yed

as 0

)

Unl

ess o

ther

wise

stat

es, p

aram

eter

s will

be

liste

d in

alp

habe

tical

ord

er

Pe

rcen

tage

s and

thei

r 95%

CI,

whe

re a

ppro

pria

te, w

ill b

e pr

esen

ted

to o

ne d

ecim

al p

lace

The

min

imum

and

max

imum

val

ues w

ill b

e pr

esen

ted

to th

e sa

me

num

ber o

f dec

imal

pla

ces a

s rec

orde

d in

the

elec

tron

ic C

ase

Repo

rt F

orm

(eCR

F)

M

ean,

med

ian,

and

SD

will

be

pres

ente

d to

one

mor

e de

cim

al p

lace

than

the

raw

dat

a

Perc

enta

ges w

ill b

e ro

unde

d to

one

dec

imal

pla

ce, w

ith th

e de

nom

inat

or b

eing

the

num

ber o

f sub

ject

s in

the

rele

vant

pop

ulat

ion

with

non

-miss

ing

data

, unl

ess

othe

rwise

spec

ified

Chan

ge fr

om B

asel

ine:

Ch

ange

from

Bas

elin

e w

ill b

e ca

lcul

ated

as:

U

nsch

edul

ed v

isits

will

be

excl

uded

from

sum

mar

y ta

bles

Nam

es a

nd o

rder

of T

reat

men

t Gro

ups

SD:

rh

u-pG

SN 6

mg/

kg;

Pl

aceb

o;

O

vera

ll.

MAD

: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Plac

ebo;

Ove

rall.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

5 o

f 82

N

ames

of v

isits

SD

:

Scre

enin

g

Day

1

Day

2

Day

3/4

Da

y 7

Da

y 14

Day

28 /

Early

Ter

min

atio

n (C

ombi

ned

visit

for s

afet

y an

d PD

)

MAD

: Sc

reen

ing

Da

y 1

Da

y 2

Da

y 3

Da

y 4

Da

y 7

Da

y 14

Day

28 /

Early

Ter

min

atio

n (C

ombi

ned

visit

for s

afet

y an

d PD

)

Colu

mn

wid

ths a

nd te

xt-w

rapp

ing

may

be

alte

red

in fi

nal o

utpu

t in

orde

r to

best

pre

sent

the

data

Foot

note

s may

be

adde

d/am

ende

d if

requ

ired

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

6 o

f 82

Table 14.1.1.1 SD: Summary of Subject Enrolment and Disposition

Protocol: BTI-201

Intent-to-Treat Population

rhu-pGSN

6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Number of Subjects Screened

xx

xx

xx

Number of Screening Failures1

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects Randomized

xx

xx

xx

Number of Subjects who Completed the Study

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects Discontinued

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Primary Reason for Discontinuation of Study

Due to Adverse Event

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Subject withdrew consent

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Investigator Decision

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Non-Compliance with the study procedures/protocol

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Any clinically significant change in subject’s medical condition

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Sponsor ended study

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Lost to follow-up

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Other

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects included in the ITT Population

x (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects included in the Safety Population

x (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects included in the PK Population

x (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects included in the PP Population

x (xx.x%)

xx (xx.x%)

xx (xx.x%)

1Percentages are based on number of subjects screened.

Clinical cut-off date: DDMMMYYYY

Program: filepath_name, Output: filepath_name (version x.x) Created: DDMMMYYYY HH:MM

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

7 o

f 82

Table 14.1.1.2 MAD: Summary of Subject Enrolment and Disposition

Protocol: BTI-201




Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.1.

1.1

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

8 o

f 82

Table 14.1.2.1 SD: Summary of Demographics and Baseline Characteristics

Protocol: BTI-201


rhu-pGSN

6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Age (years) at Screening

n

xx

xx

xx

Mean

xx.x

xx.x

xx.x

Median

xx.x

xx.x

xx.x

SD

x.x

x.x

xx.x

Minimum

xx

xx

xx

Maximum

xx

xx

xx

Sex n(%)

Female

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Male

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Race n(%)

Asian

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Pacific Islander

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Black or African

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Pacific Islander

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Aborigine/Torres Strait Islander

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

White

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Other

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Childbearing Potential n(%)*

Yes

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

No

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

*Percentages are based on the number of female participants.

SD: Standard Deviation



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

9 o

f 82

Table 14.1.2.1 SD: Summary of Demographics and Baseline Characteristics

Protocol: BTI-201


rhu-pGSN

6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Height (cm)

n

xx

xx

xx

Mean

xx.x

xx.x

xx.x

Median

xx.x

xx.x

xx.x

SD

x.x

x.x

xx.x

Minimum

xx

xx

xx

Maximum

xx

xx

xx

Weight (kg)

n

xx

xx

xx

Mean

xx.x

xx.x

xx.x

Median

xx.x

xx.x

xx.x

SD

x.x

x.x

xx.x

Minimum

xx

xx

xx

Maximum

xx

xx

xx

*Percentages are based on the number of female participants.

SD: Standard Deviation



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

10

of 8

2 Table 14.1.2.2 MAD: Summary of Demographics and Baseline Characteristics

Protocol: BTI-201



Program: filepath_name (version x.x), Output: filepath_name Created: DDMMMYYYY

Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.1.

2.1

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

11

of 8

2 Table 14.2.1.1 Day 1: Summary of Plasma pGSN Concentrations (unit) by Timepoint

Protocol: BTI-201

PK Population

Time Point

SD/MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

Placebo

(N=xx)

Actual

Value

Ratio

from Pre-

Injection

Ratio from

Pre-

Injection/

Placebo

Ratio from

Pre-

Injection

Actual

Value

Ratio

from Pre-

Injection

Ratio from

Pre-

Injection/

Placebo

Ratio from

Pre-

Injection

Actual

Value

Ratio

from Pre-

Injection

Pre-Injection

n

x

x

x

Mean

x.x

x.x

x.x

Median

x.x

x.x

x.x

SD

x.x

x.x

x.x

Minimum

x

x

x

Maximum

x

x

x

CV%

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

5 to 10 mins post

n

x

x

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

ln SD

x.x

x.x

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

….

SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%; BLQ: Below Limit of Quantification



Prog

ram

min

g N

ote:

Rep

eat f

or a

ll tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

12

of 8

2 Table 14.2.1.1 Day 1: Summary of Plasma pGSN Concentrations (unit) by Timepoint (continued)

Protocol: BTI-201

PK Population

Time Point

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Placebo

(N=xx)

Actual Value

Ratio from

Pre-Injection

Ratio from Pre-

Injection/

Placebo Ratio

from Pre-

Injection

Actual Value

Ratio

from Pre-Injection

Pre-Injection

n

x

x

Mean

x.x

x.x

Median

x.x

x.x

SD

x.x

x.x

Minimum

x

x

Maximum

x

x

CV%

x.x

x.x

GeoMean

x.x

x.x

GeoCV%

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

5 to 10 mins post

n

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

Maximum

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

ln SD

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

….




Prog

ram

min

g N

ote:

Rep

eat f

or a

ll tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

13

of 8


Protocol: BTI-201

PK Population

Time Point

MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

Placebo

(N=xx)

Actual

Value

Ratio

from Pre-

Injection

Ratio from

Pre-

Injection/

Placebo

Ratio from

Pre-

Injection

Actual

Value

Ratio

from Pre-

Injection

Ratio from

Pre-

Injection/

Placebo

Ratio from

Pre-

Injection

Actual

Value

Ratio

from Pre-

Injection

Pre-Injection

n

x

x

x

Mean

x.x

x.x

x.x

Median

x.x

x.x

x.x

SD

x.x

x.x

x.x

Minimum

x

x

x

Maximum

x

x

x

CV%

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

5 to 10 mins post

n

x

x

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

ln SD

x.x

x.x

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

….




Prog

ram

min

g N

ote:

Rep

eat f

or a

ll tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

14

of 8

2 Table 14.2.1.2 Day 2: Summary of Plasma pGSN Concentrations (unit) by Timepoint (continued)

Protocol: BTI-201

PK Population

Time Point

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Placebo

(N=xx)

Actual Value

Ratio from

Pre-Injection

Ratio from Pre-

Injection/

Placebo Ratio

from Pre-

Injection

Actual Value

Ratio

from Pre-Injection

Pre-Injection

n

x

x

Mean

x.x

x.x

Median

x.x

x.x

SD

x.x

x.x

Minimum

x

x

Maximum

x

x

CV%

x.x

x.x

GeoMean

x.x

x.x

GeoCV%

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

5 to 10 mins post

n

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

Maximum

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

ln SD

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

x (xx.x%)

….




Prog

ram

min

g N

ote:

Rep

eat f

or a

ll tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

15

of 8


Protocol: BTI-201

PK Population

Prog

ram

min

g N

ote:

Rep

eat T

able

14.

2.1.

2 fo

r Day

3.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

16

of 8

2 Table 14.2.1.4 Day 1: Summary of Estimated Plasma rhu-pGSN Concentrations (unit) by Timepoint

Protocol: BTI-201

PK Population

Time Point

SD/MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

Placebo

(N=xx)

Actual

Value

Change

from Pre-

Injection

(Change from

Pre-

Injection)-

(Mean Placebo

Change from

Pre-

Injection)

Actual

Value

Change

from Pre-

Injection

(Change from

Pre-

Injection)-

(Mean Placebo

Change from

Pre-

Injection)

Actual

Value

Change

from Pre-

Injection

Pre-Injection

n

x

x

x

Mean

x.x

x.x

x.x

Median

x.x

x.x

x.x

SD

x.x

x.x

x.x

Minimum

x

x

x

Maximum

x

x

x

CV%

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

5 to 10 mins post

n

x

x

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

….

SD: Standard Deviation; BLQ: Below Limit of Quantification



Prog

ram

min

g N

ote:

Rep

eat f

or a

ll tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

17

of 8

2 Table 14.2.1.4 Day 1: Summary of Estimated Plasma rhu-pGSN Concentrations (unit) by Timepoint (continued)

Protocol: BTI-201

PK Population

Time Point

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Placebo

(N=xx)

Actual Value

Change from

Pre-Injection

(Change from Pre-

Injection)-

(Mean Placebo

Change from Pre-

Injection)

Actual Value

Change

from Pre-Injection

Pre-Injection

n

x

x

Mean

x.x

x.x

Median

x.x

x.x

SD

x.x

x.x

Minimum

x

x

Maximum

x

x

CV%

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

5 to 10 mins post

n

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

Maximum

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

….




Prog

ram

min

g N

ote:

Rep

eat f

or a

ll tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

18

of 8


Protocol: BTI-201

PK Population

Time Point

MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

Placebo

(N=xx)

Actual

Value

Change

from Pre-

Injection

(Change from

Pre-

Injection)-

(Mean Placebo

Change from

Pre-

Injection)

Actual

Value

Change

from Pre-

Injection

(Change from

Pre-

Injection)-

(Mean Placebo

Change from

Pre-

Injection)

Actual

Value

Change

from Pre-

Injection

Pre-Injection

n

x

x

x

Mean

x.x

x.x

x.x

Median

x.x

x.x

x.x

SD

x.x

x.x

x.x

Minimum

x

x

x

Maximum

x

x

x

CV%

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

5 to 10 mins post

n

x

x

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

x (xx.x%)

….




Prog

ram

min

g N

ote:

Rep

eat f

or a

ll tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

19

of 8

2 Table 14.2.1.5 Day 2: Summary of Estimated Plasma rhu-pGSN Concentrations (unit) by Timepoint (continued)

Protocol: BTI-201

PK Population

Time Point

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Placebo

(N=xx)

Actual Value

Change from

Pre-Injection

(Change from

Pre-Injection)-

(Mean Placebo

Change from Pre-

Injection)

Actual Value

Change

from Pre-Injection

Pre-Injection

n

x

x

Mean

x.x

x.x

Median

x.x

x.x

SD

x.x

x.x

Minimum

x

x

Maximum

x

x

CV%

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

5 to 10 mins post

n

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

Maximum

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

BLQ

x (xx.x%)

x (xx.x%)

….




Prog

ram

min

g N

ote:

Rep

eat f

or a

ll tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

20

of 8


Protocol: BTI-201

PK Population

Prog

ram

min

g N

ote:

Rep

eat T

able

14.

2.1.

5 fo

r Day

3.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

21

of 8

2 Table 14.2.2.1 Day 1: Summary of Plasma pGSN PK Parameters

Protocol: BTI-201

PK Population

Parameter (unit)

SD/MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Placebo

(N=xx)

AUC0-t (unit)

n

x

x

x

x

Mean

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

Median

x

x

x

x

Maximum

x

x

x

x

CV%

x.x

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x

Cmax (unit)

n

x

x

x

x

Mean

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

Median

x

x

x

x

Maximum

x

x

x

x

CV%

x.x

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x

SD: Standard Deviation; GeoMean: Geometric Mean; GeoCV%: Geometric CV%



Prog

ram

min

g N

ote:

Rep

eat f

or a

ll PK

par

amet

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

22

of 8


Protocol: BTI-201

PK Population

Parameter (unit)

MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Placebo

(N=xx)

AUC0-t (unit)

n

x

x

x

x

Mean

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

Median

x

x

x

x

Maximum

x

x

x

x

CV%

x.x

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x

Cmax (unit)

n

x

x

x

x

Mean

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

Median

x

x

x

x

Maximum

x

x

x

x

CV%

x.x

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x




Prog

ram

min

g N

ote:

Rep

eat f

or a

ll PK

par

amet

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

23

of 8


Protocol: BTI-201

PK Population

Parameter (unit)

MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Placebo

(N=xx)

AUC0-t (unit)

n

x

x

x

x

Mean

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

Median

x

x

x

x

Maximum

x

x

x

x

CV%

x.x

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x

Cmax (unit)

n

x

x

x

x

Mean

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

Median

x

x

x

x

Maximum

x

x

x

x

CV%

x.x

x.x

x.x

x.x

GeoMean

x.x

x.x

x.x

x.x

GeoCV%

x.x

x.x

x.x

x.x




Prog

ram

min

g N

ote:

Rep

eat f

or a

ll PK

par

amet

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

24

of 8

2 Table 14.2.3.1 Day 1: Summary of Estimated Plasma rhu-pGSN PK Parameters

Protocol: BTI-201

PK Population

Parameter (unit)

SD/MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Change from

Pre-Injection

Double Delta

Analysis

Change from

Pre-Injection

Double Delta

Analysis

Change from

Pre-Injection

Double Delta

Analysis

AUC0-t (unit)

n

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x

Cmax (unit)

n

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x

SD: Standard Deviation;



Prog

ram

min

g N

ote:

Incl

ude

the

follo

win

g: P

K pa

ram

eter

s (in

clud

ing

dose

nor

mal

ized

para

met

ers)

:

A

UC

0-t

A

UC

0-8h

C m

ax

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

25

of 8


Protocol: BTI-201

PK Population

Parameter (unit)

MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Change from

Pre-Injection

Double Delta

Analysis

Change from

Pre-Injection

Double Delta

Analysis

Change from

Pre-Injection

Double Delta

Analysis

AUC0-t (unit)

n

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x

Cmax (unit)

n

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x




Prog

ram

min

g N

ote:

Incl

ude

the

follo

win

g: P

K pa

ram

eter

s (in

clud

ing

dose

nor

mal

ized

para

met

ers)

:

A

UC

0-t

A

UC

0-8h

C m

ax

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

26

of 8


Protocol: BTI-201

PK Population

Parameter (unit)

MAD

rhu-pGSN

6 mg/kg

(N=xx)

MAD

rhu-pGSN

12 mg/kg

(N=xx)

MAD

rhu-pGSN

24 mg/kg

(N=xx)

Change from

Pre-Injection

Double Delta

Analysis

Change from

Pre-Injection

Double Delta

Analysis

Change from

Pre-Injection

Double Delta

Analysis

AUC0-t (unit)

n

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x

Cmax (unit)

n

x

x

x

x

x

x

Mean

x.x

x.x

x.x

x.x

x.x

x.x

SD

x.x

x.x

x.x

x.x

x.x

x.x

Minimum

x.x

x.x

x.x

x.x

x.x

x.x

Median

x

x

x

x

x

x

Maximum

x

x

x

x

x

x

CV%

x.x

x.x

x.x

x.x

x.x

x.x




Prog

ram

min

g N

ote:

Incl

ude

the

follo

win

g: P

K pa

ram

eter

s (in

clud

ing

dose

nor

mal

ized

para

met

ers)

:

A

UC

0-t

A

UC

0-8h

C m

ax

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

27

of 8

2 Table 14.2.4.1 SD: Summary of PD Parameters

Protocol: BTI-201


Parameter

Visit

rhu-pGSN 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Actual Value

Ratio from

Baseline1

Actual

Value

Ratio from

Baseline1

Actual Value

Ratio from

Baseline1

Procalcitonin (unit)

Baseline1

n

x

x

x

Mean

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

GeoMean

x.xxx

x.xxx

x.xxx

Day 2

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

ln SD

x.xxx

x.xxx

x.xxx

GeoMean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Day 3 or 4

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

ln SD

x.xxx

x.xxx

x.xxx

GeoMean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

etc.

etc.

Note: SD: Standard Deviation

1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.

Unscheduled visits not included in post baseline assessments.



Prog

ram

min

g N

ote:

Rep

eat f

or a

ll PD

par

amet

ers

and

all s

ched

uled

pos

t bas

elin

e tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

28

of 8

2 Table 14.2.4.2 MAD: Summary of PD Parameters

Protocol: BTI-201


Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.2.

4.1

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

29

of 8

2 Table 14.2.5.1 SD: Summary of PD Parameters

Protocol: BTI-201

Per Protocol Population

Parameter

Visit

rhu-pGSN 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Actual Value

Ratio from

Baseline1

Actual

Value

Ratio from

Baseline1

Actual Value

Ratio from

Baseline1


Baseline1

n

x

x

x

Mean

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

GeoMean

x.xxx

x.xxx

x.xxx

Day 2

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

ln SD

x.xxx

x.xxx

x.xxx

GeoMean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Day 3 or 4

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

ln SD

x.xxx

x.xxx

x.xxx

GeoMean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

etc.

etc.






Prog

ram

min

g N

ote:

Rep

eat f

or a

ll PD

par

amet

ers

and

all s

ched

uled

pos

t bas

elin

e tim

epoi

nts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

30

of 8

2 Table 14.2.5.2 MAD: Summary of PD Parameters

Protocol: BTI-201

Per Protocol Population

Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.2.

5.1

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

31

of 8

2 Table 14.3.1.1 SD: Summary of Concomitant Medication

Protocol: BTI-201

Safety Population

Anatomic Therapeutic Classification (ATC3)

Preferred Term (PT)

rhu-pGSN

6 mg/kg

(N=xx)

n (%) M

Placebo

(N=xx)

n (%) M

Overall

(N=xx)

n (%) M

Subjects with at least one Concomitant Medication

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

ATC3/1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

ATC3/2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

ATC3/3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Note: If a subject has multiple occurrences of a medication, the subject is presented only once in the subject count (N).

Occurrences are counted each time in the mentions/Occurrence (M) column.

WHO-DD, XXXX



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

32

of 8

2 Table 14.3.1.2 MAD: Summary of Prior and Concomitant Medication

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

1.1

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

33

of 8

2 Table 14.3.3.1.1 SD: Overall Summary of Treatment-Emergent Adverse Events

Protocol: BTI-201

Safety Population

rhu-pGSN

6 mg/kg

(N=xx)

n (%) M

Placebo

(N=xx)

n (%) M

Overall

(N=xx)

n (%) M

Number of subjects reporting at least:

One TEAE

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

One NCI-CTEAE Grade 3 TEAE

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

One Serious TEAE

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

One Drug Related TEAE

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

TEAE Leading to Death

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

One Procedure Related TEAE

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

One TEAE leading to study treatment discontinuation

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Number of subjects reporting TEAEs by NCI-CTEAE Grade

Grade 1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 5

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Number of subjects reporting TEAEs by relationship to study medication

Definitely not Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Probably not Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Possibly Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Probably Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Definitely Related

Number of subjects reporting TEAEs by relationship to study procedure


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Possibly Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Probably Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Definitely Related

Note: A treatment-emergent adverse event (TEAE) is defined as an adverse event that occurred or worsened following

the first administration of study drug. If a subject has multiple occurrences of a TEAE, the subject is presented only once

in the Patient count (n) column for a given System Organ Class and Preferred Term. Occurrences are counted each time in the

mentions/occurrence (M) column. Related TEAE = A Possibly , Probably related TEAE or Definitely Related.MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

34

of 8

2 Table 14.3.3.1.2 MAD: Overall Summary of Treatment-Emergent Adverse Events

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

3.1.

1 In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

35

of 8

2 Table 14.3.3.2.1 SD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT)

Protocol: BTI-201

Safety Population

rhu-pGSN

6 mg/kg

(N=xx)

n (%) M

Placebo

(N=xx)

n (%) M

Overall

(N=xx)

n (%) M

Subjects with at least one TEAE

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT5

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx



in the Patient count (n) column for a given System Organ Class and Preferred Term.


MedDRA Version xx.x



Prot

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No:

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EOS

Tabl

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inal

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2 Table 14.3.3.2.2 MAD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

3.2.

1 In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

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Page

37

of 8

2 Table 14.3.3.3.1 SD: Summary of Treatment-Emergent Deaths (Summary by SOC, PT)

Protocol: BTI-201

Safety Population

rhu-pGSN

6 mg/kg

(N=xx)

n (%) M

Placebo

(N=xx)

n (%) M

Overall

(N=xx)

n (%) M

Subjects with at least one TEAE leading to Death

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT5

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx





MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

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inal

V2.

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2 Table 14.3.3.3.2 MAD: Summary of Treatment-Emergent Deaths (Summary by SOC, PT)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

3.3.

1 In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

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Page

39

of 8

2 Table 14.3.3.4.1 SD: Summary of Serious Treatment-Emergent Adverse Events (Summary by SOC, PT)

Protocol: BTI-201

Safety Population

rhu-pGSN

6 mg/kg

(N=xx)

n (%) M

Placebo

(N=xx)

n (%) M

Overall

(N=xx)

n (%) M

Subjects with at least one Serious TEAE

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT5

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx





MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

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s: M

ock

EOS

Tabl

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inal

V2.

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2018

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2 Table 14.3.3.4.2 MAD: Summary of Serious Treatment-Emergent Adverse Events (Summary by SOC, PT)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

3.4.

1 In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

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Page

41

of 8

2 Table 14.3.3.5.1 SD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and NCI-CTCAE Grade)

Protocol: BTI-201

Safety Population

rhu-pGSN

6 mg/kg

(N=xx)

n (%) M

Placebo

(N=xx)

n (%) M

Overall

(N=xx)

n (%) M


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 5

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Grade 5

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx





MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

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2018

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03

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Page

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2 Table 14.3.3.5.2 MAD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and NCI-CTCAE Grade)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

3.5.

1 In

clud

e: rh

u-pG

SN 6

mg/

kg

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

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Page

43

of 8

2 Table 14.3.1.6.1 SD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and Relationship to Study Drug)

Protocol: BTI-201

Safety Population

rhu-pGSN

6 mg/kg

(N=xx)

n (%) M

Placebo

(N=xx)

n (%) M

Overall

(N=xx)

n (%) M


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Possibly Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Probably Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Definitely Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Possibly Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Probably Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Definitely Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx





MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

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Page

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2 Table 14.3.3.6.2 MAD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and Relationship to Study Drug)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

3.6.

1 In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

45

of 8

2 Table 14.3.3.7.1 SD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and Relationship to Study Procedure)

Protocol: BTI-201

Safety Population

rhu-pGSN

6 mg/kg

(N=xx)

n (%) M

Placebo

(N=xx)

n (%) M

Overall

(N=xx)

n (%) M


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Possibly Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Probably Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Definitely Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx


xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Possibly Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Probably Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

Definitely Related

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx





MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

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Page

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of 8

2 Table 14.3.3.7.2 MAD: Summary of Treatment-Emergent Adverse Events (Summary by SOC, PT and Relationship to Study Procedure)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

3.7.

1 In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

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Page

47

of 8

2 Table 14.3.3.8.1 SD: Summary of Treatment-Emergent Adverse Events Leading to Treatment Discontinuation (Summary by SOC, PT)

Protocol: BTI-201

Safety Population

rhu-pGSN

6 mg/kg

(N=xx)

n (%) M

Placebo

(N=xx)

n (%) M

Overall

(N=xx)

n (%) M

Subjects with at least one TEAE Leading to Treatment Discontinuation

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

SOC2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT1

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT2

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT3

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT4

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT5

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx

PT6

xx (xx.x%) xx

xx (xx.x%) xx

xx (xx.x%) xx





MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

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2 Table 14.3.3.8.2 MAD: Summary of Treatment-Emergent Adverse Events Leading to Treatment Discontinuation (Summary by SOC, PT)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

3.8.

1 In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

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Page

49

of 8

2 Table 14.3.3.9.1 SD: Summary of Overall Survival

Protocol: BTI-201

Safety Population

rhu-pGSN:

6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Deaths

Number of Subjects that Died

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects that did not Die

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Survival Time (days) (95% CI1)

25th Percentile

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

Median

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

75th Percentile

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

Note: CI = Confidence Interval; 1Brookmeyer and Crowley method (1982. Log-log transformation);

Overall Survival is defined as the difference (in days) between the

time of first study drug administration to the date of death + 1 (Include the day of the study drug administration.)

Subjects who did not die will be censored at the study exit visit.



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

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Page

50

of 8

2 Table 14.3.3.9.2 MAD: Summary of Overall Survival

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

3.9.

1 In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

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Page

51

of 8

2 Table 14.3.4.1.1.1 SD: Summary of CBC (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population

Parameter

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Actual Value Change from

Baseline1


Baseline1


Baseline1

Hemoglobin (g/L)

Baseline1

n

x

x

x

Mean

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

Day 2

n

x

x

x

Mean

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

Day 3 or 4

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

etc.

etc.






Prog

ram

min

g N

ote:

In

clud

e al

l CBC

Par

amet

ers a

nd a

ll sc

hedu

led

time

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

52

of 8

2 Table 14.3.4.1.1.2 MAD: Summary of CBC (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.1.

1.1

Incl

ude

all C

BC P

aram

eter

s and

all

sche

dule

d tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

53

of 8

2 Table 14.3.4.1.2.1 SD: Summary of CBC Shifts from Baseline (Low, Normal, High)

Protocol: BTI-201

Safety Population

Parameter

Result

Classification

Baseline1

rhu-pGSN: 6 mg/kg

(N=xx)

Low

n (%)

Normal

n (%)

High

n (%)

Missing

n (%)

Total

n (%)

Hemoglobin (g/L)

Day 2

Low

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

High

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Missing

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Total

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Day 3 or 4

Low

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

High

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Missing

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Total

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

etc.

etc.

Note 1Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.




Prog

ram

min

g N

ote:

Al

so In

clud

e: P

lace

bo,

O

vera

ll In

clud

e al

l CBC

Par

amet

ers a

nd a

ll sc

hedu

led

time

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

54

of 8

2 Table 14.3.4.1.2.2 MAD: Summary of CBC Shifts from Baseline (Low, Normal, High)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.1.

2.1

Incl

ude

all C

BC P

aram

eter

s and

all

sche

dule

d tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

55

of 8

2 Table 14.3.4.2.1.1 SD: Summary of Coagulation (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population

Parameter

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)


Baseline1


Baseline1


Baseline1

PT/INR (unit)

Baseline1

n

x

x

x

Mean

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

Day 2

n

x

x

x

Mean

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

Day 3 or 4

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

etc.

etc.






Prog

ram

min

g N

ote:

In

clud

e al

l Coa

gula

tion

Para

met

ers a

nd a

ll sc

hedu

led

time

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

56

of 8

2 Table 14.3.4.2.1.2 MAD: Summary of Coagulation (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.2.

1.1

Incl

ude

all C

oagu

latio

n Pa

ram

eter

s and

all

sche

dule

d tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

57

of 8

2 Table 14.3.4.2.2.1 SD: Summary of Coagulation Shifts from Baseline (Low, Normal, High)

Protocol: BTI-201

Safety Population

Parameter

Result

Classification

Baseline1

rhu-pGSN: 6 mg/kg

(N=xx)

Low

n (%)

Normal

n (%)

High

n (%)

Missing

n (%)

Total

n (%)

PT/INR (unit)

Day 2

Low

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

High

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Missing

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Total

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Day 3 or 4

Low

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

High

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Missing

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Total

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

etc.

etc.





Prog

ram

min

g N

ote:

Al

so In

clud

e: P

lace

bo,

O

vera

ll In

clud

e al

l Coa

gula

tion

Para

met

ers a

nd a

ll sc

hedu

led

time

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

58

of 8

2 Table 14.3.4.2.2.2 MAD: Summary of Coagulation Shifts from Baseline (Low, Normal, High)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.2.

2.1

Incl

ude

all C

oagu

latio

n Pa

ram

eter

s and

all

sche

dule

d tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

59

of 8

2 Table 14.3.4.3.1.1 SD: Summary of Comprehensive Metabolic Profile (Summary of Actual and Change from Baseline Values) by

Timepoint

Protocol: BTI-201

Safety Population

Parameter

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)


Baseline1


Baseline1


Baseline1

Sodium (unit)

Baseline1

n

x

x

x

Mean

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

Day 2

n

x

x

x

Mean

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

Day 3 or 4

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

etc.

etc.






Prog

ram

min

g N

ote:

In

clud

e al

l Com

preh

ensiv

e M

etab

olic

Pro

file

Para

met

ers a

nd a

ll sc

hedu

led

time

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

60

of 8

2 Table 14.3.4.3.1.2 MAD: Summary of Comprehensive Metabolic Profile (Summary of Actual and Change from Baseline Values) by

Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.3.

1.1

Incl

ude

all C

ompr

ehen

sive

Met

abol

ic P

rofil

e Pa

ram

eter

s and

all

sche

dule

d tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

61

of 8

2 Table 14.3.4.3.2.1 SD: Summary of Comprehensive Metabolic Profile Shifts from Baseline (Low, Normal, High)

Protocol: BTI-201

Safety Population

Parameter

Result

Classification

Baseline1

rhu-pGSN: 6 mg/kg

(N=xx)

Low

n (%)

Normal

n (%)

High

n (%)

Missing

n (%)

Total

n (%)

Sodium (unit)

Day 2

Low

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

High

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Missing

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Total

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Day 3 or 4

Low

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

High

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Missing

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Total

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

etc.

etc.





Prog

ram

min

g N

ote:

Al

so In

clud

e: P

lace

bo,

O

vera

ll In

clud

e al

l Com

preh

ensiv

e M

etab

olic

Pro

file

Para

met

ers a

nd a

ll sc

hedu

led

time

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

62

of 8

2 Table 14.3.4.3.2.2 MAD: Summary of Comprehensive Metabolic Profile Shifts from Baseline (Low, Normal, High)

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.3.

2.1

Incl

ude

all C

ompr

ehen

sive

Met

abol

ic P

rofil

e Pa

ram

eter

s and

all

sche

dule

d tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

63

of 8

2 Table 14.3.4.4.1 SD: Summary of Vital Signs (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population

Parameter

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Actual Value

Change from

Baseline1

Actual

Value

Change from

Baseline1


Baseline1

Systolic blood

pressure (mmHg)

Baseline1

n

x

x

Mean

x.xxx

x.xxx

Median

x.xxx

x.xxx

SD

x.xxx

x.xxx

Minimum

x.xx

x.xx

Maximum

x.xx

x.xx

Day 1: End of

Infusion

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Day 1: 30 mins

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

etc.

etc.






Prog

ram

min

g N

ote:

In

clud

e al

l Vita

l Sig

ns P

aram

eter

s and

all

time

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

64

of 8

2 Table 14.3.4.4.2 MAD: Summary of Vital Signs (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.4.

1 In

clud

e al

l Vita

l Sig

n Pa

ram

eter

s and

all

sche

dule

d tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

65

of 8

2 Table 14.3.4.5.1 SD: Summary of Vital Signs Interpretation by Timepoint

Protocol: BTI-201

Safety Population

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Baseline1

n

xx

xx

xx

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal NCS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal CS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Day 1: 30 mins

n

xx

xx

xx

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal NCS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal CS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Day 2

n

xx

xx

xx

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal NCS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal CS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

etc.

etc.



NCS = Not Clinically Significant; CS = Clinically Significant.




Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

66

of 8

2 Table 14.3.4.5.2 MAD: Summary of Vital Signs Interpretation by Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.5.

1 In

clud

e al

l sch

edul

ed ti

me

poin

ts.

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

67

of 8

2 Table 14.3.4.6.1 SD: Summary of Mean EKG (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population

Parameter

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Actual Value

Change from

Baseline1

Actual

Value

Change from

Baseline1


Baseline1

Heart Rate (unit)

Baseline1

n

x

x

Mean

x.xxx

x.xxx

Median

x.xxx

x.xxx

SD

x.xxx

x.xxx

Minimum

x.xx

x.xx

Maximum

x.xx

x.xx

Day 28 / Early

Termination

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

PR Interval (unit) B

aseline1

n

x

x

x

Mean

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

etc.

etc.






Prog

ram

min

g N

ote:

In

clud

e al

l EKG

Par

amet

ers a

nd a

ll tim

e po

ints

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

68

of 8

2 Table 14.3.4.6.2 MAD: Summary of Mean EKG (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.6.

1 In

clud

e al

l EKG

Par

amet

ers a

nd a

ll sc

hedu

led

time

poin

ts.

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

69

of 8

2 Table 14.3.4.7.1 SD: Summary of EKG Interpretation (Worst) by Timepoint

Protocol: BTI-201

Safety Population

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Baseline1

n

xx

xx

xx

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal NCS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal CS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Day 28 / Early

Termination

n

xx

xx

xx

Normal

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal NCS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Abnormal CS

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)







Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

70

of 8

2 Table 14.3.4.7.2 MAD: Summary of EKG Interpretation (Worst) by Timepoint

Protocol: BTI-201

Safety Population



Pr

ogra

mm

ing

Not

e:

Repe

at T

able

14.

3.4.

7.1

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

71

of 8

2 Table 14.3.4.8.1 SD: Summary of CURB-65 Score(Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Actual Value

Change from

Baseline1

Actual

Value

Change from

Baseline1

Actual Value

Change from

Baseline1

Baseline1

n

x

x

Mean

x.xxx

x.xxx

Median

x.xxx

x.xxx

SD

x.xxx

x.xxx

Minimum

x.xx

x.xx

Maximum

x.xx

x.xx

Day 3 or 4

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Day 7

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

etc.






Prog

ram

min

g N

ote:

In

clud

e al

l sch

edul

ed ti

me

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

72

of 8

2 Table 14.3.4.8.2 MAD: Summary of CURB-65 Score (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.8.

1 In

clud

e al

l sch

edul

ed ti

me

poin

ts.

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

73

of 8

2 Table 14.3.4.9.1 SD: Summary of PSI Score (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Actual Value

Change from

Baseline1

Actual

Value

Change from

Baseline1

Actual Value

Change from

Baseline1

Baseline1

n

x

x

Mean

x.xxx

x.xxx

Median

x.xxx

x.xxx

SD

x.xxx

x.xxx

Minimum

x.xx

x.xx

Maximum

x.xx

x.xx

Day 3 or 4

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Day 7

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

etc.






Prog

ram

min

g N

ote:

In

clud

e al

l sch

edul

ed ti

me

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

74

of 8

2 Table 14.3.4.9.2 MAD: Summary of PSI Score (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.9.

1 In

clud

e al

l sch

edul

ed ti

me

poin

ts.

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

75

of 8

2 Table 14.3.4.10.1 SD: Summary of PSI Risk Class by Timepoint

Protocol: BTI-201

Safety Population

Visit

Risk Class

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Baseline1

n

xx

xx

xx

Class I

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Class II

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Class III

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Class IV

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Class V

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Day 28 / Early Termination

n

xx

xx

xx

Class I

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Class II

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Class III

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Class IV

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Class V

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)







Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

76

of 8

2 Table 14.3.4.10.2 MAD: Summary of PSI Risk Class by Timepoint

Protocol: BTI-201

Safety Population



Pr

ogra

mm

ing

Not

e:

Repe

at T

able

14.

3.4.

10.1

In

clud

e al

l sch

edul

ed ti

me

poin

ts.

Incl

ude:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

;

Com

bine

d Ac

tive;

Com

bine

d Pl

aceb

o;

O

vera

ll

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

77

of 8

2 Table 14.3.4.11.1 SD: Summary of SOFA Score (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Actual Value

Change from

Baseline1

Actual

Value

Change from

Baseline1

Actual Value

Change from

Baseline1

Baseline1

n

x

x

Mean

x.xxx

x.xxx

Median

x.xxx

x.xxx

SD

x.xxx

x.xxx

Minimum

x.xx

x.xx

Maximum

x.xx

x.xx

Day 3 or 4

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Day 7

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

etc.






Prog

ram

min

g N

ote:

In

clud

e al

l sch

edul

ed ti

me

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

78

of 8

2 Table 14.3.4.11.2 MAD: Summary of SOFA Score (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.11

.1

Incl

ude

all s

ched

uled

tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

79

of 8

2 Table 14.3.4.12.1 SD: Summary of MMSE Score (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population

Visit

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Actual Value

Change from

Baseline1

Actual

Value

Change from

Baseline1

Actual Value

Change from

Baseline1

Baseline1

n

x

x

Mean

x.xxx

x.xxx

Median

x.xxx

x.xxx

SD

x.xxx

x.xxx

Minimum

x.xx

x.xx

Maximum

x.xx

x.xx

Day 3 or 4

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Day 7

n

x

x

x

x

x

x

Mean

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Median

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

SD

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

x.xxx

Minimum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

Maximum

x.xx

x.xx

x.xx

x.xx

x.xx

x.xx

etc.






Prog

ram

min

g N

ote:

In

clud

e al

l sch

edul

ed ti

me

poin

ts.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

80

of 8

2 Table 14.3.4.12.2 MAD: Summary of MMSE Score (Summary of Actual and Change from Baseline Values) by Timepoint

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.12

.1

Incl

ude

all s

ched

uled

tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

81

of 8

2 Table 14.3.4.13.1 SD: Summary of Hospitalization

Protocol: BTI-201

Safety Population

Parameter (Kaplan-Meier Estimates)

rhu-pGSN: 6 mg/kg

(N=xx)

Placebo

(N=xx)

Overall

(N=xx)

Hospital Stay

Number of Subjects Discharged

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects not Discharged

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Length of Stay in Hospital (hours) (95% CI1)

25th Percentile

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

Median

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

75th Percentile

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

ICU Stay

Number of Subjects in ICU

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects not in ICU

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Length of Stay in ICU (days) (95% CI1)

25th Percentile

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

Median

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

75th Percentile

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

Intubation

Number of Subjects Intubated

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Number of Subjects not Intubated

xx (xx.x%)

xx (xx.x%)

xx (xx.x%)

Length of Intubation (days) (95% CI1)

25th Percentile

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

Median

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

75th Percentile

xx (xx.x, xx.x)

xx (xx.x, xx.x)

xx (xx.x, xx.x)

Note: CI = Confidence Interval; 1Brookmeyer and Crowley method (1982. Log-log transformation);

Length of stay in hospital is defined as the date and time of discharge/date of study exit (23:59 PM ) -

date and time of hospitalization admission due to CAP in hours



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Tabl

es, F

inal

V2.

0 Am

endm

ent V

1.0

2018

-12-

03

Nov

otec

h –

Stric

tly C

onfid

entia

l

Page

82

of 8

2 Table 14.3.4.13.2 MAD: Summary of Hospitalization

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

Re

peat

Tab

le 1

4.3.

4.13

.1

Incl

ude

all s

ched

uled

tim

e po

ints

. In

clud

e: rh

u-pG

SN 6

mg/

kg;

rh

u-pG

SN 1

2 m

g/kg

;

rhu-

pGSN

24

mg/

kg;

Co

mbi

ned

Activ

e;

Co

mbi

ned

Plac

ebo;

Ove

rall

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

of 8

3

BT

I-201

: Moc

k Li

stin

gs: T

able

of C

onte

nts

Listings

List

ing

16.2

.1.2

.1 S

D:

Subj

ect

Disp

osit

ion

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 6

List

ing

16.2

.1.2

.2 M

AD:

Sub

ject

Dis

posi

tion

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

7

List

ing

16.2

.2.1

SD:

Pr

otoc

ol D

evia

tion

s ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 7

Li

stin

g 16

.2.2

.2 M

AD: P

roto

col

Devi

atio

ns ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 9

List

ing

16.2

.3.1

SD:

An

alys

is P

opul

atio

ns ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

10

List

ing

16.2

.3.2

MAD

: A

naly

sis

Popu

lati

ons

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

11

List

ing

16.2

.4.1

.1 S

D:

Demo

grap

hics

and

Base

line

Cha

ract

eris

tics

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 12

Li

stin

g 16

.2.4

.1.2

MAD:

Dem

ogra

phic

s an

d Bas

elin

e Ch

arac

teri

stics

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

13

List

ing

16.2

.4.2

.1 S

D:

Vira

l Se

rolo

gy ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

... 1

4 Li

stin

g 16

.2.4

.2.2

MAD:

Vir

al S

erol

ogy

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 1

5 Li

stin

g 16

.2.4

.3.1

SD:

Medi

cal

Hist

ory

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 1

6 Li

stin

g 16

.2.4

.3.2

MAD:

Med

ical

His

tory

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 17

List

ing

16.2

.4.4

.1 S

D:

Preg

nanc

y Te

st R

esult

s ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 18

Li

stin

g 16

.2.4

.4.2

MAD:

Pre

gnan

cy T

est

Resul

ts ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

19

List

ing

16.2

.4.5

.1 S

D:

Conf

irma

tion

of

CAP

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

20

List

ing

16.2

.4.5

.2 M

AD:

Con

firm

atio

n of

CAP

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 2

1 Li

stin

g 16

.2.4

.6.1

SD:

Elig

ibil

ity

Asse

ssmen

t ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 22

Li

stin

g 16

.2.4

.6.2

MAD:

Eli

gibi

lity

Cri

teria

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 23

List

ing

16.2

.4.7

.1 S

D:

Prio

r Me

dica

tion

s ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 24

Li

stin

g 16

.2.4

.7.2

MAD:

Pri

or M

edic

atio

ns ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

25

List

ing

16.2

.5.1

.1 S

D:

Rand

omiz

atio

n ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

26

List

ing

16.2

.5.1

.2 M

AD:

Ran

domi

zati

on ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

... 2

7 Li

stin

g 16

.2.5

.2.1

SD:

Stud

y Dr

ug A

dmin

istra

tion

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 2

8 Li

stin

g 16

.2.5

.2.2

MAD:

Stu

dy D

rug

Admi

nistr

atio

n ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

29

List

ing

16.2

.5.3

.1 S

D:

Stud

y Dr

ug I

nter

rupti

on ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

30

List

ing

16.2

.5.3

.2 M

AD:

Stu

dy D

rug

Inte

rrupt

ion

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

31

List

ing

16.2

.6.1

.1 S

D:

Indi

vidu

al p

GSN

Plasm

a Co

ncen

trat

ions

(uni

t) ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 3

2 Li

stin

g 16

.2.6

.1.2

MAD:

Ind

ivid

ual

pGSN

Plas

ma C

once

ntra

tion

s (un

it)

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 3

3 Li

stin

g 16

.2.6

.2.1

SD:

Indi

vidu

al Est

imat

ed

Plas

ma r

hu-p

GSN

Conce

ntra

tion

s (u

nit)

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 3

4 Li

stin

g 16

.2.6

.2.2

MAD:

Ind

ivid

ual

Esti

mated

Pla

sma

rhu-pG

SN C

onc

entr

atio

ns (un

it)

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 35

List

ing

16.2

.6.3

.1 S

D:

Indi

vidu

al p

GSN

Plasm

a PK

Par

amet

ers

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 36

Li

stin

g 16

.2.6

.3.2

MAD:

Ind

ivid

ual

pGSN

Plas

ma P

K Pa

rame

ters

by D

ay ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 3

7 Li

stin

g 16

.2.6

.4.1

SD:

Indi

vidu

al Est

imat

ed

Plas

ma r

hu-p

GSN

PK Pa

rame

ters

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

38

List

ing

16.2

.6.4

.2 M

AD:

Ind

ivid

ual

Esti

mated

Pla

sma

rhu-pG

SN P

K P

aram

eter

s by

Day

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 3

9

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

of 8

3

List

ing

16.2

.6.5

.1 S

D:

Anti

-rhu

-pGS

N An

tibod

ies

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

40

List

ing

16.2

.6.5

.2 M

AD:

Ant

i-rh

u-pG

SN A

ntibo

dies

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 4

1 Li

stin

g 16

.2.6

.6.1

SD:

Biom

arke

rs ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 42

List

ing

16.2

.6.6

.2 M

AD:

Bio

marker

s ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 4

3 Li

stin

g 16

.2.6

.7.1

SD:

Sput

um a

nd B

lood

Cult

ure

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

44

List

ing

16.2

.6.7

.2 M

AD:

Spu

tum

and

Bloo

d Cul

ture

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 4

5 Li

stin

g 16

.2.7

.1.1

SD:

Adve

rse

Even

ts ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

... 4

6 Li

stin

g 16

.2.7

.1.2

MAD:

Adv

erse

Eve

nts

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 4

7 Li

stin

g 16

.2.7

.2.1

SD:

Seri

ous

Adve

rse

Event

s ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 48

Li

stin

g 16

.2.7

.2.2

MAD:

Ser

ious

Adv

erse

Even

ts ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

49

List

ing

16.2

.7.3

.1 S

D:

Adve

rse

Even

ts L

eadin

g to

Stu

dy M

edic

ation

Dis

cont

inua

tion

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 5

0 Li

stin

g 16

.2.7

.3.2

MAD:

Adv

erse

Eve

nts

Leadi

ng t

o St

udy

Medi

catio

n Di

scon

tinu

atio

n ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 5

1 Li

stin

g 16

.2.7

.4.1

SD:

Over

all

Surv

ival

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 52

List

ing

16.2

.7.4

.2 M

AD:

Ove

rall

Sur

viva

l ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 53

Li

stin

g 16

.2.8

.1.1

.1 SD

: CB

C ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

54

List

ing

16.2

.8.1

.1.2

MA

D: C

BC ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 5

5 Li

stin

g 16

.2.8

.1.2

.1 SD

: Ab

norm

al C

BC ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

... 5

6 Li

stin

g 16

.2.8

.1.2

.2 MA

D: A

bnor

mal

CBC

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 5

7 Li

stin

g 16

.2.8

.2.1

.1 SD

: Co

agul

atio

n ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

58

List

ing

16.2

.8.2

.1.2

MA

D: C

oagu

lati

on ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

... 5

9 Li

stin

g 16

.2.8

.2.2

.1 SD

: Ab

norm

al C

oagu

latio

n ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 60

Li

stin

g 16

.2.8

.2.2

.2 MA

D: A

bnor

mal

Coag

ulati

on ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

61

List

ing

16.2

.8.3

.1.1

SD

: Co

mpre

hens

ive

Metab

olic

Pro

file

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

... 6

2 Li

stin

g 16

.2.8

.3.1

.2 MA

D: C

ompr

ehen

sive

Meta

boli

c Pr

ofil

e ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 6

3 Li

stin

g 16

.2.8

.3.2

.1 SD

: Ab

norm

al C

ompr

ehens

ive

Meta

boli

c Pr

ofile

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

64

List

ing

16.2

.8.3

.2.2

MA

D: A

bnor

mal

Comp

rehen

sive

Met

abol

ic P

rofil

e ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

65

List

ing

16.2

.9.1

SD:

Vi

tal

Sign

s ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

... 6

6 Li

stin

g 16

.2.9

.2 M

AD: V

ital

Sig

ns ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 67

List

ing

16.2

.10.

1 SD

: E

KG ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 68

Li

stin

g 16

.2.1

0.2

MAD:

EKG

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 69

Li

stin

g 16

.2.1

1.1

SD: P

hysi

cal

Exam

inat

ion

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

70

List

ing

16.2

.11.

2 MA

D:

Phys

ical

Exa

mina

tion

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 7

1 Li

stin

g 16

.2.1

2.1.

1 SD:

Out

come

Pre

dict

ion M

odel

s CU

RB-6

5 ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 7

2 Li

stin

g 16

.2.1

2.1.

2 MAD

: Ou

tcom

e Pr

edic

tion

Mode

ls C

URB-65

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 7

3 Li

stin

g 16

.2.1

2.2.

1 SD:

Out

come

Pre

dict

ion M

odel

s PS

I (P

ort

Score

) ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

74

List

ing

16.2

.12.

2.2

MAD

: Ou

tcom

e Pr

edic

tion

Mode

ls P

SI (

Port

Scor

e) ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 7

5 Li

stin

g 16

.2.1

2.3.

1 SD:

Out

come

Pre

dict

ion M

odel

s SO

FA S

core

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

76

List

ing

16.2

.12.

3.2

MAD

: Outc

ome

Pred

icti

on

Mode

ls S

OFA

Scor

e ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

77

List

ing

16.2

.12.

4.1

SD:

Out

come

Pre

dict

ion M

odel

s MM

SE S

core

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

78

List

ing

16.2

.12.

4.2

MAD

: Ou

tcom

e Pr

edic

tion

Mode

ls M

MSE

Scor

e ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

79

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

of 8

3

List

ing

16.2

.13.

1 SD

: C

onco

mita

nt M

edic

ation

s ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 80

Li

stin

g 16

.2.1

3.2

MAD:

Conc

omit

ant

Medi

catio

n ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 81

Li

stin

g 16

.2.1

4.1

SD: H

ospi

tali

zati

on F

ollow

-Up

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

82

List

ing

16.2

.14.

2 MA

D:

Hosp

ital

izat

ion

Follo

w-Up

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 8

3

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

of 8

3

GEN

ERAL

CO

MM

ENTS

Unl

ess o

ther

wise

stat

es, p

aram

eter

s will

be

liste

d in

alp

habe

tical

ord

er

Ch

ange

from

Bas

elin

e:

Chan

ge fr

om B

asel

ine

will

be

calc

ulat

ed a

s:

N

ames

and

ord

er o

f Tre

atm

ent G

roup

s SD

:

Coho

rt 1

: rhu

-pGS

N 6

mg/

kg;

Co

hort

1: P

lace

bo

MAD

: Co

hort

2: r

hu-p

GSN

6 m

g/kg

;

Coho

rt 2

: Pla

cebo

Coho

rt 3

: rhu

-pGS

N 1

2 m

g/kg

;

Coho

rt 3

: Pla

cebo

Coho

rt 4

: rhu

-pGS

N 2

4 m

g/kg

;

Coho

rt 4

: Pla

cebo

Nam

es o

f visi

ts

SD:

Sc

reen

ing

Da

y 1

Da

y 2

Da

y 3/

4

Day

7

Day

14

Da

y 28

/ Ea

rly T

erm

inat

ion

(Com

bine

d vi

sit fo

r saf

ety

and

effic

acy)

Uns

ched

uled

MAD

: Sc

reen

ing

Da

y 1

Da

y 2

Da

y 3

Da

y 4

Da

y 7

Da

y 14

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

of 8

3

Da

y 28

/ Ea

rly T

erm

inat

ion

(Com

bine

d vi

sit fo

r saf

ety

and

effic

acy)

Uns

ched

uled

Colu

mn

wid

ths a

nd te

xt-w

rapp

ing

may

be

alte

red

in fi

nal o

utpu

t in

orde

r to

best

pre

sent

the

data

Foot

note

s may

be

adde

d/am

ende

d if

requ

ired

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

of 8

3

Listing 16.2.1.2.1 SD: Subject Disposition

Protocol: BTI-201


Cohort 1: rhu-pGSN 6 mg/kg

Subject

Final Disposition

Reason for Discontinuation

Date of Study Exit

(DDMMMYYYY)

Date of Last Contact

(DDMMMYYYY)

XXX

Withdrawn

Due to Adverse Event:

AE#: XXXXXXXXXXXX

DDMMMYYYY

DDMMMYYYY

XXX

Completed

DDMMMYYYY

XXX

Completed

DDMMMYYYY

XXX

Withdrawn

Other: XXXXXXXXXXXXX

DDMMMYYYY

etc.



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

of 8

3

Listing 16.2.1.2.2 MAD: Subject Disposition

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.1.2

.1 fo

r MAD

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 8

of 8

3

Listing 16.2.2.1 SD: Protocol Deviations

Protocol: BTI-201



Subject

Type of Deviation

Date of Deviation

(DDMMMYYYY)

Description of Deviation

XXX

ABCD

DDMMMYYYY

ABCD

ABCD

DDMMMYYYY

ABCD

…

XXX

ABCD

DDMMMYYYY

ABCD

ABCD

DDMMMYYYY

ABCD

…

XXX

ABCD

DDMMMYYYY

ABCD

ABCD

DDMMMYYYY

ABCD

…

XXX

ABCD

DDMMMYYYY

ABCD

XXX

ABCD

DDMMMYYYY

ABCD


Page x of x


Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 9

of 8

3

Listing 16.2.2.2 MAD: Protocol Deviations

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

. 2.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

0 of

83

Listing 16.2.3.1 SD: Analysis Populations

Protocol: BTI-201



Subject

Intent-to-Treat

Population

Safety

Population

PK

Population

Per Protocol

Population

XXX

Yes

Yes

Yes

Yes

XXX

Yes

Yes

Yes

Yes

XXX

Yes

Yes

Yes

Yes

XXX

Yes

Yes

Yes

Yes

XXX

Yes

Yes

Yes

Yes

XXX

Yes

Yes

Yes

Yes

XXX

Yes

Yes

Yes

Yes

Etc.



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

1 of

83

Listing 16.2.3.2 MAD: Analysis Populations

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.3.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

2 of

83

Listing 16.2.4.1.1 SD: Demographics and Baseline Characteristics

Protocol: BTI-201



Subject

Date of

Informed

Consent

(DDMMMYYYY)

Protocol

Version

Date of

Birth

(DDMMMYYYY)

Age at

Informed

Consent

Sex

Child

Bearing

Potential

Contraceptive

Methods

Race

Height

(cm)

Weight

(kg)

XXX

DDMMMYYYY

Amendment 1 DDMMMYYYY

xx

Male

White

xxx

xx.x

XXX

DDMMMYYYY


xx

Female

No

White

xxx

xx.x

XXX

DDMMMYYYY


xx

Male

White

xxx

xx.x

XXX

DDMMMYYYY


xx

Female

Yes

Hormonal

methods

Other:

XXXXXXXXX

xxx

xx.x

etc.



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

3 of

83

Listing 16.2.4.1.2 MAD: Demographics and Baseline Characteristics

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.4.1

.1 fo

r MAD

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

4 of

83

Listing 16.2.4.2.1 SD: Viral Serology

Protocol: BTI-201



Subject

Visit

Visit Date

(DDMMMYYYY

Test

Result

Most Recent

Viral Load

(unit)

Most Recent

CD4 Count

(unit)

XXX

Screening

DDMMMYYYY

HIV

Negative

xxxxxx

xxx.x

Hepatitis B

Surface Antigen

Negative

Hepatitis C

Negative

XXX

Screening

DDMMMYYYY

HIV

Negative

xxxxxx

xxx.x

Hepatitis B

Surface Antigen

Negative

Hepatitis C

Negative

etc.



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

5 of

83

Listing 16.2.4.2.2 MAD: Viral Serology

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.4.2

.1 fo

r MAD

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

6 of

83

Listing 16.2.4.3.1 SD: Medical History

Protocol: BTI-201



Subject

Condition/

Body System

System Organ Class /

Preferred Term

Date of

Diagnosis

(DDMMMYYYY)

Resolution Date

(DDMMMYYYY)

Concomitant

Medication

Taken

Ongoing

XXX

XXXXXXXXXXXX/

YYYYYYYYYYYY

XXXXXXXXXX/ YYYYYYYYY/

ZZZZZZZZZ

DDMMMYYYY

DDMMMYYYY

No

No

XXXXXXXXXXXX/

YYYYYYYYYYYY


ZZZZZZZZZ

DDMMMYYYY

DDMMMYYYY

Yes

Yes

…

XXX

XXXXXXXXXXXX/

YYYYYYYYYYYY


ZZZZZZZZZ

DDMMMYYYY

DDMMMYYYY

No

No

XXX

XXXXXXXXXXXX/

YYYYYYYYYYYY


ZZZZZZZZZ

DDMMMYYYY

DDMMMYYYY

…

XXX

XXXXXXXXXXXX/

YYYYYYYYYYYY


ZZZZZZZZZ

DDMMMYYYY

DDMMMYYYY

No

No

XXX

XXXXXXXXXXXX/

YYYYYYYYYYYY


ZZZZZZZZZ

DDMMMYYYY

DDMMMYYYY

No

No

Note: MedDRA Version XX.X



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

7 of

83

Listing 16.2.4.3.2 MAD: Medical History

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.4.3

.1 fo

r MAD

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

8 of

83

Listing 16.2.4.4.1 SD: Pregnancy Test Results

Protocol: BTI-201



Subject

Assessment Performed –

Reason Not Performed

Visit

Sample Date/ Time

(DDMMMYYY/ HH:MM)

Sample Type

Result

XXX

Yes

Screening

DDMMMYYY/ HH:MM

Serum

Negative

Day 1

DDMMMYYY/ HH:MM

Urine

Negative

Day 28 / Early

Termination

DDMMMYYY/ HH:MM

Urine

Negative

XXX

Yes

Screening

DDMMMYYY/ HH:MM

Serum

Negative

Day 1

DDMMMYYY/ HH:MM

Urine

Negative

Day 28 / Early

Termination

DDMMMYYY/ HH:MM

Urine

Negative

XXX

Yes

Screening

DDMMMYYY/ HH:MM

Serum

Negative

Day 1

DDMMMYYY/ HH:MM

Urine

Negative

Day 28 / Early

Termination

DDMMMYYY/ HH:MM

Urine

Negative

etc.



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

9 of

83

Listing 16.2.4.4.2 MAD: Pregnancy Test Results

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.4.4

.1 fo

r MAD

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

0 of

83

Listing 16.2.4.5.1 SD: Confirmation of CAP

Protocol: BTI-201



Subject

Visit

Visit Date

(DDMMMYYY)

Was there

clinical

confirmation

of CAP

Was there

radiological

confirmation

of CAP (CXR

or CT)

Was CXR or

CT Scan

Performed:

Date

Performed

(DDMMMYYY)

CXR or CT

Scan

Findings

Date and Time of

presentation to

the hospital

(DDMMMYYY/

HH:MM)

Date and Time of

Hospitalization

Admission due to

CAP

(DDMMMYYY/

HH:MM)

Subject

Randomized

XXX

Screening

DDMMMYYYY

Yes

Yes

Yes:

DDMMMYYYY

XXXXXXXXX

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

XXX

Screening

DDMMMYYYY

Yes

Yes

Yes:

DDMMMYYYY

XXXXXXXXX

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

XXX

Screening

DDMMMYYYY

Yes

Yes

Yes:

DDMMMYYYY

XXXXXXXXX

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

etc.



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

1 of

83

Listing 16.2.4.5.2 MAD: Confirmation of CAP

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.4.5

.2 fo

r MAD

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

2 of

83

Listing 16.2.4.6.1 SD: Eligibility Assessment

Protocol: BTI-201



Subject

Eligibility Assessment

Date

(DDMMMYYYY)

Did the patient meet all

inclusion criteria?

Inclusion

criterion

not met

Did the patient meet all

exclusion criteria?

Exclusion

Criterion

not met

XXX

DDMMMYYYY

Yes

Yes

XXX

DDMMMYYYY

Yes

Yes

XXX

DDMMMYYYY

Yes

Yes

XXX

DDMMMYYYY

Yes

Yes

XXX

DDMMMYYYY

Yes

Yes

XXX

DDMMMYYYY

Yes

Yes



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

3 of

83

Listing 16.2.4.6.2 MAD: Eligibility Criteria

Protocol: BTI-201



Pr

ogra

mm

ing

Not

e:

Repe

at L

istin

g 16

.2.4

.6.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

4 of

83

Listing 16.2.4.7.1 SD: Prior Medications

Protocol: BTI-201



Subject

Number

CM#

Drug Name/ATC3/PT

Indication

Start Date/

Stop Date

(DDMMMYYYY)

Ongoing

Dose

Unit

Frequency

Route

XXX

1

XXXXXXXXXXXXXXXXXXXXXX/

ZZZZZZZZZZZZZZZZZZZZZZ/

YYYYYYYYYYYYYYYYYYYYYY

Pre-existing

condition: MH#

DDMMMYYYY /

DDMMMYYYY

No

XX

Unit

YYYYYY

ZZZZZ

2




Other: YYYYYY

DDMMMYYYY /

DDMMMYYYY

No

XX

Unit

YYYYYY

ZZZZZ

XXX

1




Other: YYYYYY

DDMMMYYYY /

DDMMMYYYY

No

XX

Unit

YYYYYY

ZZZZZ

2




Other: YYYYYY

DDMMMYYYY /

DDMMMYYYY

No

XX

Unit

YYYYYY

ZZZZZ

XXX

1




Pre-existing

condition: MH#

DDMMMYYYY /

DDMMMYYYY

No

XX

Unit

YYYYYY

ZZZZZ

Etc.

Note: Prior medications are defined as any medication where the use was stopped prior to the first administration of the study

medication.

WHO-DD, xxxxxxxxxx



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

5 of

83

Listing 16.2.4.7.2 MAD: Prior Medications

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.4.7

.1 fo

r MAD

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

6 of

83

Listing 16.2.5.1.1 SD: Randomization

Protocol: BTI-201



Subject

Date /Time of

Randomization

(DDMMMYYYY/ HH:MM)

Randomization Number

Date /Time of

Emergency Unblinding

(DDMMMYYYY/ HH:MM)

Reason for Emergency Unblinding

XXX

DDMMMYYYY/ HH:MM

XXXXX

XXX

DDMMMYYYY/ HH:MM

XXXXX

XXX

DDMMMYYYY/ HH:MM

XXXXX

XXX

DDMMMYYYY/ HH:MM

XXXXX

DDMMMYYYY/ HH:MM

XXXXXXXXXXXXXXXXXXXXXXXXXXX

XXX

DDMMMYYYY/ HH:MM

XXXXX

XXX

DDMMMYYYY/ HH:MM

XXXXX

etc.



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

7 of

83

Listing 16.2.5.1.2 MAD: Randomization

Protocol: BTI-201



Pr

ogra

mm

ing

Not

e:

Repe

at L

istin

g 16

.2.5

.1.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

8 of

83

Listing 16.2.5.2.1 SD: Study Drug Administration

Protocol: BTI-201



Subject

Visit

Was Study Drug

Administered? (If

no, provide

reason)

Start Date/ Time

of Injection

(DDMMMYYYY/ HH:MM)

Stop Date/ Time

of Injection

(DDMMMYYYY/

HH:MM)

Study Drug

Administered

per Dose

Prescribed

Reason not

Successfully

Administered

Volume

Administered

(mL)

Total Duration

of Injection

(Including

Interruptions

- minutes)

XXX

Day 1

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

xx

xx

XXX

Day 1

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

xx

xx

XXX

Day 1

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

No

XXXXXXXXXXXX

xx

XXX

Day 1

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

xx

xx

XXX

Day 1

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

xx

xx

XXX

Day 1

No - XXXXXXXXX



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

9 of

83

Listing 16.2.5.2.2 MAD: Study Drug Administration

Protocol: BTI-201



Subject

Visit

Was Study Drug

Administered? (If

no, provide

reason)

Start Date/ Time of

Injection

(DDMMMYYYY/ HH:MM)

Stop Date/ Time

of Injection

(DDMMMYYYY/

HH:MM)

Study Drug

Administered

per Dose

Prescribed

Reason not

Successfully

Administered

Volume

Administered

(mL)

Total Duration

of Injection

(Including

Interruptions

- minutes)

XXX

Day 1

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

xx

xx

Day 2

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

xx

xx

Day 3

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

No

XXXXXXXXXXXX

xx

xx

XXX

Day 1

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

xx

xx

Day 2

Yes

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

Yes

xx

xx

Day 3

No - XXXXXXXXX



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

0 of

83

Listing 16.2.5.3.1 SD: Study Drug Interruption

Protocol: BTI-201



Subject

Visit

Interruption

Date and Time of

Interruption

(DDMMMYYYY/ HH:MM)

Date and Time of

Injection Re-start

(DDMMMYYYY/ HH:MM)

Reason for Interruption

XXX

Day 1

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

XXX

Day 1

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM


2

XXX

Day 1

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM


XXX

Day 1

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM


XXX

Day 1

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM




Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

1 of

83

Listing 16.2.5.3.2 MAD: Study Drug Interruption

Protocol: BTI-201



Subject

Visit

Interruption

Date and Time of

Interruption

(DDMMMYYYY/ HH:MM)

Date and Time of

Injection Re-start

(DDMMMYYYY/ HH:MM)

Reason for Interruption

XXX

Day 1

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM


XXX

Day 2

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM


XXX

Day 1

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM


XXX

Day 3

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM


XXX

Day 1

1

DDMMMYYYY/ HH:MM

DDMMMYYYY/ HH:MM




Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

2 of

83

Listing 16.2.6.1.1 SD: Individual pGSN Plasma Concentrations (unit)

Protocol: BTI-201



Subject

Number

Day

Date/Time

of Dose on

Dosing Day

(DDMMMYYYY/

HH:MM)

Sampling Time

Was PK

Sample

Collected?

Date of

PK Sample

Collection

(DDMMMYYYY)

Time of

PK Sample

Collection

(HH:MM)

Time

Deviation

Concen-

tration

(ng/mL)

Ratio

from Pre-

Injection

Day 1

Ratio

from Pre-

Injection

/ Placebo

Ratio

from Pre-

Injection

Comments

XXX

1

DDMMMYYYY/

HH:MM

Pre-Injection

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

YYYYYYYY

5 to 10 mins

post

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

X.XX

X.XX

2 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

8 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

12 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

16 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

24 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

XXX

1

DDMMMYYYY/

HH:MM

Pre-Injection

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

5 to 10 mins

post

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

X.XX

X.XX

YYYYYYYY

2 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

8 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

12 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

….

16 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

24 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

3 of

83

Listing 16.2.6.1.2 MAD: Individual pGSN Plasma Concentrations (unit)

Protocol: BTI-201



Subject

Number

Day

Date/Time

of Dose on

Dosing Day

(DDMMMYYYY/

HH:MM)

Sampling Time

Was PK

Sample

Collected?

Date of

PK Sample

Collection

(DDMMMYYYY)

Time of

PK Sample

Collection

(HH:MM)

Time

Deviation

Concen-

tration

(ng/mL)

Ratio

from Pre-

Injection

Day 1

Ratio

from Pre-

Injection

/ Placebo

Ratio

from Pre-

Injection

Comments

XXX

1

DDMMMYYYY/

HH:MM

Pre-Injection

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

YYYYYYYY

5 to 10 mins

post

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

X.XX

X.XX

2 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

8 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

12 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

16 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

24 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

2

DDMMMYYYY/

HH:MM

Pre-Injection

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

5 to 10 mins

post

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

X.XX

X.XX

YYYYYYYY

2 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

8 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

12 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

….

16 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

24 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

4 of

83

Listing 16.2.6.2.1 SD: Individual Estimated Plasma rhu-pGSN Concentrations (unit)

Protocol: BTI-201



Subject

Number

Day

Date/Time

of Dose on

Dosing Day

(DDMMMYYYY/

HH:MM)

Sampling Time

Was PK

Sample

Collected?

Date of

PK Sample

Collection

(DDMMMYYYY)

Time of

PK Sample

Collection

(HH:MM)

Time

Deviation

Concen-

tration

(ng/mL)

Change

from Pre-

Injection

Day 1

(Change

from Pre-

Injection)

– (Mean

Placebo

Change from

Pre-

Injection)

Comments

XXX

1

DDMMMYYYY/

HH:MM

Pre-Injection

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

YYYYYYYY

5 to 10 mins

post

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

X.XX

X.XX

2 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

8 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

12 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

16 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

24 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

XXX

1

DDMMMYYYY/

HH:MM

Pre-Injection

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

5 to 10 mins

post

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

X.XX

X.XX

YYYYYYYY

2 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

8 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

12 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

….

16 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

24 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

5 of

83

Listing 16.2.6.2.2 MAD: Individual Estimated Plasma rhu-pGSN Concentrations (unit)

Protocol: BTI-201



Subject

Number

Day

Date/Time

of Dose on

Dosing Day

(DDMMMYYYY/

HH:MM)

Sampling Time

Was PK

Sample

Collected?

Date of

PK Sample

Collection

(DDMMMYYYY)

Time of

PK Sample

Collection

(HH:MM)

Time

Deviation

Concen-

tration

(ng/mL)

Change

from Pre-

Injection

Day 1

(Change

from Pre-

Injection)

– (Mean

Placebo

Change from

Pre-

Injection)

Comments

XXX

1

DDMMMYYYY/

HH:MM

Pre-Injection

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

YYYYYYYY

5 to 10 mins

post

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

X.XX

X.XX

2 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

8 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

12 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

16 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

24 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

2

DDMMMYYYY/

HH:MM

Pre-Injection

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

5 to 10 mins

post

Yes

DDMMMYYYY

HH:MM

xx mins

XXX

X.XX

X.XX

YYYYYYYY

2 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

8 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

12 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

….

16 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX

24 hours post

Yes

DDMMMYYYY

HH:MM

xx hours

XXX

X.XX

X.XX



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

6 of

83

Listing 16.2.6.3.1 SD: Individual pGSN Plasma PK Parameters

Protocol: BTI-201



Day 1

Subject

Number

AUC0-t

(unit)

AUC0-8h

(unit)

AUC0-inf

(unit)

Cmax

(unit)

Tmax

(unit)

kel

(unit)

t½

(unit)

CL/F

(unit)

Vz/F

(unit) %AUCext DN_AUC0-t DN_AUC0-8 DN_AUC0-inf

DN_Cmax

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

….



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

7 of

83

Listing 16.2.6.3.2 MAD: Individual pGSN Plasma PK Parameters by Day

Protocol: BTI-201



Day 1

Subject

Number

AUC0-t

(unit)

AUC0-8h

(unit)

AUC0-inf

(unit)

Cmax

(unit)

Tmax

(unit)

kel

(unit)

t½

(unit)

CL/F

(unit)

Vz/F

(unit) %AUCext DN_AUC0-t DN_AUC0-8 DN_AUC0-inf

DN_Cmax

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

….



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

8 of

83

Listing 16.2.6.4.1 SD: Individual Estimated Plasma rhu-pGSN PK Parameters

Protocol: BTI-201



Day 1

Subject

Number

Change from Pre-Injection

Double Delta Analysis

AUC0-t

(unit)

AUC0-8h

(unit)

Cmax

(unit)

DN_AUC0-t

DN_AUC0-8

DN_Cmax

AUC0-t

(unit)

AUC0-8h

(unit)

Cmax (unit) DN_AUC0-t

DN_AUC0-8

DN_Cmax

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

….



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

9 of

83

Listing 16.2.6.4.2 MAD: Individual Estimated Plasma rhu-pGSN PK Parameters by Day

Protocol: BTI-201



Day 1

Subject

Number

Change from Pre-Injection

Double Delta Analysis

AUC0-t

(unit)

AUC0-8h

(unit)

Cmax

(unit)

DN_AUC0-t

DN_AUC0-8

DN_Cmax

AUC0-t

(unit)

AUC0-8h

(unit)

Cmax (unit) DN_AUC0-t

DN_AUC0-8

DN_Cmax

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

XXX

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

xx.x

….



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

0 of

83

Listing 16.2.6.5.1 SD: Anti-rhu-pGSN Antibodies

Protocol: BTI-201



Prog

ram

min

g N

ote:

Li

stin

g sh

ell w

ill b

e up

date

d on

ce d

ata

tran

sfer

agr

eem

ent i

s av

aila

ble.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

1 of

83

Listing 16.2.6.5.2 MAD: Anti-rhu-pGSN Antibodies

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing 16.2.6.5.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

2 of

83

Listing 16.2.6.6.1 SD: Biomarkers

Protocol: BTI-201



Subject

Parameter (Unit)

Study Visit

Sample Date/ Time

(DDMMMYYYY/

HH:MM)

Actual

Value

Change from

Baseline

Reference

Ranges

High/ Low

Flag

Comments

XXX


Day 1*

DDMMMYYYY/ HH:MM

xx

xx, xx

Day 2

DDMMMYYYY/ HH:MM

xx

xx, xx

Day 3

DDMMMYYYY/ HH:MM

xx

xx

xx, xx

H

Day 4

DDMMMYYYY/ HH:MM

xx

xx

xx, xx

L

Etc.

Etc.

Note: *Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.

L = Below Normal Range, H = Above Normal Range



Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

3 of

83

Listing 16.2.6.6.2 MAD: Biomarkers

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing 16.2.6.6.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

4 of

83

Listing 16.2.6.7.1 SD: Sputum and Blood Culture

Protocol: BTI-201



Subject

Study Visit

Sputum Culture

Collected – Reason

Not Performed

Date/Time of

Collection

Results

Gram-Stains

Antigen

Detection

Immunoassay

Genomic

Diagnostic Test

Result

XXXXX

Screening

Yes

DDMMMYYYY/

HH:MM

XXXXX

Screening

Yes

DDMMMYYYY/

etc.



Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

5 of

83

Listing 16.2.6.7.2 MAD: Sputum and Blood Culture

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing 16.2.6.7.1

for S

D.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

6 of

83

Listing 16.2.7.1.1 SD: Adverse Events

Protocol: BTI-201



Subject

Number

AE#

Adverse Event Verbatim/

System Organ Class/

Preferred Term

Start Date/

Stop Date/

(DDMMMYYYY/

DDMMMYYYY)

SAE

Severity

(NCI-

CTCAE)

Relationship

to Study Drug

Relationship

to Study

Procedure

Action

Taken

with

Study

Drug

Other

Action

Outcome

TEAE

XXX

1




DDMMMYYYY/

HH:MM

DDMMMYYYY/

HH:MM

Yes

Grade 1

Possibly

Related

Possibly

Related

None

None Recovered /

Resolved

Yes

2




DDMMMYYYY/

HH:MM

DDMMMYYYY/

HH:MM

Yes

Grade 1

Definitely

not Related

Definitely

not Related

None

None Recovered /

Resolved

Yes

XXX

1




DDMMMYYYY/

HH:MM

DDMMMYYYY/

HH:MM

No

Grade 1

Definitely

not Related

Definitely

not Related

None

None Recovered /

Resolved

No

2




DDMMMYYYY /

Ongoing

No

Grade 1

Definitely

not Related

Definitely

not Related

Drug

withdrawn None Recovered /

Resolved

Yes

etc.

Note: TEAE = A treatment-emergent adverse event.

MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

7 of

83

Listing 16.2.7.1.2 MAD: Adverse Events

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing 16.2.7.1.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

8 of

83

Listing 16.2.7.2.1 SD: Serious Adverse Events

Protocol: BTI-201



Subjec

t

Number AE#


System Organ Class/

Preferred Term

Start Date/

Stop Date/

(DDMMMYYYY/

DDMMMYYYY)

SAE

Criteria

Severity

(NCI-

CTCAE)

Relationship

to Study

Drug

Relationship

to Study

Procedure

Action

Taken

with

Study

Drug

Other

Action

Outcome

TEAE

XXX

1

XXXXXXXXXXXXXXXXXXX/

ZZZZZZZZZZZZZZZZZZZ/

YYYYYYYYYYYYYYYYYYY

DDMMMYYYY/

HH:MM

DDMMMYYYY/

HH:MM

Is Life

Threatening Grade 1

Possibly

Related

Possibly

Related

None

None Recovered /

Resolved

Yes

2



YYYYYYYYYYYYYYYYYYY

DDMMMYYYY/

HH:MM

DDMMMYYYY/

HH:MM

Is Life

Threatening Grade 1

Definitely

not Related

Definitely

not Related

None

None Recovered /

Resolved

Yes

XXX

1



YYYYYYYYYYYYYYYYYYY

DDMMMYYYY/

HH:MM

DDMMMYYYY/

HH:MM

Is Life

Threatening Grade 1

Definitely

not Related

Definitely

not Related

None

None Recovered /

Resolved

No

2



YYYYYYYYYYYYYYYYYYY

DDMMMYYYY /

Ongoing

Is Life

Threatening Grade 1

Definitely

not Related

Definitely

not Related

Drug


Resolved

Yes

etc.


MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

9 of

83

Listing 16.2.7.2.2 MAD: Serious Adverse Events

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing 16.2.7.2.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

0 of

83

Listing 16.2.7.3.1 SD: Adverse Events Leading to Study Medication Discontinuation

Protocol: BTI-201



Subject

Number

AE#


System Organ Class/

Preferred Term

Start Date/

Stop Date/

(DDMMMYYYY/

DDMMMYYYY)

SAE

Severity

(NCI-

CTCAE)

Relationship

to Study Drug

Relationship

to Study

Procedure

Action

Taken

with

Study

Drug

Other

Action

Outcome

TEAE

XXX

1




DDMMMYYYY/

HH:MM

DDMMMYYYY/

HH:MM

Yes

Grade 1

Possibly

Related

Possibly

Related

Drug

withdrawn

None Recovered /

Resolved

Yes

2




DDMMMYYYY/

HH:MM

DDMMMYYYY/

HH:MM

Yes

Grade 1

Definitely

not Related

Definitely

not Related

Drug

withdrawn

None Recovered /

Resolved

Yes

Drug

withdrawn

XXX

1




DDMMMYYYY/

HH:MM

DDMMMYYYY/

HH:MM

No

Grade 1

Definitely

not Related

Definitely

not Related

Drug

withdrawn

None Recovered /

Resolved

No

2




DDMMMYYYY /

Ongoing

No

Grade 1

Definitely

not Related

Definitely

not Related

Drug


Resolved

Yes

etc.


MedDRA Version xx.x



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

1 of

83

Listing 16.2.7.3.2 MAD: Adverse Events Leading to Study Medication Discontinuation

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing 16.2.7.3.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

2 of

83

Listing 16.2.7.4.1 SD: Overall Survival

Protocol: BTI-201



Subject

Date of First Study Drug

Administration

(DDMMMYYYY)

Event/Censoring

Date

DDMMMYYYY)

Event or Censoring

Description

Days to Event

XXX

DDMMMYYYY

DDMMMYYYY

Death

xxx

XXX

DDMMMYYYY

DDMMMYYYY

Last assessment date

xxx

XXX

DDMMMYYYY

DDMMMYYYY

Last assessment date

xxx

XXX

DDMMMYYYY

DDMMMYYYY

Death

xxx

etc.

Note: Overall Survival is defined as the difference (in days) between the





Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

3 of

83

Listing 16.2.7.4.2 MAD: Overall Survival

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing 16.2.7.4.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

4 of

83

Listing 16.2.8.1.1.1 SD: CBC

Protocol: BTI-201



Subject

Parameter (Unit)

Study Visit

Sample Date/

Time

(DDMMMYYYY/

HH:MM)

Actual

Value

Change from

Baseline1

Reference

Ranges

High/ Low

Flag

Clinical

Significance

Abnormality

Description

XXX

Haemoglobin (unit)

Screening

DDMMMYYYY/

HH:MM

xx

xx, xx

Day 11

DDMMMYYYY/

HH:MM

xx

xx, xx

Day 2

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

H

NCS

Day 3 or 4

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

L

CS

XXXXXXXXXXXXXXX

Etc.

Etc.

Note: 1Baseline. Baseline is defined as the last valid, non-missing assessment prior to first study drug administration.

L = Below Normal Range, H = Above Normal Range, NCS = Not Clinically Significant, CS = Clinically Significant.



Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

5 of

83

Listing 16.2.8.1.1.2 MAD: CBC

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.8.1

.1.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

6 of

83

Listing 16.2.8.1.2.1 SD: Abnormal CBC

Protocol: BTI-201



Subject

Parameter (Unit)

Study Visit

Sample Date/

Time

(DDMMMYYYY/

HH:MM)

Actual

Value

Change from

Baseline1

Reference

Ranges

High/ Low

Flag

Clinical

Significance

Abnormality

Description

XXX

Haemoglobin (unit)

Day 2

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

H

NCS

Day 3 or 4

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

L

CS

XXXXXXXXXXXXXXX

Etc.

Etc.





Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

7 of

83

Listing 16.2.8.1.2.2 MAD: Abnormal CBC

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.8.1

.2.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

8 of

83

Listing 16.2.8.2.1.1 SD: Coagulation

Protocol: BTI-201



Subject

Parameter (Unit)

Study Visit

Sample Date/

Time

(DDMMMYYYY/

HH:MM)

Actual

Value

Change from

Baseline1

Reference

Ranges

High/ Low

Flag

Clinical

Significance

Abnormality

Description

XXX

PT/INR (unit)

Screening

DDMMMYYYY/

HH:MM

xx

xx, xx

Day 11

DDMMMYYYY/

HH:MM

xx

xx, xx

Day 2

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

H

NCS

Day 3 or 4

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

L

CS

XXXXXXXXXXXXXXX

Etc.

Etc.





Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

9 of

83

Listing 16.2.8.2.1.2 MAD: Coagulation

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.8.2

.1.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

0 of

83

Listing 16.2.8.2.2.1 SD: Abnormal Coagulation

Protocol: BTI-201



Subject

Parameter (Unit)

Study Visit

Sample Date/

Time

(DDMMMYYYY/

HH:MM)

Actual

Value

Change from

Baseline1

Reference

Ranges

High/ Low

Flag

Clinical

Significance

Abnormality

Description

XXX

PT/INR (unit)

Day 2

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

H

NCS

Day 3 or 4

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

L

CS

XXXXXXXXXXXXXXX

Etc.

Etc.





Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

1 of

83

Listing 16.2.8.2.2.2 MAD: Abnormal Coagulation

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.8.2

.2.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

2 of

83

Listing 16.2.8.3.1.1 SD: Comprehensive Metabolic Profile

Protocol: BTI-201



Subject

Parameter (Unit)

Study Visit

Sample Date/

Time

(DDMMMYYYY/

HH:MM)

Actual

Value

Change from

Baseline1

Reference

Ranges

High/ Low

Flag

Clinical

Significance

Abnormality

Description

XXX

Sodium (unit)

Screening

DDMMMYYYY/

HH:MM

xx

xx, xx

Day 11

DDMMMYYYY/

HH:MM

xx

xx, xx

Day 2

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

H

NCS

Day 3 or 4

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

L

CS

XXXXXXXXXXXXXXX

Etc.

Etc.


L = Below Normal Range, H = Above Normal Range, NCS = Not Clinically Significant; CS = Clinically Significant.



Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

3 of

83

Listing 16.2.8.3.1.2 MAD: Comprehensive Metabolic Profile

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.8.3

.1.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

4 of

83

Listing 16.2.8.3.2.1 SD: Abnormal Comprehensive Metabolic Profile

Protocol: BTI-201



Subject

Parameter (Unit)

Study Visit

Sample Date/

Time

(DDMMMYYYY/

HH:MM)

Actual

Value

Change from

Baseline1

Reference

Ranges

High/ Low

Flag

Clinical

Significance

Abnormality

Description

XXX

Sodium (unit)

Day 2

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

H

NCS

Day 3 or 4

DDMMMYYYY/

HH:MM

xx

xx

xx, xx

L

CS

XXXXXXXXXXXXXXX

Etc.

Etc.


L = Below Normal Range, H = Above Normal Range, NCS = Not Clinically Significant; CS = Clinically Significant.



Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

5 of

83

Listing 16.2.8.3.2.2 MAD: Abnormal Comprehensive Metabolic Profile

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.8.3

.2.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

6 of

83

Listing 16.2.9.1 SD: Vital Signs

Protocol: BTI-201



Subjec

t

Parameter

(Unit)

Assessment

Performed –

Reason Not

Performed

Study Visit

Assessment

Date

(DDMMMYYYY)

Timepoint

Time

(HH:MM)

Actual

Value

Change

from

Baseline1

Investigator’s

Overall

Interpretation If Abnormal,

specify

XXX

Systolic

Blood

Pressure

(mmHg)

Yes

Screening

DDMMMYYYY

HH:MM

xx

Normal

Yes

Day 1

DDMMMYYYY

Pre-dose1

HH:MM

xx

Abnormal NCS

XXXXXXXXX

End of

Infusion

HH:MM

xx

xx

Abnormal NCS

XXXXXXXXX

Etc.

Etc.


NCS = Not Clinically Significant, CS = Clinically Significant



Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

7 of

83

Listing 16.2.9.2 MAD: Vital Signs

Protocol: BTI-201



Programming Note: Repeat Listing 16.2.9.1.1 for the MAD.

Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.9.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

8 of

83

Listing 16.2.10.1 SD: EKG

Protocol: BTI-201



Subjec

t

Parameter

(Unit)

Assessment

Performed –

Reason Not

Performed Study Visit

Assessment

Date

(DDMMMYYYY) Timepoint

Time

(HH:MM) Actual

Value

Mean

Actual

Value

Mean Change

from

Baseline1

Investigator’s

Overall

Interpretation

Worst

Investigator’s

Overall

Interpretation

If

Abnormal,

specify

XXX

Heart

Rate

(unit)

Yes

Screening

DDMMMYYYY

EKG 1

HH:MM

xx

Normal

EKG 2

HH:MM

xx

xx.x

Abnormal NCS

Abnormal NCS

XXXXXXXXX

Yes

Day 11

DDMMMYYYY

EKG 1

HH:MM

xx

Abnormal NCS

EKG 2

HH:MM

xx

xx.x

Abnormal NCS

Abnormal NCS

XXXXXXXXX

Yes

Day 28 /

Early

Termination

DDMMMYYYY

EKG 1

HH:MM

xx

Abnormal NCS

EKG 2

HH:MM

xx

xx.x

xx.x

Abnormal CS

Abnormal NCS

XXXXXXXXX

etc.

etc.


NCS = Not Clinically Significant, CS = Clinically Significant



Prog

ram

min

g N

ote:

In

clud

e al

l par

amet

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

9 of

83

Listing 16.2.10.2 MAD: EKG

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.10.

1 fo

r MAD

. In

clud

e al

l par

amet

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

0 of

83

Listing 16.2.11.1 SD: Physical Examination

Protocol: BTI-201



Subject

Assessment

Performed –

Reason Not

Performed

Visit

Date/Time Physical

Examination

performed

(DDMMMYYYY)

Body System

Result

If Abnormal,

specify

XXX

Yes

Screening

DDMMMYYYY/ HH:MM

Skin

Normal

HEENT

Normal

….

Abnormal NCS

ZZZZZZZZZZZZ

Musculoskeletal

Abnormal NCS

ZZZZZZZZZZZZ

Yes

Day 1

DDMMMYYYY/ HH:MM

Skin

Normal

HEENT

Normal

….

Abnormal NCS

ZZZZZZZZZZZZ

Musculoskeletal

Abnormal NCS

ZZZZZZZZZZZZ

Yes

Day 2

DDMMMYYYY/ HH:MM

Skin

Normal

…

HEENT

Normal

XXX

No -

ZZZZZZZZ

….

…

Musculoskeletal

Normal

Note: NCS = Not Clinically Significant, CS = Clinically Significant



Prog

ram

min

g N

ote:

In

clud

e al

l tim

e po

ints

and

all

para

met

ers.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

1 of

83

Listing 16.2.11.2 MAD: Physical Examination

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.9.1

1.1

for M

AD.

Incl

ude

all t

ime

poin

ts a

nd a

ll pa

ram

eter

s.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

2 of

83

Listing 16.2.12.1.1 SD: Outcome Prediction Models CURB-65

Protocol: BTI-201



Subject

Study Visit

Test

Performed –

Reason Not

Performed

Visit Date

Confusion of

New Onset

Blood Urea

Nitrogen

Respiratory

Rate

(breaths/min)

Systolic/

Diastolic

BP (mmHg)

Age

(years)

CURB-65 Score

Actual

Value

Change from

Baseline1

XXXXX

Screening1

Yes

DDMMMYYYY

xx

xx (unit)

xx

xxx/ xx

xx

xx

Day 3/4

Yes

DDMMMYYYY

xx

xx (unit)

xx

xxx/ xx

xx

xx

xx

Day 7

Yes

DDMMMYYYY

xx

xx (unit)

xx

xxx/ xx

xx

xx

xx

Day 14

Yes

DDMMMYYYY

xx

xx (unit)

xx

xxx/ xx

xx

xx

xx

Day 28 /

Early

Termination

Yes

DDMMMYYYY

xx

xx (unit)

xx

xxx/ xx

xx

xx

xx

Etc.




Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

3 of

83

Listing 16.2.12.1.2 MAD: Outcome Prediction Models CURB-65

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.12.

1.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

4 of

83

Listing 16.2.12.2.1 SD: Outcome Prediction Models PSI (Port Score)

Protocol: BTI-201



Subject

Study Visit

Test Performed –

Reason Not

Performed

Visit Date

PSI Score

PSI Class

Actual Value

Change from

Baseline1

XXXXX

Screening1

Yes

DDMMMYYYY

xx

I

Day 3/4

Yes

DDMMMYYYY

xx

xx

II

Day 7

Yes

DDMMMYYYY

xx

xx

III

Day 14

Yes

DDMMMYYYY

xx

xx

IV

Day 28 / Early

Termination

Yes

DDMMMYYYY

xx

xx

V

Etc.




Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

5 of

83

Listing 16.2.12.2.2 MAD: Outcome Prediction Models PSI (Port Score)

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.12.

2.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

6 of

83

Listing 16.2.12.3.1 SD: Outcome Prediction Models SOFA Score

Protocol: BTI-201



Subject

Study Visit

Test Performed –


Visit Date

SOFA Score

Actual Value

Change from

Baseline1

XXXXX

Screening1

Yes

DDMMMYYYY

xx

Day 3/4

Yes

DDMMMYYYY

xx

xx

Day 7

Yes

DDMMMYYYY

xx

xx

Day 14

Yes

DDMMMYYYY

xx

xx

Day 28 / Early

Termination

Yes

DDMMMYYYY

xx

xx

Etc.




Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

7 of

83

Listing 16.2.12.3.2 MAD: Outcome Prediction Models SOFA Score

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.12.

3.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

8 of

83

Listing 16.2.12.4.1 SD: Outcome Prediction Models MMSE Score

Protocol: BTI-201



Subject

Study Visit

Test Performed –


Visit Date

MMSE Score

Actual Value

Change from

Baseline1

XXXXX

Screening1

Yes

DDMMMYYYY

xx

Day 3/4

Yes

DDMMMYYYY

xx

xx

Day 7

Yes

DDMMMYYYY

xx

xx

Day 14

Yes

DDMMMYYYY

xx

xx

Day 28 / Early

Termination

Yes

DDMMMYYYY

xx

xx

etc.




Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

9 of

83

Listing 16.2.12.4.2 MAD: Outcome Prediction Models MMSE Score

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.12.

4.1

for M

AD.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 8

0 of

83

Listing 16.2.13.1 SD: Concomitant Medications

Protocol: BTI-201



Subject

Number

CM#

Drug Name/ATC3/PT

Indication

Start Date/

Stop Date

(DDMMMYYYY)

Ongoing

Dose

Unit

Frequency

Route

XXX

1




To treat AE: AE#

DDMMMYYYY /

DDMMMYYYY

No

XX

Unit

YYYYYY

ZZZZZ

2




Other: YYYYYY

DDMMMYYYY /

DDMMMYYYY

No

XX

Unit

YYYYYY

ZZZZZ

XXX

1




Other: YYYYYY

DDMMMYYYY /

DDMMMYYYY

No

XX

Unit

YYYYYY

ZZZZZ

2




Other: YYYYYY

DDMMMYYYY /

Ongoing

Yes

XX

Unit

YYYYYY

ZZZZZ

XXX

1




To treat AE: AE#

DDMMMYYYY /

DDMMMYYYY

No

XX

Unit

YYYYYY

ZZZZZ

Etc.

Note: Concomitant medications are medications taken at least once after first study-drug administration.

WHO-DD, xxxxxxxxxx



Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 8

1 of

83

Listing 16.2.13.2 MAD: Concomitant Medication

Protocol: BTI-201



Pr

ogra

mm

ing

Not

e:

Repe

at L

istin

g 16

.2.9

.13.

1 fo

r MAD

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 8

2 of

83

Listing 16.2.14.1 SD: Hospitalization Follow-Up

Protocol: BTI-201



Subject

Discharged

from

Hospital

Length of Hospital Stay

ICU Stay

Intubation

Administered

Antibiotics

Require

Vasopressors

Date and Time of

Hospitalization

Admission due to

CAP (DDMMMYYYY/

HH:MM)

Date/ Time of

Discharge/ Study

Exit

(DDMMMYYYY/

HH:MM)

Number

of

Hours

Yes/No

Number of

Days

Yes/No

Number of

Days

XXX

Yes

DDMMMYYYY/ HH:MM DDMMMYYYY/ HH:MM

xx

Yes

xx

Yes

xx

Yes

No

XXX

Yes


xx

Yes

xx

No

No

No

XXX

Yes


xx

No

No

No

No

XXX

No


xx

No

No

No

No

etc.

Note: Length of stay in hospital is defined as the date and time of discharge/date of study exit (23:59 PM) -




Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

List

ings

, Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 8

3 of

83

Listing 16.2.14.2 MAD: Hospitalization Follow-Up

Protocol: BTI-201



Prog

ram

min

g N

ote:

Re

peat

List

ing

16.2

.14.

1 fo

r MAD

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

of 1

8

BTI-2

01: M

ock

Figu

res:

Tab

le o

f Con

tent

s Figures

Figu

re 1

4.2.

1.1

Indi

vid

ual

pGSN

Pla

sma

Conce

ntra

tion

s (n

g/mL

) (Li

near

sca

le)

by D

ay ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 3

Fi

gure

14.

2.1.

2 In

divid

ual

pGSN

Pla

sma

Conce

ntra

tion

s (n

g/mL

) (Se

mi-l

ogar

ithm

ic)

by Da

y ...

......

......

......

......

......

......

......

......

......

......

......

......

......

4

Figu

re 1

4.2.

2.1

Indi

vid

ual

Esti

mate

d Pl

asma

rhu-pG

SN P

lasm

a Co

nce

ntra

tion

s (n

g/mL

) bas

ed o

n Ch

ange

s fr

om Pr

e-In

ject

ion

(L

inea

r sc

ale)

by

Day

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 5

Figu

re 1

4.2.

2.2

Indi

vid

ual

Esti

mate

d Pl

asma

rhu-pG

SN P

lasm

a Co

nce

ntra

tion

s (n

g/mL

) bas

ed o

n th

e Do

uble

Delt

a An

alys

is

(Lin

ear

scal

e) b

y Da

y ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.....

6 Fi

gure

14.

2.3.

1 Me

an (+

/-SD

) pG

SN P

lasm

a Con

cent

rati

ons

(ng/

mL) (

Line

ar s

cale

) by

Day

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 7

Figu

re 1

4.2.

3.2

Mean

(+

/-SD

) pG

SN P

lasm

a Con

cent

rati

ons

(ng/

mL) b

ased

on

Chan

ges

from

Pre-In

ject

ion

(Li

nea

r sc

ale)

by

Day

(Sem

i-lo

gari

thmi

c) b

y D

ay ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

. 8

Figu

re 1

4.2.

4.1

Mean

(+

/-SD

) Es

tima

ted

Plasm

a rh

u-pG

SN P

lasm

a Con

cent

rati

ons

(ng/

mL) b

ased

on

Chan

ges

from

Pre-In

ject

ion

(L

inea

r sc

ale)

by

Day

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 9

Figu

re 1

4.2.

4.2

Mean

(+

/-SD

) Es

tima

ted

Plasm

a rh

u-pG

SN P

lasm

a Con

cent

rati

ons

(ng/

mL) b

ased

on

the

Doub

le De

lta

Anal

ysis

(L

inea

r sc

ale)

by

Day

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

10

Figu

re 1

4.3.

1.1

SD:

Kap

lan-

Meie

r Pl

ot o

f Ove

rall

Sur

viva

l Ti

me ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 1

1 Fi

gure

14.

3.1.

2 MA

D: Ka

plan

-Mei

er P

lot

of Ov

eral

l Su

rviv

al T

ime

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 1

2 Fi

gure

14.

3.2.

1 SD

: Kap

lan-

Meie

r Pl

ot o

f Len

gth

of S

tay

in H

ospit

al (

hour

s) ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

... 1

2 Fi

gure

14.

3.2.

2 MA

D: Ka

plan

-Mei

er P

lot

of Le

ngth

of

Stay

in

Hospi

tal

(hou

rs)

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

... 1

4 Fi

gure

14.

3.3.

1 SD

: Kap

lan-

Meie

r Pl

ot o

f Dur

atio

n of

ICU

Sta

y ...

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

14

Figu

re 1

4.3.

3.2

MAD:

Ka

plan

-Mei

er P

lot

of Du

rati

on o

f IC

U St

ay ..

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 1

6 Fi

gure

14.

3.4.

1 SD

: Kap

lan-

Meie

r Pl

ot o

f Dur

atio

n of

Int

ubat

ion

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.... 1

7 Fi

gure

14.

3.4.

2 MA

D: Ka

plan

-Mei

er P

lot

of Du

rati

on o

f In

tuba

tion

.....

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

......

.. 18

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 2

of 1

8 GE

NER

AL C

OM

MEN

TS

Nam

es o

f Tre

atm

ent G

roup

s:

SD:

rh

u-pG

SN 6

mg/

kg.

M

AD:

rhu-

pGSN

6 m

g/kg

;

rhu-

pGSN

12

mg/

kg;

rh

u-pG

SN 2

4 m

g/kg

.

N

ames

of P

K sa

mpl

ing

times

: Da

y 1

(SD

and

MAD

) & D

ay 3

(MAD

)

Pre-

inje

ctio

n

5 to

10

min

s

2h

8h

12h

16

h

24h

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 3

of 1

8 Figure 14.2.1.1 Individual pGSN Plasma Concentrations (ng/mL) (Linear scale) by Day

Protocol: BTI-201

PK Populations

Day

1 Clinical cut-off date: DDMMMYYYY


Prog

ram

min

g N

ote:

Th

e x-

axis

will

repr

esen

t the

act

ual s

tudy

tim

e in

hou

rs (0

– 2

4 ho

urs)

. Th

e y-

axis

will

repr

esen

t the

pGS

N P

lasm

a Co

ncen

trat

ions

(ng/

mL)

. The

y-a

xis w

ill b

e on

the

linea

r sca

le.

All s

ubje

cts w

ill b

e re

pres

ente

d on

a si

ngle

pag

e. E

ach

dose

leve

l will

be

pres

ente

d as

a d

istin

ct li

ne ty

pe. A

sepa

rate

figu

re w

ill b

e cr

eate

d fo

r eac

h Da

y. S

D an

d M

AD

subj

ects

will

be

pres

ente

d on

the

sam

e pa

ge b

y Da

y.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 4

of 1

8 Figure 14.2.1.2 Individual pGSN Plasma Concentrations (ng/mL) (Semi-logarithmic) by Day

Protocol: BTI-201

PK Populations

Day



Prog

ram

min

g N

ote:

Th

e x-

axis

will

repr

esen

t the

act

ual s

tudy

tim

e in

hou

rs (0

– 2

4 ho

urs)

. Th

e y-

axis

will

repr

esen

t the

pGS

N P

lasm

a Co

ncen

trat

ions

(ng/

mL)

. The

y-a

xis w

ill b

e on

the

log

scal

e.

All s

ubje

cts w

ill b

e re

pres

ente

d on

a si

ngle

pag

e. E

ach

dose

leve

l will

be

pres

ente

d as

a d

istin

ct li

ne ty

pe. A

sepa

rate

figu

re w

ill b

e cr

eate

d fo

r eac

h Da

y. S

D an

d M

AD

subj

ects

will

be

pres

ente

d on

the

sam

e pa

ge b

y Da

y.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 5

of 1

8 Figure 14.2.2.1 Individual Estimated Plasma rhu-pGSN Plasma Concentrations (ng/mL) based on Changes from Pre-Injection

(Linear scale) by Day

Protocol: BTI-201

PK Populations

Day



Prog

ram

min

g N

ote:

Th

e x-

axis

will

repr

esen

t the

act

ual s

tudy

tim

e in

hou

rs (0

– 2

4 ho

urs)

. Th

e y-

axis

will

repr

esen

t the

Est

imat

ed P

lasm

a rh

u-pG

SN C

once

ntra

tions

(ng/

mL)

. The

y-a

xis w

ill b

e on

the

linea

r sca

le.

All s

ubje

cts w

ill b

e re

pres

ente

d on

a si

ngle

pag

e. E

ach

dose

leve

l will

be

pres

ente

d as

a d

istin

ct li

ne ty

pe. A

sepa

rate

figu

re w

ill b

e cr

eate

d fo

r eac

h Da

y. S

D an

d M

AD

subj

ects

will

be

pres

ente

d on

the

sam

e pa

ge b

y Da

y.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 6

of 1

8 Figure 14.2.2.2 Individual Estimated Plasma rhu-pGSN Plasma Concentrations (ng/mL) based on the Double Delta Analysis


Protocol: BTI-201

PK Populations

Day



Prog

ram

min

g N

ote:

Th

e x-

axis

will

repr

esen

t the

nom

inal

stud

y tim

e in

hou

rs (0

– 2

4 ho

urs)

. Th

e y-

axis

will

repr

esen

t the

Est

imat

ed P

lasm

a rh

u-pG

SN C

once

ntra

tions

(ng/

mL)

. The

y-a

xis w

ill b

e on

the

linea

r sca

le.

All s

ubje

cts w

ill b

e re

pres

ente

d on

a si

ngle

pag

e. E

ach

dose

leve

l will

be

pres

ente

d as

a d

istin

ct li

ne ty

pe. A

sepa

rate

figu

re w

ill b

e cr

eate

d fo

r eac

h Da

y. S

D an

d M

AD

subj

ects

will

be

pres

ente

d on

the

sam

e pa

ge b

y Da

y.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 7

of 1

8 Figure 14.2.3.1 Mean (+/-SD) pGSN Plasma Concentrations (ng/mL) (Linear scale) by Day

Protocol: BTI-201

PK Populations

Day



Prog

ram

min

g N

ote:

Th

e x-

axis

will

repr

esen

t the

nom

inal

stud

y tim

e in

hou

rs (0

– 2

4 ho

urs)

. Th

e y-

axis

will

repr

esen

t the

mea

n pG

SN P

lasm

a Co

ncen

trat

ions

(ng/

mL)

per

Dos

e le

vel.

Whi

sker

s will

be

incl

uded

to re

flect

the

SDs.

The

y-a

xis w

ill b

e on

the

linea

r sc

ale.

All

trea

tmen

ts w

ill b

e re

pres

ente

d on

a si

ngle

pag

e. E

ach

dose

leve

l will

be

pres

ente

d as

a d

istin

ct li

ne ty

pe.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 8

of 1

8 Figure 14.2.3.2 Mean (+/-SD) pGSN Plasma Concentrations (ng/mL) based on Changes from Pre-Injection

(Linear scale) by Day (Semi-logarithmic) by Day

Protocol: BTI-201

PK Populations

Day



Prog

ram

min

g N

ote:

Th

e x-

axis

will

repr

esen

t the

nom

inal

stud

y tim

e in

hou

rs (0

– 2

4 ho

urs)

. Th

e y-

axis

will

repr

esen

t the

mea

n rh

u-pG

SN P

lasm

a Co

ncen

trat

ions

(ng/

mL)

per

Dos

e le

vel.

Whi

sker

s will

be

incl

uded

to re

flect

the

SDs.

The

y-a

xis w

ill b

e on

the

log

scal

e. A

ll tr

eatm

ents

will

be

repr

esen

ted

on a

sing

le p

age.

Eac

h do

se le

vel w

ill b

e pr

esen

ted

as a

dist

inct

line

type

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 9

of 1

8 Figure 14.2.4.1 Mean (+/-SD) Estimated Plasma rhu-pGSN Plasma Concentrations (ng/mL) based on Changes from Pre-Injection


Protocol: BTI-201

PK Populations

Day



Prog

ram

min

g N

ote:

Th

e x-

axis

will

repr

esen

t the

nom

inal

stud

y tim

e in

hou

rs (0

– 2

4 ho

urs)

. Th

e y-

axis

will

repr

esen

t the

mea

n Es

timat

ed P

lasm

a rh

u-pG

SN P

lasm

a Co

ncen

trat

ions

(ng/

mL)

per

Dos

e le

vel.

Whi

sker

s will

be

incl

uded

to re

flect

the

SDs.

The

y-a

xis

will

be

on th

e lin

ear s

cale

. All

trea

tmen

ts w

ill b

e re

pres

ente

d on

a si

ngle

pag

e. E

ach

dose

leve

l will

be

pres

ente

d as

a d

istin

ct li

ne ty

pe.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

0 of

18

Figure 14.2.4.2 Mean (+/-SD) Estimated Plasma rhu-pGSN Plasma Concentrations (ng/mL) based on the Double Delta Analysis


Protocol: BTI-201

PK Populations

Day



Prog

ram

min

g N

ote:

Th

e x-

axis

will

repr

esen

t the

nom

inal

stud

y tim

e in

hou

rs (0

– 2

4 ho

urs)

. Th

e y-

axis

will

repr

esen

t the

mea

n Es

timat

ed P

lasm

a rh

u-pG

SN P

lasm

a Co

ncen

trat

ions

(ng/

mL)

per

Dos

e le

vel.

Whi

sker

s will

be

incl

uded

to re

flect

the

SDs.

The

y-a

xis

will

be

on th

e lin

ear s

cale

. All

trea

tmen

ts w

ill b

e re

pres

ente

d on

a si

ngle

pag

e. E

ach

dose

leve

l will

be

pres

ente

d as

a d

istin

ct li

ne ty

pe.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

1 of

18

Figure 14.3.1.1 SD: Kaplan-Meier Plot of Overall Survival Time

Protocol: BTI-201

Safety Population






Prog

ram

min

g N

ote:

rh

u -pG

SN a

nd c

ombi

ned

Plac

ebo

trea

tmen

ts w

ill b

e pr

esen

ted

on o

ne g

raph

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

2 of

18

Figure 14.3.1.2 MAD: Kaplan-Meier Plot of Overall Survival Time

Protocol: BTI-201

Safety Population






Prog

ram

min

g N

ote:

rh

u -pG

SN a

nd c

ombi

ned

Plac

ebo

trea

tmen

ts w

ill b

e pr

esen

ted

on o

ne g

raph

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

3 of

18

Figure 14.3.2.1 SD: Kaplan-Meier Plot of Length of Stay in Hospital (hours)

Protocol: BTI-201

Safety Population

Note: Length of stay in hospital is defined as the date and time of discharge/date of study exit (23:59 PM ) -




Prog

ram

min

g N

ote:

rh

u -pG

SN a

nd c

ombi

ned

Plac

ebo

trea

tmen

ts w

ill b

e pr

esen

ted

on o

ne g

raph

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

4 of

18

Figure 14.3.2.2 MAD: Kaplan-Meier Plot of Length of Stay in Hospital (hours)

Protocol: BTI-201

Safety Population

Note: Length of stay in hospital is defined as the date and time of discharge/date of study exit (23:59 PM ) -




Prog

ram

min

g N

ote:

rh

u -pG

SN a

nd c

ombi

ned

Plac

ebo

trea

tmen

ts w

ill b

e pr

esen

ted

on o

ne g

raph

.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

5 of

18

Figure 14.3.3.1 SD: Kaplan-Meier Plot of Duration of ICU Stay

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

rh

u-pG

SN a

nd c

ombi

ned

Plac

ebo

trea

tmen

ts w

ill b

e pr

esen

ted

on o

ne g

raph

. Onl

y in

clud

e su

bjec

ts th

at st

ayed

in th

e IC

U.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

6 of

18

Figure 14.3.3.2 MAD: Kaplan-Meier Plot of Duration of ICU Stay

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

rh

u-pG

SN a

nd c

ombi

ned

Plac

ebo

trea

tmen

ts w

ill b

e pr

esen

ted

on o

ne g

raph

. Onl

y in

clud

e su

bjec

ts th

at st

ayed

in th

e IC

U.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

7 of

18

Figure 14.3.4.1 SD: Kaplan-Meier Plot of Duration of Intubation

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

rh

u-pG

SN a

nd c

ombi

ned

Plac

ebo

trea

tmen

ts w

ill b

e pr

esen

ted

on o

ne g

raph

. Onl

y in

clud

e su

bjec

ts th

at w

ere

intu

bate

d.

Prot

ocol

No:

BTI

-201

Do

cum

ent s

tatu

s: M

ock

EOS

Figu

res,

Fin

al V

2.0

Amen

dmen

t V1.

0 20

18-1

2-03

N

ovot

ech

– St

rictly

Con

fiden

tial

Pa

ge 1

8 of

18

Figure 14.3.4.2 MAD: Kaplan-Meier Plot of Duration of Intubation

Protocol: BTI-201

Safety Population



Prog

ram

min

g N

ote:

rh

u-pG

SN a

nd c

ombi

ned

Plac

ebo

trea

tmen

ts w

ill b

e pr

esen

ted

on o

ne g

raph

. Onl

y in

clud

e su

bjec

ts th

at w

ere

intu

bate

d.

Documents

STATISTICAL ANALYSIS PLAN Protocol No.: BT-201 · Protocol Number: BT-201 03 December 2018 Document status: Final SAP Version 2.0 Amendment 1.0 Novotech - Strictly Confidential Page