Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 74
Healthy volunteers: no

Brief summary:
The purpose of this research study is to determine if a change in inflammation or baseline inflammation seen on the ultrasound is a good indicator of how rheumatoid arthritis patients respond to TCZ 4mg/kg and whether early prediction of dose escalation is possible by utilizing ultrasound inflammatory measures.

Detailed description:
This is a 24-week, double blind open label clinical trial study to evaluate 57 active Rheumatoid Arthritis (RA) patients who have moderate to severe disease activity with total Power Doppler Ultrasound (PDUS) \>10 of 34 joints evaluated by Ultrasound (US) (at screening to enter into the study). All patients will begin treatment with tocilizumab at a dose of 4mg/kg. Two study sites will recruit patients (UCLA and UF) using the same protocol, after standardizing US acquisition methods, as well as scoring. US synovitis scores will be acquired at screening, baseline, and pre-infusion at 4, 12, 16, and 24 weeks, to be able to determine whether change in pre-infusion synovitis score at 4 weeks can be used to predict change in disease activity at 12 weeks. This will provide evidence to whether such reading is useful in predicting which patients may require escalation of dose from 4 to 8 mg/kg. At 12 weeks, patients not meeting low disease activity within the 4mg/kg (disease activity score DAS28/ Erythrocyte Sedimentation Rate (ESR)-4item\<3.2) will increase the tocilizumab dose to 8mg/kg (maximum dose 800mg) in a blinded manner to enable evaluation of these US-focused objectives in the context of the current FDA-approved label. The ultrasound scorer will not know information about patient's disease activity (Tender Joint Count (TJC), Swollen Joint Count (SJC), labs etc) or if there was dose escalation at 12 weeks. The clinical assessor of disease activity will be blinded to the ultrasound scores. Additionally, the patient will also be blinded to dose escalation. If patients in the 4mg/kg arm achieve DAS28\<3.2 at 12 weeks, patients will continue with their current dose for the duration of the study. Please see the below Table for details on the blinding plan.

Arms:
arm 1: All subjects will receive tocilizumab.

Interventions: intervention 1: Tocilizumab
Intervention descriptions: intervention 1: All subjects will start at 4mg/kg. After 3 months, if DAS28 \> 3.2, dosage will be escalated to 8 mg/kg.

Protocol document:
Prot_SAP_000.pdf: 
7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 1 of 33 
9HUVLRQ'$7( 
8&/$3ULPDU\6LWH
8QLYHUVLW\RI)ORULGD6XEVLWH




6WXG\7LWOH
0XVFXORVNHOHWDO8OWUDVRXQGLQ3UHGLFWLQJ(DUO\'RVH7LWUDWLRQ
ZLWK7RFLOL]XPDE

6WXG\'UXJ
7RFLOL]XPDE$&7(05$

6XSSRUW3URYLGHG%\
*HQHQWHFK

,QYHVWLJDWRUV
9HHQD.5DQJDQDWK0'06
*XUMLW.DHOH\0%%605&3







7KLVSURWRFROWHPSODWHLVEHLQJVXSSOLHGE\*HQHQWHFK,QFIRUDVVLVWDQFHLQWKH
GHYHORSPHQWRILQYHVWLJDWRUVSRQVRUHG7RFLOL]XPDEVSHFLILFSURWRFROVDSSURYHG
E\*HQHQWHFK,QF3OHDVHHQVXUHWKDWWKHIROORZLQJVHFWLRQFRQWDLQLQJ
PDQGDWRU\ODQJXDJHLVLQFOXGHGLQ\RXUSURWRFRO
 6HFWLRQ±5HSRUWLQJRI$GYHUVH(YHQWV









6WXG\1XPEHU


0/

3URWRFRO9HUVLRQ'DWH
9HUVLRQ'HFHPEHU




7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 2 of 33 
9HUVLRQ'$7( 
7$%/(2)&217(176



,1752'8&7,21

'LVHDVH%DFNJURXQG

7RFLOL]XPDE%DFNJURXQG

2WKHU6WXG\'UXJV%DFNJURXQG

6WXG\5DWLRQDOH


2%-(&7,9(6

3ULPDU\$LP

([SORUDWRU\$LPV


678'<'(6,*1

'HVFULSWLRQRIWKH6WXG\

6WXG\6FKHPD

5DWLRQDOHIRUWKH6WXG\'HVLJQDQG'RVH

2XWFRPH0HDVXUHV

3ULPDU\2XWFRPH0HDVXUHV

6HFRQGDU\2XWFRPH0HDVXUHV

6DIHW\2XWFRPH0HDVXUHV
(QGRI6WXG\

678'<3238/$7,21

2YHUYLHZ

,QFOXVLRQ&ULWHULD

([FOXVLRQ&ULWHULD

,PPXQL]DWLRQGXULQJ7RFLOL]XPDEWKHUDS\

&ULWHULDIRU3UHPDWXUH:LWKGUDZDO


75($70(173/$1


678'<0(',&$7,21

7RFLOL]XPDE

7RFLOL]XPDE'RVDJHDQG$GPLQLVWUDWLRQ

7RFLOL]XPDE6WRUDJH

7RFLOL]XPDE2YHUGRVDJH


'26(02',),&$7,2172;,&,7<0$1$*(0(17

7RFLOL]XPDE


&5,7(5,$)2568%-(&7',6&217,18$7,21

7RFLOL]XPDE6SHFLILF&ULWHULD

*HQHUDO&ULWHULD


&5,7(5,$)25678'<',6&217,18$7,21

 &/,1,&$/$1'/$%25$725<(9$/8$7,216


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 3 of 33 
9HUVLRQ'$7( 
 3UH7UHDWPHQW(YDOXDWLRQV
 (YDOXDWLRQV'XULQJ7UHDWPHQW
 3RVW7UHDWPHQW(YDOXDWLRQV

 5(3257,1*2)$'9(56((9(176
 $GYHUVH(YHQWDQG5HSRUWLQJ'HILQLWLRQV
 5HSRUWLQJRI6HULRXV$GYHUVH(YHQWV$VVRFLDWHG:LWK7RFLOL]XPDE
3UHJQDQF\

 (9$/8$7,212)5(63216(

 67$7,67,&$/&216,'(5$7,216
 'HWHUPLQDWLRQRI6DPSOH6L]H
 3ODQQHG(IILFDF\(YDOXDWLRQV
 3ULPDU\(IILFDF\9DULDEOHV
 ([SORUDWRU\$QDO\VHV

 5(7(17,212)5(&25'6

5()(5(1&(6%,%/,2*5$3+<

$33(1',&(6

$SSHQGL[$ 6DIHW\5HSRUWLQJ)D[&RYHU6KHHW










7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 4 of 33 
9HUVLRQ'$7( 


,1752'8&7,21


'LVHDVH%DFNJURXQG

'HVSLWHVLJQLILFDQWDGYDQFHVPRUHVHQVLWLYH5$RXWFRPHPHDVXUHVDUHQHHGHG
WRDLGLQWKHUDSHXWLFGHFLVLRQPDNLQJ6RQRJUDSK\RUXOWUDVRXQG86DWRRO
LQFUHDVLQJO\DYDLODEOHLQUKHXPDWRORJLVW¶VRIILFHVLVDVHQVLWLYHLPDJLQJPRGDOLW\
ZKLFKFDQGHWHFWV\QRYLDOK\SHUWURSK\6+DQGSRZHU'RSSOHUV\QRYLWLVDFWLYLW\
3'867KLVVWXG\DLPVWRGHWHUPLQHLIHDUO\VRQRJUDSKLFPHDVXUHVZHHNV
LQ5$SDWLHQWVVWDUWHGRQPJNJRIWRFLOL]XPDE7&=FDQSUHGLFWZHHN
FKDQJHLQGLVHDVHDFWLYLW\DQGWKHQHHGIRUGRVHHVFDODWLRQ:HK\SRWKHVL]HWKDW
86PHDVXUHVRI6+DQG3'86FDQEHXVHGWRGHWHUPLQHZKHWKHUV\QRYLWLVLV
EHLQJFRQWUROOHGDVHDUO\DVWKHQGLQIXVLRQRI7&=UHVXOWLQJLQWKHDELOLW\WR
SUHGLFWZKLFKSDWLHQWVPD\QHHGWRWLWUDWHWKH7&=GRVHIURPPJNJWRPJNJ
PD[LPXPGRVHPJDQGWKDWWKLVDFWLRQZLOOUHVXOWLQEHWWHUDELOLW\WRWDLORU
GRVLQJWRDFKLHYHWKHRSWLPDOWUHDWPHQWUHVSRQVH


7RFLOL]XPDE%DFNJURXQG


7RFLOL]XPDE

7RFLOL]XPDE7&=IRUPHUO\NQRZQDVP\HORPDUHFHSWRUDQWLERG\05$LVD
UHFRPELQDQWKXPDQL]HGDQWLKXPDQPRQRFORQDODQWLERG\RIWKHLPPXQRJOREXOLQ
,J*VXEFODVVGLUHFWHGDJDLQVWWKH,/5DQGSURGXFHGE\UHFRPELQDQW'1$
WHFKQRORJ\&OLQLFDOHIILFDF\DQGVDIHW\VWXGLHVRI7&=KDYHEHHQFRQGXFWHGRU
DUHRQJRLQJLQYDULRXVGLVHDVHDUHDVLQFOXGLQJDGXOWRQVHW5$V\VWHPLFRQVHW
MXYHQLOHLGLRSDWKLFDUWKULWLVDQGSRO\DUWLFXODUMXYHQLOHLGLRSDWKLFDUWKULWLV

7KHKDOIOLIHRI7&=LVDSSUR[LPDWHO\GD\V7KH7&=H[SRVXUHVZHUHVWDEOH
RYHU\HDUVRIWUHDWPHQW7KHREVHUYHGPHDQ6'&WURXJKDWPJNJ,9
ZDVDWZHHNDQGDWZHHN7KHREVHUYHGPHDQ
6'&WURXJKDWPJNJZDVDWZHHNDQGDWZHHN


7KH5RFKHFOLQLFDOGHYHORSPHQWSURJUDPLQDGXOW5$FRPSULVHGILYHSLYRWDO
3KDVHWULDOVDQGWZRRSHQODEHOORQJWHUPWUHDWPHQWH[WHQVLRQVWXGLHV

)XUWKHULQIRUPDWLRQRQ7&=FDQEHIRXQGLQWKH,QYHVWLJDWRU¶V%URFKXUH,%
 

2WKHU6WXG\'UXJV%DFNJURXQG
1$


6WXG\5DWLRQDOH


7KH86)'$ODEHOLQJIRU$FWHPUDLQGLFDWHVXVHLQ5$SDWLHQWVUHIUDFWRU\WRRU
QRWUHVSRQGLQJWRDWOHDVW71)LQKLELWRUDQGDOVRUHFRPPHQGVWKDWWKHVWDUWLQJ
GRVHEHPJNJHYHU\ZNV7KHUHVXOWVRIWKH5$',$7(WULDOSURYLGHHYLGHQFH


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 5 of 33 
9HUVLRQ'$7( 
WKDWWKHPJNJGRVHLVXQOLNHO\WRUHVXOWLQORZGLVHDVHDFWLYLW\RUUHPLVVLRQLQ
WKHVHSDWLHQWV7KHUHIRUHPDLQWDLQLQJSDWLHQWVRQPJNJPD\GHOD\WLPHO\
FOLQLFDOUHVSRQVHVLPSRUWDQWIRULPSURYLQJLQIXQFWLRQ>@,QWKH7$0$5$VWXG\
FRQGXFWHGLQ*HUPDQ\71),5DQG'0$5',5SDWLHQWVZHUHWUHDWHGZLWKLQWKH
VDPHSURWRFRO71),5SDWLHQWVWUHDWHGZLWKPJNJDFFRUGLQJWR(8ODEHO
VKRZHGFOLQLFDOO\PHDQLQJIXOLPSURYHPHQWDVDOVRVHHQLQWKH86>@EXWOHVV
FRPSDUHGWR'0$5',5SDWLHQWVIXUWKHUVXSSRUWLQJWKHLPSRUWDQFHRIWKH
PJNJGRVH>@:HSURSRVHWRXVHPXVFXORVNHOHWDOXOWUDVRXQGWRH[DPLQH
LQLWLDOUHVSRQVHWR7&=WRGHWHUPLQHZKHWKHUWKHHDUO\HIIHFWRQV\QRYLWLVLV
SUHGLFWLYHRIWKHOLNHOLKRRGRIDFKLHYLQJDUHVSRQVHLQSDWLHQWVUHFHLYLQJWKH
PJNJGRVHDQGZKHWKHUWKLVHIIHFWWKHQFRUUHODWHVZLWKWLPLQJDQGPDJQLWXGHRI
UHVSRQVH

0XVFXORVNHOHWDO8OWUDVRXQG

0XVFXORVNHOHWDOXOWUDVRXQGXVHE\UKHXPDWRORJLVWVLVUDSLGO\JURZLQJLQWKH86$
>@&RPSDUHGWRRWKHUDGYDQFHGLPDJLQJWHFKQLTXHVLWLVDQLQH[SHQVLYHQRQ
LUUDGLDWLQJWHFKQLTXH6RQRJUDSK\FDQEHXWLOL]HGDWSRLQWRIFDUHDQGGRHVQRW
UHTXLUHXVHRIFRQWUDVWWRGHWHFWYDVFXODULW\$UHFHQW$&5ZKLWHSDSHURXWOLQHG
WKHFXUUHQWVWDWXVRIWKHXVHRIVRQRJUDSK\LQ$PHULFDQ5KHXPDWRORJ\SUDFWLFH
7KLVSDSHUDQGRWKHUVKDYHVXPPDUL]HGWKHYDOLGLW\RIXVHRIPXVFXORVNHOHWDO
XOWUDVRXQGLQ5$FOLQLFDOWULDOVVWXG\LQJWKHUHVSRQVHWRWKHUDSHXWLFDJHQWV>@
:KLOVWVRQRJUDSK\LVPRUHVHQVLWLYHWKDQ[UD\LQGHWHFWLQJHURVLRQVLWKDVWKH
DGGHGDGYDQWDJHDWLQIHUULQJLQIODPPDWLRQLQV\QRYLDOWLVVXHVE\GHWHFWLQJEORRG
IORZLQWLVVXHVZLWKRXWWKHXVHRIFRQWUDVWDJHQWV

5DGLRJUDSKLFDVVHVVPHQWVRIMRLQWVSDFHQDUURZLQJDQGHURVLRQVRIWKH
KDQGVIHHWPHDVXUHVRIGDPDJHDUHFRQVLGHUHGWKHJROGVWDQGDUGLPDJLQJ
RXWFRPHPHDVXUHPHQWODUJHO\EHFDXVHWKHVHPHDVXUHVDUHYDOLGDWHGWR
PHDVXUHFKDQJHLQUDQGRPL]HGFRQWUROOHGWULDOV5&7VZLWKFKDQJHVKRZQWR
EHDVVRFLDWHGZLWKIXQFWLRQDQGGLVDELOLW\+RZHYHUWKHDGYHQWRIELRORJLFDJHQWV
KDVUHYROXWLRQL]HGWKHWUHDWPHQWRI5$WRWKHSRLQWWKDWLQRUGHUWRVKRZD
GLIIHUHQFHEHWZHHQELRORJLFWUHDWPHQWVDUPVZLWKUDGLRJUDSKVUHTXLUHVDODUJH
VDPSOHVL]HDQGLPSRUWDQWO\ODFNRIVHQVLWLYLW\GRHVQ¶WDOORZXVHWRIDFLOLWDWH
WUHDWPHQWGHFLVLRQV$GGLWLRQDOFRQVLGHUDWLRQIRUWUHDWPHQWGHFLVLRQVLVWKDW
FOLQLFDOFRPSRVLWHPHDVXUHVVXFKDV'$6&'$,DQG5$3,'PD\QRW
DGHTXDWHO\UHIOHFWWKHWRWDOLW\RILQWUDDUWLFXODULQIODPPDWLRQFRQWULEXWLQJWRMRLQW
GDPDJH7KHXVHRIPXVFXORVNHOHWDO86LQGHWHFWLQJV\QRYLDOYDVFXODULW\DQG
K\SHUWURSK\LVUDSLGO\EHFRPLQJDYDOXDEOHLPDJLQJPRGDOLW\WRVHQVLWLYHO\
DVVHVVWKHUDSHXWLFUHVSRQVHLQ5$>@

7KHSHUVLVWHQFHRISRZHU'RSSOHU86VLJQDO3'86IRUYDVFXODULW\ZLWKLQWKH
MRLQWPD\SUHGLFWSURJUHVVLRQRIHURVLYHFKDQJH,QDVPDOOFRKRUWRI5$
SDWLHQWVWUHDWHGZLWK7&=DWPJNJPD[LPXPGRVHPJIRURQH\HDU+DPD
HWDOVXJJHVWVWKDW3'86VLJQDOFKDQJHPLUURUHGFOLQLFDOLPSURYHPHQWDQG
UDGLRJUDSKLFSURJUHVVLRQRIHURVLRQVZDVDVVRFLDWHGZLWKSUHVHQFHRI3'86
VLJQDO>@6LPLODUILQGLQJVKDYHEHHQUHSRUWHGE\RWKHULQYHVWLJDWRUVZKR


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 6 of 33 
9HUVLRQ'$7( 
WUHDWHGSDWLHQWVZLWKDFWLYH5$ZLWKQRWRQO\7&=EXWDOVRRWKHUELRORJLFDJHQWV
>@

6RQRJUDSK\PD\DOVREHXVHIXOLQDVVHVVLQJUHVSRQVHZKHUHVXSSUHVVLRQRI
3'86VLJQDODIWHUDGPLQLVWUDWLRQRIELRORJLFDJHQWVVXJJHVWVUHVSRQVHWR
WKHUDS\>@DQGSHUVLVWHQFHRI'RSSOHUVLJQDOPD\SUHGLFWWKHULVNRI
SURJUHVVLYHHURVLYHGLVHDVH,WLVWKLVIHDWXUHWKDWZHK\SRWKHVL]HZLOOEHXVHIXO
LQGHWHUPLQLQJZKLFKSDWLHQWVPD\QRWUHVSRQGWRPJNJWKXVUHTXLULQJDQ
HVFDODWLRQLQWKHUDS\WRDFKLHYHDQDFFHSWDEOHFOLQLFDOUHVSRQVH.XPHHWDO
GHPRQVWUDWHGWKHUDSLGUHVSRQVHWRPJNJPD[LPXPGRVHPJ
7RFLOL]XPDELQELRORJLFDOWKHUDS\QDLYH5$SDWLHQWVZKRZHUHQRQUHVSRQVLYHWR
ORZGRVHSUHGQLVRQHDQGPHWKRWUH[DWH7KHLQYHVWLJDWRUVZHUHDEOHWRSUHGLFW
'$6UHVSRQVHDWZHHNVEDVHGRQ'RSSOHUDFWLYLW\DWWZRZHHNV1RQ
UHVSRQGHUVGLGQRWVKRZDQ\FKDQJHLQ'RSSOHUDFWLYLW\DWWZRZHHNV>@

7KXVWKHUHLVVLJQLILFDQWSRWHQWLDOIRUWKHXVHRIDVHQVLWLYHLPDJLQJPHDVXUHWR
RSWLPL]H7&=GRVLQJUHJLPHQV7KHUHKDYHEHHQQRVWXGLHVZKLFKKDYH
HYDOXDWHGWKHXWLOLW\LQXOWUDVRXQGPHDVXUHPHQWVWRGHWHUPLQHHVFDODWLRQRI
WRFLOL]XPDEWKHUDS\IURPDGRVLQJRIPJNJWRPJNJPD[LPXPGRVHPJ

:HSURSRVHDQRSHQODEHOFOLQLFDOVWXG\WRHYDOXDWHWKHSRWHQWLDOXVHIXOQHVVRI
86DVDQHDUO\LQGLFDWRULQPHDVXULQJUHVSRQVHWRHVFDODWLRQGRVLQJRI
WRFLOL]XPDE


2%-(&7,9(6


3ULPDU\$LP
7RGHWHUPLQHLIXOWUDVRXQGSRZHU'RSSOHUV\QRYLWLVVFRUHVDWZHHNVRUDW
EDVHOLQHFDQSURYLGHHDUO\HYLGHQFHWRSUHGLFWFKDQJHVLQGLVHDVHDFWLYLW\DW
ZHHNVIROORZXSLQ5$SDWLHQWVWUHDWHGZLWKPJNJRI7&=

3ULPDU\+\SRWKHVLV:HK\SRWKHVL]HWKDWWKHFKDQJHLQ86SRZHU'RSSOHU
V\QRYLDOVFRUHVIURPEDVHOLQHWRZHHNVRUEDVHOLQH3'86ZLOOFRUUHODWHZLWK
FKDQJHLQ'$6VFRUHVDWZN


([SORUDWRU\$LPV
7RH[DPLQHLIXOWUDVRXQGSRZHU'RSSOHUV\QRYLWLVVFRUHVDWRUZHHNV
FDQSUHGLFWFKDQJHVLQGLVHDVHDFWLYLW\DWZHHNVIROORZXSLQ5$SDWLHQWV
WUHDWHGZLWKPJNJPD[LPXPGRVHPJRI7&=

([SORUDWRU\+\SRWKHVLV:LWKWKHXQGHUVWDQGLQJWKDWSDWLHQWVZKRUHTXLUHG
GRVHHVFDODWLRQWRPJNJPD[LPXPGRVHPJE\GHILQLWLRQZHUHOHVV
UHVSRQVLYHWR7&=PJNJZHZLOOH[DPLQHWKHFRUUHODWLRQRIFKDQJHLQ86
SRZHU'RSSOHUV\QRYLDOVFRUHVIURPZNVWRZNVDQGZN3'86ZLWK
'$6VFRUHVIURPZNVWRZNV:HK\SRWKHVL]HWKDWLQWKLVVXEFRKRUWRI
SDWLHQWVZKRGRVHHVFDODWHGWRPJNJPD[LPXPGRVHPJ3'86ZLOODOVR
EHSUHGLFWLYHRIUHVSRQVHWRWKHUDS\VLPLODUWRSULPDU\DLP



7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 7 of 33 
9HUVLRQ'$7( 
7RDVVHVVLIXOWUDVRXQGSRZHU'RSSOHUV\QRYLWLVVFRUHVDWEDVHOLQHDQG
FKDQJHEHWZHHQEDVHOLQHDQGZHHNVFDQSUHGLFWDFKLHYHPHQWRIORZGLVHDVH
DFWLYLW\'$6DWZHHNVIROORZXSLQ5$SDWLHQWVWUHDWHGZLWKPJNJRI
7&=,QDGGLWLRQWRGHWHUPLQHLIXOWUDVRXQGSRZHU'RSSOHUV\QRYLWLVVFRUH
FKDQJHEHWZHHQDQGZHHNVRUZHHN3'86VFRUHVFDQSUHGLFW
DFKLHYHPHQWRIORZGLVHDVHDFWLYLW\'$6DWZHHNVIROORZXSLQ5$
SDWLHQWVWUHDWHGZLWKPJNJPD[LPXPGRVHPJRI7&=)LQDOO\WRHYDOXDWH
WKHUHODWLRQVKLSEHWZHHQZHHNSRZHU'RSSOHUV\QRYLWLVDVZHHNV
FRUUHODWHVZLWKZHHN'$6

([SORUDWRU\+\SRWKHVLV:HK\SRWKHVL]HWKDWHDUO\FKDQJHLQ3'86RU
EDVHOLQH3'86ZLOOFRUUHODWHZLWKDWWDLQPHQWRIORZGLVHDVHDFWLYLW\'$6
7KHVWXG\ZDVQRWSRZHUHGWRDFKLHYHWKLVDLPZKLFKLQDQLPSRUWDQW
FRQVLGHUDWLRQ

7RHYDOXDWHWKHUHODWLRQVKLSEHWZHHQXOWUDVRXQG3'86DQGSK\VLFLDQMRLQW
DVVHVVPHQWVIRUVLPLODUMRLQWV

([SORUDWRU\+\SRWKHVLV:HK\SRWKHVL]HWKDWWKHUHZLOOEHDVLJQLILFDQW
FRUUHODWLRQEHWZHHQXOWUDVRXQGH[DPLQDWLRQVFRUHVIRUHDFKMRLQWDQG
SK\VLFLDQMRLQWDVVHVVPHQWV


678'<'(6,*1 
 
 

'HVFULSWLRQRIWKH6WXG\

 6WXG\6FKHPD

7KLVLVDZHHNGRXEOHEOLQGRSHQODEHOFOLQLFDOWULDOVWXG\WRHYDOXDWH
DFWLYH5$SDWLHQWVZKRKDYHPRGHUDWHWRVHYHUHGLVHDVHDFWLYLW\ZLWKWRWDO
3'86!RIMRLQWVHYDOXDWHGE\86DWVFUHHQLQJWRHQWHULQWRWKHVWXG\$OO
SDWLHQWVZLOOEHJLQWUHDWPHQWZLWKWRFLOL]XPDEDWDGRVHRIPJNJ7ZRVWXG\
VLWHVZLOOUHFUXLWSDWLHQWV8&/$DQG8)XVLQJWKHVDPHSURWRFRODIWHU
VWDQGDUGL]LQJ86DFTXLVLWLRQPHWKRGVDVZHOODVVFRULQJ86V\QRYLWLVVFRUHV
ZLOOEHDFTXLUHGDWVFUHHQLQJEDVHOLQHDQGSUHLQIXVLRQDWDQG
ZHHNVWREHDEOHWRGHWHUPLQHZKHWKHUFKDQJHLQSUHLQIXVLRQV\QRYLWLVVFRUHDW
ZHHNVFDQEHXVHGWRSUHGLFWFKDQJHLQGLVHDVHDFWLYLW\DWZHHNV7KLVZLOO
SURYLGHHYLGHQFHWRZKHWKHUVXFKUHDGLQJLVXVHIXOLQSUHGLFWLQJZKLFKSDWLHQWV
PD\UHTXLUHHVFDODWLRQRIGRVHIURPWRPJNJ$WZHHNVSDWLHQWVQRW
PHHWLQJORZGLVHDVHDFWLYLW\ZLWKLQWKHPJNJGLVHDVHDFWLYLW\VFRUH
'$6(65LWHPZLOOLQFUHDVHWKHWRFLOL]XPDEGRVHWRPJNJPD[LPXP
GRVHPJLQDEOLQGHGPDQQHUWRHQDEOHHYDOXDWLRQRIWKHVH86IRFXVHG
REMHFWLYHVLQWKHFRQWH[WRIWKHFXUUHQW)'$DSSURYHGODEHO7KHXOWUDVRXQG
VFRUHUZLOOQRWNQRZLQIRUPDWLRQDERXWSDWLHQW¶VGLVHDVHDFWLYLW\7-&6-&ODEV
HWFRULIWKHUHZDVGRVHHVFDODWLRQDWZHHNV7KHFOLQLFDODVVHVVRURIGLVHDVH
DFWLYLW\ZLOOEHEOLQGHGWRWKHXOWUDVRXQGVFRUHV$GGLWLRQDOO\WKHSDWLHQWZLOODOVR
EHEOLQGHGWRGRVHHVFDODWLRQ,ISDWLHQWVLQWKHPJNJDUPDFKLHYH'$6


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 8 of 33 
9HUVLRQ'$7( 
DWZHHNVSDWLHQWVZLOOFRQWLQXHZLWKWKHLUFXUUHQWGRVHIRUWKHGXUDWLRQRIWKH
VWXG\3OHDVHVHHWKHEHORZ7DEOHIRUGHWDLOVRQWKHEOLQGLQJSODQ

%OLQGLQJ3ODQ


&OLQLFDO
$VVHVVRU
8OWUDVRXQG
6FRUHU
3DWLHQW
&RRUGLQDWRU
3KDUPDF\
0RQLWRU
%OLQGHGWR
(VFDODWLRQ
<(6
<(6
<(6
12
12
12
%OLQGHGWR
&OLQLFDO
$VVHVVPHQW
12
<(6
12
12
1$
1$
%OLQGHGWR86
$VVHVVPHQW
<(6
12
12
12
1$
1$

7KXVWKHRYHUDOOJRDOLVWRHYDOXDWHWKHSRWHQWLDOXVHIXOQHVVRI86DVDQHDUO\
LQGLFDWRULQPHDVXULQJUHVSRQVHWRHQDEOHWLPHO\HVFDODWLRQRIWKHUDS\ZLWK
WRFLOL]XPDE6LPLODUO\ZHZLOOHYDOXDWHLI86LQIODPPDWRU\VFRUHVDWZHHNV
FDQSURYLGHLQIRUPDWLRQWRSUHGLFWUHVSRQVHDWZHHNV

$WVFUHHQLQJWKHIROORZLQJGDWDZLOOEHUHFRUGHGIRUHDFKSDWLHQWDJHVH[5$
GLVHDVHGXUDWLRQUKHXPDWRLGIDFWRUVWDWXVDQWLF\FOLFFLWUXOOLQDWHGDQWLERG\
VWDWXVVPRNLQJVWDWXVDOFRKROFRQVXPSWLRQFRPRUELGLWLHVFXUUHQWGLVHDVH
PRGLI\LQJDQWLUKHXPDWLFGUXJV'0$5'VDQGSULRU'0$5'VELRORJLFDJHQWV

,QDGGLWLRQ86ZLOOEHSHUIRUPHGDWVFUHHQLQJ3DWLHQWVZLWKD3'86VFRUHRI
OHVVWKDQDWVFUHHQLQJZLOOEHH[FOXGHGIURPWKHVWXG\$GHWDLOHGUHYLHZRI
WKHLQFOXVLRQDQGH[FOXVLRQSDUDPHWHUVZLOOEHSHUIRUPHGSULRUWRHQUROOPHQWLQWR
WKHVWXG\3DWLHQWVZLOOKDYH86'$6(65LWHPDQG+$4DVVHVVPHQWV
SHUIRUPHGWKHVDPHGD\,QDGGLWLRQSDWLHQWVZLOOKDYHEORRGVWRUHGIRU
ELRPDUNHUDVVD\VDW8&/$86DVVHVVPHQWGHVFULEHGEHORZZLOOEHSHUIRUPHG
DWVFUHHQLQJEDVHOLQHDQGZHHNVXVLQJVWDQGDUGPHWKRGVIRU
DVVHVVLQJV\QRYLWLVDQGSRZHU'RSSOHU6HHEHORZIRUDGHWDLOHGDFFRXQWRIWKH
PHWKRGRORJ\IRU86VFRUHV&'$,'$6(65LWHPDQG(65ZLOOEH
DVVHVVHGDWWKHIROORZLQJYLVLWVVFUHHQLQJEDVHOLQHDQGZHHNV
7KHTXDOLW\RIOLIHPHDVXUH+$4',ZLOOEHDVVHVVHGDWWKHIROORZLQJYLVLWV
VFUHHQLQJEDVHOLQHDQGZHHNV$GYHUVHHYHQWVDQGVHULRXVDGYHUVH
HYHQWVZLOODOVREHUHFRUGHGDWHDFKYLVLWKV&53ZLOOEHGRQHDWWKHIROORZLQJ
YLVLWVVFUHHQLQJEDVHOLQHZHHNVDQGZHHNV

$WHQWU\LQWRWKHVWXG\DOOVWXG\VXEMHFWVZLOOUHFHLYHPJNJ7&=$IWHU
ZHHNVRIWUHDWPHQWSDWLHQWVZLOOKDYHDVVHVVPHQWRIGLVHDVHDFWLYLW\E\
'$6(65LWHP,ISDWLHQWVDFKLHYH'$6WKHQWKHGRVLQJRIPJNJ
ZLOOEHFRQWLQXHG,IWKH'$6!WKHQSDWLHQWVZLOOEHLQFUHDVHGWRPJNJ
GRVLQJPD[LPXPGRVHPJ6WXG\VXEMHFWVDQGWKHXOWUDVRQRJUDSKHUZLOOEH
EOLQGHGWRGRVHHVFDODWLRQDVVLJQPHQW





7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 9 of 33 
9HUVLRQ'$7( 
-RLQW866FRULQJ6\VWHPELODWZULVWVELODW0&3VELODW3,3VELODWHUDO
073.QHHV
-2,17
9,(:
3RZHU
'RSSOHU
6\QRYLWLV
%PRGH
6\QRYLDO
+\SHUWURSK\
:ULVWV%LODWHUDO
3RVLWLRQ'HJ
'RUVDO/RQJLWXGLQDO0LGOLQH
5DGLRFDUSDOLQWHUFDUSDO
;
;
:ULVW
'RUVDO/RQJ6KRUW
5DGLRXOQDUMRLQW
;
;
0&3V
3RVLWLRQ'HJ
'RUVDO/RQJDQG6KRUW
;
;
9RODU/RQJLWXGLQDO
;
;
3,3VDQG,3
'RUVDO9RODU/RQJLWXGLQDO
;
;
073V
'RUVDO/RQJLWXGLQDO
;
;
.QHHV%LODWHUDO
0HGLDO3DUDSDWHOODU$[LDO
2EOLTXH
;
;
/DWHUDO3DUDSDWHOODU$[LDO
2EOLTXH
;
;

86DVVHVVPHQWVZLOOEHSHUIRUPHGXVLQJWKHMRLQW86VFRUH7RGDWHQR
VLQJOH86VFRULQJV\VWHPKDVEHHQ\HWGHWHUPLQHGDVWKHSUHYDLOLQJPHWKRG
+RZHYHUVHYHUDO86VFRULQJV\VWHPVKDYHGHPRQVWUDWHGWKDWSRZHU'RSSOHU
V\QRYLWLVDQG%PRGHV\QRYLDOK\SHUWURSK\VFRUHVDUHVHQVLWLYHWRFKDQJH)RU
WKLVSURSRVDOVHOHFWLRQRIWKHVSHFLILFMRLQWVZDVEDVHGRQPD[LPL]LQJ
SUHFLVLRQUHOLDELOLW\DQGIHDVLELOLW\IRUXOWUDVRQRJUDSK\0RVW86VFRULQJ
V\VWHPVZHLJKKHDYLO\RQWKHKDQGVDQGZULVWV6RPHVWXGLHVGHPRQVWUDWHWKH
SUHVHQFHRIQRUPDODPRXQWVRIIOXLGDWWKHPHWDUVRSKDODQJHDO073MRLQWVDQG
IUHTXHQWSUHVHQFHRIGHIRUPLWLHVVXFKDVKDPPHUWRHV7KXVWKHVHMRLQWVZHUH
H[FOXGHG>@*UH\VFDOHV\QRYLDOK\SHUWURSK\DQGSRZHU'RSSOHUZLOOEH
DVVHVVHGIRUELODWHUDOZULVWVGRUVDO0&3VGRUVDODQGYRODUDQG3,3V
YRODU$OOWKHDERYHDUHDVZLOOEHH[DPLQHGZLWK%0RGHDQGSRZHU'RSSOHU
PRGHVRQRJUDSK\7DEOHDERYH6WDQGDUG20(5$&7GHILQLWLRQVZLOOEHXVHG
IRUHIIXVLRQDQGV\QRYLDOK\SHUWURSK\

2XUSULPDU\HQGSRLQWLVWKHFKDQJHLQSRZHU'RSSOHU86V\QRYLWLV3'86VFRUH
DWZHHNV(DFKLPDJHZLOOEHVFRUHGDVGHVFULEHGEHORZIRUDPD[LPXP
VFRUHRI:HZLOODOVRREWDLQV\QRYLDOK\SHUWURSK\%PRGHVFRUHVZLWKWKH
VDPHPD[LPXPVFRUHRIDVRXUVHFRQGDU\HQGSRLQW7KHLQWUDDUWLFXODU
SRZHU'RSSOHUVLJQDOVZLOOEHJUDGHGRQDVFDOHIURPWRDVIROORZV*UDGH
DEVHQWQRV\QRYLDOIORZ*UDGHPLOGLVRODWHGVLJQDOV*UDGHPRGHUDWH
JUHDWHUWKDQLVRODWHGVLJQDOVRUFRQIOXHQWVLJQDOLQOHVVWKDQKDOIRIWKHV\QRYLDO
DUHD*UDGHPDUNHGVLJQDOVLQPRUHWKDQKDOIRIWKHV\QRYLDODUHD%PRGH
JUH\VFDOHV\QRYLDOK\SHUWURSK\ZLOOEHJUDGHGVHPLTXDQWLWDWLYHO\IURPWRDV
IROORZV*UDGHDEVHQW*UDGHPLOG*UDGHPRGHUDWHDQG*UDGH
VHYHUH7KHWRWDOLQIODPPDWRU\86VFRUHZLOODGGWKHV\QRYLDOK\SHUWURSK\%
PRGHVFRUHVDQGSRZHU'RSSOHUVFRUHVLQRUGHUWRREWDLQDFRPSUHKHQVLYH
DVVHVVPHQWRIWKH86LQIODPPDWRU\EXUGHQ(DFKXOWUDVRQRJUDSKHU8&/$DQG
8)ZLOOUHUHDGWKH86LPDJHVREWDLQHGIRUWKHSDWLHQWVYLVLWV>EDVHOLQH


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 10 of 33 
9HUVLRQ'$7( 
ZHHNVZHHNVDQGZHHNV@6FRULQJRIWKHLPDJHVZLOOEHSHUIRUPHGDV
SHU20(5$&7JXLGHOLQHV,QWUDDQGLQWHUUHDGHUUHOLDELOLW\VFRUHVZLOOEH
GHWHUPLQHGDWWKHHQGRIWKHVWXG\7KHVDPHXOWUDVRQRJUDSKHUVKRXOGEH
REWDLQLQJWKHLPDJHVDQGVFRULQJLPDJHVDWHDFKVLWH,QFDVHRIDQHPHUJHQF\
ZKHUHWKHGHVLJQDWHGXOWUDVRQRJUDSKHUFDQQRWSHUIRUPWKHXOWUDVRXQGDEDFN
XSXOWUDVRQRJUDSKHUZLOOSHUIRUPWKHUHTXLUHGXOWUDVRXQG+RZHYHUZHDQWLFLSDWH
WKDWWKLVZLOOEHDQXQOLNHO\VFHQDULR

7KH86ZLOOEHSHUIRUPHGE\DUKHXPDWRORJLVWZLWKH[SHUWLVHLQPXVFXORVNHOHWDO
XOWUDVRXQGDQGLPDJHVZLOOEHGLJLWDOO\VDYHG7KHXOWUDVRXQGVFRUHUZLOOEH
EOLQGHGWRWKHFOLQLFDODVVHVVPHQWVDQGYLVDYHUVD

6WDQGDUGL]DWLRQRI$FTXLVLWLRQDQG,QWHU,QWUD5HDGHU5HOLDELOLW\
3ULRUWRHPEDUNLQJRQWKHUDQGRPL]HGFOLQLFDOWULDOLWLVQHFHVVDU\WKDWWKH
XOWUDVRQRJUDSKHUVDW8&/$DQGDW8)ERWKUHOLDEO\DFTXLUHDQGVFRUHWKHLPDJHV
LQDVLPLODUPDQQHU*RRGDJUHHPHQWRQLPDJHDFTXLVLWLRQDQGVFRULQJZLOOEH
UHTXLUHGSULRUWRWKHVWDUWRIWKHVWXG\7RDFKLHYHWKLVJRDODGD\
VWDQGDUGL]DWLRQRIDFTXLVLWLRQDQGVFRULQJRIWKHXOWUDVRXQGLPDJHVZLOOEH
SHUIRUPHG

%HIRUHWKHIDFHWRIDFHPHHWLQJWKHXOWUDVRQRJUDSKHUVZLOODFTXLUHLPDJHVDV
GHVFULEHGLQRXUVWDQGDUGRSHUDWLQJSURFHGXUH623IRUWKHTXDOLW\DQG
UHOLDELOLW\RILPDJHDFTXLVLWLRQ623GHVFULEHVVWDQGDUGL]DWLRQRIVSHFLILF
YDULDEOHVLQFOXGLQJURRPWHPSHUDWXUHXOWUDVRXQGIDFWRUV%PRGHJDLQSRZHU
'RSSOHUJDLQIUHTXHQF\HWFJHOXVHDQGRWKHUV7KH623ZLOOLQFOXGHD
UHIHUHQFHDWODVUHSUHVHQWLQJVFDQVIURPHDFKMRLQWDUHD%RWKVLWHVZLOOUHYLHZ
WKH623DQGDWODV7KHQWKHXOWUDVRQRJUDSKHUVZLOOREWDLQLPDJHVRQ
SDWLHQWVZKLFKZLOOEHVFRUHGE\DOOVRQRJUDSKLFLQYHVWLJDWRUV'XULQJD
WHOHFRQIHUHQFHDQ\JHQHUDOGLIIHUHQFHVZLOOEHGLVFXVVHGDQGUHVROYHG

,QRUGHUWRVWDQGDUGL]HWKH86VFRULQJSURFHVVWKHXOWUDVRQRJUDSKHUVZLOOPHHW
DWDPXWXDOO\FRQYHQLHQWORFDWLRQ7KHPRUQLQJRIWKHILUVWGD\XOWUDVRQRJUDSKHUV
ZLOOREWDLQLPDJHVDQGVFRUHSHUSURWRFRORQ5$SDWLHQWVLQDURXQGURELQ
DSSURDFK7KLVSURFHVVZLOOEHUHSHDWHGLQWKHHYHQLQJWKDWVDPHGD\,QWUDDQG
LQWHUUHDGHUUHOLDELOLW\ZLOOEHFDOFXODWHGODWHUWKDWHYHQLQJ,QDGGLWLRQWKH
VFRULQJRILPDJHVZLWKWKHKLJKHVWGLVFRUGDQFHZLOOEHIODJJHGIRUKLJKHVWSULRULW\
IRUGLVFXVVLRQIRUWKHIROORZLQJGD\7KHIODJJHGLPDJHVZLOOEHGLVFXVVHGWLOO
PXWXDODJUHHPHQWLVDFKLHYHG%\FRQYHQWLRQDQ,&&RI!LVFRQVLGHUHG
JRRGUHOLDELOLW\DQG!LVH[FHOOHQWUHOLDELOLW\,WLVRXUJRDOWRVWULYHIRUH[FHOOHQW
UHOLDELOLW\,IWKHUHDUHDUHDVRIGLVDJUHHPHQWLQVFRULQJFRQVHQVXVZLOOEH
UHDFKHGDQGUHSHDWVFRULQJZLOOEHSHUIRUPHGXQWLO,&&VDUHJRRG!>@

$GGLWLRQRISRWHQWLDOELRPDUNHUV7KURXJKRXWWKHVWXG\VHUXPSODVPDZDV
VWRUHGRQSDWLHQWVDWEDVHOLQHVFUHHQLQJDQGDWZHHNVDSSURSULDWHDSSURYDO
ZDVREWDLQHGIURP8&/$,5%:HZLOOHYDOXDWHWKHVHVDPSOHVE\DF\WRNLQH
SOH[SDQHO(RWD[LQ*0&6),)1Į,)1Ȗ,/ȕ,/,/S»S,/
,/,/,/5$,/,/5,/,/,/,/,/,30&30,*


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 11 of 33 
9HUVLRQ'$7( 
0,3Į0,3ȕ5$17(671)Į,QDGGLWLRQZHZLOOSHUIRUP+'/DQWLR[LGDQW
DFWLYLW\SDUDR[RQDVHDFWLYLW\DQG+'/$SR$,(/,6$



5DWLRQDOHIRUWKH6WXG\'HVLJQDQG'RVH
,WLVFOHDUWKDWPRUHVHQVLWLYH5$RXWFRPHPHDVXUHVDUHUHTXLUHGWRDLGLQ
WKHUDSHXWLFGHFLVLRQPDNLQJ7KLVVWXG\ZLOOGHWHUPLQHLIHDUO\XOWUDVRXQG86
SRZHU'RSSOHUV\QRYLWLVVFRUHVZHHNVDVHQVLWLYHPHDVXUHRIGLVHDVH
DFWLYLW\FDQSUHGLFWUHVSRQVHWRWKHUDS\ZHHNVLQ5$SDWLHQWVVWDUWHGRQ
WRFLOL]XPDE7&=DWPJNJ7KLVFRKRUWRI5$SDWLHQWVZLOOEHDWULVNRIMRLQW
GDPDJHDQGUHTXLUHGWRKDYH3'86!DWVFUHHQLQJWREHLQFOXGHGLQWKHVWXG\
7KXVLPSO\LQJWKDWHDUOLHUWLWUDWLRQRI7&=GRVHIURPPJNJWRPJNJ
PD[LPXPGRVHPJZLOOUHVXOWLQEHWWHUWUHDWPHQWUHVSRQVH


2XWFRPH0HDVXUHV

 3ULPDU\2XWFRPH0HDVXUHV
7RWDOSRZHU'RSSOHUV\QRYLWLVVFRUHRIMRLQWVUDQJH

 6HFRQGDU\2XWFRPH0HDVXUHV
7RWDO%PRGHV\QRYLDOK\SHUWURSK\VFRUHRIMRLQWVUDQJH
&RPSRVLWHRISRZHU'RSSOHUV\QRYLDOK\SHUWURSK\RIMRLQWVUDQJH

 6DIHW\2XWFRPH0HDVXUHV
6HULRXVDGYHUVHHYHQWV
$GYHUVHHYHQWV
/DERUDWRU\YDOXHV

(QGRI6WXG\
$IWHUWUHDWPHQWZLWK7&=IRUZHHNVDQGRQHVDIHW\IROORZXSHYDOXDWLRQWR
HYDOXDWHDQ\$(V


678'<3238/$7,21
 
 2YHUYLHZ

7KLVLVDQRSHQODEHO7&=VWXG\RIDSURVSHFWLYHFRKRUWRI5$SDWLHQWVWUHDWHG
LQLWLDOO\ZLWKPJNJWRFLOL]XPDE7&=RYHUZHHNV7KHRYHUDOOJRDOLVWR
GHWHUPLQHZKHWKHUFKDQJHLQ3'86FDQEHXVHGWRSURYLGHHDUO\LQIRUPDWLRQRQ
ZKLFKSDWLHQWVPD\EHFOLQLFDOUHVSRQGHUVDWODWHUWLPHSRLQWVDQGSHUPLWGRVH
HVFDODWLRQSUHLQIXVLRQ(OLJLEOHSDWLHQWVZLOOEHVWDUWHGRQPJNJ7&=HYHU\
ZNVDQGZLOOXQGHUJRXOWUDVRXQGH[DPRIMRLQWVDWVFUHHQEDVHOLQHDQG
SUHLQIXVLRQDQGF\FOHV3DWLHQWVZKRGRQRWDFKLHYHDWOHDVWD
'$6GHPRQVWUDWLQJFOLQLFDOLPSURYHPHQWE\ZHHNVZLOOEHGRVH
HVFDODWHGWRPJNJPD[LPXPGRVHPJLQDEOLQGHGPDQQHUGHVFULEHG
DERYH



7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 12 of 33 
9HUVLRQ'$7( 
$SSUR[LPDWHO\WZRWKLUGVRIWKHSDWLHQWVZLOOEHUHFUXLWHGIURP8&/$
0HGLFDO3OD]D>RYHUUKHXPDWRORJLVWV@DWWKH6DQWD0RQLFD8&/$EDVHGDGXOW
UKHXPDWRORJ\SUDFWLFHZLWKWKUHHIXOOWLPHDQGRQHSDUWWLPHUKHXPDWRORJLVWVZKR
VHHSDWLHQWVGD\VDZHHNDQGSDUWWLPHUKHXPDWRORJLVWV7KHUHZLOOEHD
VHFRQGVLWHDWWKH8QLYHUVLW\RI)ORULGDZKHUHWKHUHPDLQLQJRQHWKLUGRISDWLHQWV
ZLOOEHUHFUXLWHG


,QFOXVLRQ&ULWHULD

3DWLHQWVPXVWKDYHUKHXPDWRLGDUWKULWLV3DWLHQWVZLOOEHLQFOXGHGLQWKHWULDO
EDVHGRQWKHIROORZLQJFULWHULD

3DWLHQWPXVWPHHW$&5FULWHULD
$JH!\HDUVRIDJH
%DVHOLQH'$6(65!
6WDEOHFRQFRPLWDQW'0$5'VIRUPRUHWKDQPRQWKPHWKRWUH[DWH
OHIOXQRPLGHSODTXLQHOVXOIDVDOD]LQHRUQR'0$5'V+RZHYHULIWKHSDWLHQWLV
QRWRQ'0$5'KLVWRU\RI'0$5'XVHUHTXLUHG
D,IQRWRQ'0$5'DQGWKHSDWLHQWVDWLVILHVWKHDERYHVWDWHPHQWWKH
SDWLHQWFDQRSWIRUPRQRWKHUDS\ZLWKWRFLOL]XPDERUFRPELQDWLRQWKHUDS\25
E,IRQELRORJLFPRQRWKHUDS\FDQRSWIRUPRQRWKHUDS\ZLWKWRFLOL]XPDERU
'0$5'FRPELQDWLRQWKHUDS\LHSDWLHQWVFDQQRWEHRQELRORJLFZLWK7&=
3RZHU'RSSOHUVFRUHRI!DWVFUHHQLQJ

*HQHUDO0HGLFDO&RQFHUQV

x 1RUPDORUJDQIXQFWLRQH[FHSWLIDEQRUPDOGXHWRWKHGLVHDVHXQGHU
LQYHVWLJDWLRQ
x 0HQDQGZRPHQRIUHSURGXFWLYHSRWHQWLDOPXVWDJUHHWRXVHDQDFFHSWDEOH
PHWKRGRIELUWKFRQWUROGXULQJWUHDWPHQWDQGIRUVL[PRQWKVDIWHUFRPSOHWLRQ
RIWUHDWPHQW
x 6XEMHFWKDVSURYLGHGZULWWHQLQIRUPHGFRQVHQW


([FOXVLRQ&ULWHULD

$SDWLHQWZLOOEHH[FOXGHGLIWKHDQVZHUWRDQ\RIWKHIROORZLQJVWDWHPHQWVLV
³\HV´

*HQHUDO

0DMRUVXUJHU\LQFOXGLQJMRLQWVXUJHU\ZLWKLQZHHNVSULRUWREDVHOLQHRU
SODQQHGPDMRUVXUJHU\ZLWKLQPRQWKVDIWHUEDVHOLQH

([FOXGHG3UHYLRXVRU&RQFRPLWDQW7KHUDS\

 7UHDWPHQWZLWKDQ\LQYHVWLJDWLRQDODJHQWZLWKLQZHHNVRUKDOIOLYHVRI
WKHLQYHVWLJDWLRQDOGUXJZKLFKHYHULVORQJHURIEDVHOLQH
 3UHYLRXVWUHDWPHQWZLWKDQ\FHOOGHSOHWLQJWKHUDSLHVLQFOXGLQJ


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 13 of 33 
9HUVLRQ'$7( 
LQYHVWLJDWLRQDODJHQWVRUDSSURYHGWKHUDSLHVVRPHH[DPSOHVDUH
&$03$7+DQWL&'DQWL&'DQWL&'
 3UHYLRXVWUHDWPHQWZLWKDQWL&'DQGDQWL&'ZLWKLQPRQWKVRIVWDUW
RIWKHVWXG\
 7UHDWPHQWZLWKLQWUDYHQRXVJDPPDJOREXOLQSODVPDSKHUHVLVRU3URVRUED
FROXPQZLWKLQPRQWKVRIEDVHOLQH
 ,PPXQL]DWLRQZLWKDOLYHDWWHQXDWHGYDFFLQHZLWKLQZHHNVSULRUWR
EDVHOLQH
 3UHYLRXVWUHDWPHQWZLWK7&=
 $Q\SUHYLRXVWUHDWPHQWZLWKDON\ODWLQJDJHQWVVXFKDVFKORUDPEXFLORU
ZLWKWRWDOO\PSKRLGLUUDGLDWLRQ
 8VHRISUHGQLVRQH!PJDWEDVHOLQH


([FOXVLRQVIRU*HQHUDO6DIHW\

+LVWRU\RIVHYHUHDOOHUJLFRUDQDSK\ODFWLFUHDFWLRQVWRKXPDQKXPDQL]HG
RUPXULQHPRQRFORQDODQWLERGLHV
(YLGHQFHRIVHULRXVXQFRQWUROOHGFRQFRPLWDQWFDUGLRYDVFXODUQHUYRXV
V\VWHPSXOPRQDU\LQFOXGLQJREVWUXFWLYHSXOPRQDU\GLVHDVHUHQDO
KHSDWLFHQGRFULQHLQFOXGHXQFRQWUROOHGGLDEHWHVPHOOLWXVRU
JDVWURLQWHVWLQDOGLVHDVHLQFOXGLQJFRPSOLFDWHGGLYHUWLFXOLWLVXOFHUDWLYH
FROLWLVRU&URKQ¶VGLVHDVH
&XUUHQWOLYHUGLVHDVHDVGHWHUPLQHGE\SULQFLSDOLQYHVWLJDWRUXQOHVV
UHODWHGWRSULPDU\GLVHDVHXQGHULQYHVWLJDWLRQ
.QRZQDFWLYHFXUUHQWRUKLVWRU\RIUHFXUUHQWEDFWHULDOYLUDOIXQJDO
P\FREDFWHULDORURWKHULQIHFWLRQVLQFOXGLQJEXWQRWOLPLWHGWRWXEHUFXORVLV
DQGDW\SLFDOP\FREDFWHULDOGLVHDVH+HSDWLWLV%DQG&DQGKHUSHV]RVWHU
EXWH[FOXGLQJIXQJDOLQIHFWLRQVRIQDLOEHGV
$Q\PDMRUHSLVRGHRILQIHFWLRQUHTXLULQJKRVSLWDOL]DWLRQRUWUHDWPHQWZLWK
,9DQWLELRWLFVZLWKLQZHHNVRIEDVHOLQHRURUDODQWLELRWLFVZLWKLQZHHNV
SULRUWREDVHOLQH
$FWLYH7%UHTXLULQJWUHDWPHQWZLWKLQWKHSUHYLRXV\HDUV3DWLHQWVVKRXOG
EHVFUHHQHGIRUODWHQW7%DQGLISRVLWLYHWUHDWHGIROORZLQJORFDOSUDFWLFH
JXLGHOLQHVSULRUWRLQLWLDWLQJ7&=3DWLHQWVWUHDWHGIRUWXEHUFXORVLVZLWKQR
UHFXUUHQFHLQ\HDUVDUHSHUPLWWHG
3ULPDU\RUVHFRQGDU\LPPXQRGHILFLHQF\KLVWRU\RIRUFXUUHQWO\DFWLYH
XQOHVVUHODWHGWRSULPDU\GLVHDVHXQGHULQYHVWLJDWLRQ
(YLGHQFHRIDFWLYHPDOLJQDQWGLVHDVHPDOLJQDQFLHVGLDJQRVHGZLWKLQWKH
SUHYLRXV\HDUVLQFOXGLQJKHPDWRORJLFDOPDOLJQDQFLHVDQGVROLGWXPRUV
H[FHSWEDVDODQGVTXDPRXVFHOOFDUFLQRPDRIWKHVNLQRUFDUFLQRPDLQ
VLWXRIWKHFHUYL[XWHULWKDWKDVEHHQH[FLVHGDQGFXUHGRUEUHDVWFDQFHU
GLDJQRVHGZLWKLQWKHSUHYLRXV\HDUV
3UHJQDQWZRPHQRUQXUVLQJEUHDVWIHHGLQJPRWKHUV
3DWLHQWVZLWKUHSURGXFWLYHSRWHQWLDOQRWZLOOLQJWRXVHDQHIIHFWLYHPHWKRG
RIFRQWUDFHSWLRQ
+LVWRU\RIDOFRKROGUXJRUFKHPLFDODEXVHZLWKLQ\HDUSULRUWRVFUHHQLQJ
1HXURSDWKLHVRURWKHUFRQGLWLRQVWKDWPLJKWLQWHUIHUHZLWKSDLQ


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 14 of 33 
9HUVLRQ'$7( 
HYDOXDWLRQXQOHVVUHODWHGWRSULPDU\GLVHDVHXQGHULQYHVWLJDWLRQ
3DWLHQWVZLWKODFNRISHULSKHUDOYHQRXVDFFHVV
%RG\ZHLJKWRI!NJ

/DERUDWRU\([FOXVLRQFULWHULDDWVFUHHQLQJ
6HUXPFUHDWLQLQH!PJG/PRO/LQIHPDOHSDWLHQWVDQG!
PJG/PRO/LQPDOHSDWLHQWV3DWLHQWVZLWKVHUXPFUHDWLQLQH
YDOXHVH[FHHGLQJOLPLWVPD\EHHOLJLEOHIRUWKHVWXG\LIWKHLUHVWLPDWHG
JORPHUXODUILOWUDWLRQUDWHV*)5DUH!
$ODQLQHDPLQRWUDQVIHUDVH$/7RUDVSDUWDWHDPLQRWUDQVIHUDVH$67!
WLPHVXSSHUOLPLWRIQRUPDO8/1
7RWDO%LOLUXELQ!8/1
3ODWHOHWFRXQW[/PP
+HPRJORELQJ/JG/PPRO/
:KLWH%ORRG&HOOV[/PP
$EVROXWH1HXWURSKLO&RXQW[/PP
$EVROXWH/\PSKRF\WH&RXQW[/PP
3RVLWLYH+HSDWLWLV%V$JRU+HSDWLWLV&DQWLERG\
+,9SRVLWLYH


,PPXQL]DWLRQGXULQJ7&=WKHUDS\

/LYHYDFFLQHVFDQQRWEHJLYHQFRQFXUUHQWO\ZLWK7RFLOL]XPDEDVFOLQLFDOVDIHW\
KDVQRWEHHQHVWDEOLVKHG1RGDWDDUHDYDLODEOHRQWKHVHFRQGDU\WUDQVPLVVLRQ
RILQIHFWLRQIURPSHUVRQVUHFHLYLQJOLYHYDFFLQHVWRSDWLHQWVUHFHLYLQJ
7RFLOL]XPDE%HFDXVH,/LQKLELWLRQPD\LQWHUIHUHZLWKWKHQRUPDOLPPXQH
UHVSRQVHWRQHZDQWLJHQVSDWLHQWVVKRXOGEHEURXJKWXSWRGDWHRQDOO
UHFRPPHQGHGYDFFLQDWLRQVH[FHSWIRUOLYHYDFFLQHVSULRUWRLQLWLDWLRQRIWKHUDS\
ZLWK7RFLOL]XPDE

&ULWHULDIRU3UHPDWXUH:LWKGUDZDO

3DWLHQWVKDYHWKHULJKWWRZLWKGUDZIURPWKHVWXG\DWDQ\WLPHIRUDQ\UHDVRQ7KHUH
VKRXOGEHDQDWWHPSWWRKDYHDOOSDWLHQWVFRPSOHWHWKHZLWKGUDZDOYLVLWVRUVDIHW\
IROORZXSVDVGHWDLOHGLQWKH6FKHGXOHRI$VVHVVPHQWV

,IWKHSDWLHQWGHFLGHVWRSUHPDWXUHO\GLVFRQWLQXHVWXG\WUHDWPHQW³UHIXVHV
WUHDWPHQW´KHVKHVKRXOGEHDVNHGLIKHVKHFDQVWLOOEHFRQWDFWHGIRUIXUWKHU
LQIRUPDWLRQ7KHRXWFRPHRIWKDWGLVFXVVLRQVKRXOGEHGRFXPHQWHGLQERWKWKH
PHGLFDOUHFRUGVDQGLQWKH&5)$FRPSOHWHILQDOHYDOXDWLRQDWWKHWLPHRIWKH
SDWLHQW¶VZLWKGUDZDOVKRXOGEHPDGHZLWKDQH[SODQDWLRQRIZK\WKHSDWLHQWLV
ZLWKGUDZLQJIURPWKHVWXG\%HIRUHFDWHJRUL]LQJDSDWLHQWDVORVWWRIROORZXSWKH
LQYHVWLJDWRUPXVWDWWHPSWWRFRQWDFWWKHSDWLHQWRUDUHVSRQVLEOHUHODWLYHE\
WHOHSKRQHIROORZHGE\UHJLVWHUHGPDLOWRGHWHUPLQHLIDQ\QHZ$(VRFFXUUHGIROORZ
XSRIDQ\RQJRLQJ$(DQGWRHVWDEOLVKDVFRPSOHWHO\DVSRVVLEOHWKHUHDVRQIRUWKH
ZLWKGUDZDO

:KHQDSSOLFDEOHSDWLHQWVVKRXOGEHLQIRUPHGRIFLUFXPVWDQFHVXQGHUZKLFKWKHLU
SDUWLFLSDWLRQPD\EHWHUPLQDWHGE\WKHLQYHVWLJDWRUZLWKRXWWKHSDWLHQW¶VFRQVHQW7KH


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 15 of 33 
9HUVLRQ'$7( 
LQYHVWLJDWRUPD\ZLWKGUDZSDWLHQWVIURPWKHVWXG\LQWKHHYHQWRILQWHUFXUUHQWLOOQHVV
DGYHUVHHYHQWVWUHDWPHQWIDLOXUHODFNRIFRPSOLDQFHZLWKWKHVWXG\DQGRUVWXG\
SURFHGXUHVHJGRVLQJLQVWUXFWLRQVVWXG\YLVLWVRUDQ\UHDVRQZKHUHLWLVIHOWE\
WKHLQYHVWLJDWRUWKDWLWLVLQWKHEHVWLQWHUHVWRIWKHSDWLHQWWREHWHUPLQDWHGIURPWKH
VWXG\7KHUHDVRQVIRUZLWKGUDZDOPXVWEHGRFXPHQWHGDQGH[SODLQHGWRWKH
SDWLHQW

,IWKHUHDVRQIRUUHPRYDORIDSDWLHQWIURPWKHVWXG\LVDQDGYHUVHHYHQWWKHVSHFLILF
HYHQWZLOOEHUHFRUGHGRQWKH&5)7KHUHVKRXOGEHDQDWWHPSWWRIROORZWKHSDWLHQW
XQWLOWKHHYHQWKDVUHVROYHGRUVWDELOL]HG

$QH[FHVVLYHUDWHRIZLWKGUDZDOVFDQUHQGHUWKHVWXG\QRQLQWHUSUHWDEOHWKHUHIRUH
XQQHFHVVDU\ZLWKGUDZDORISDWLHQWVVKRXOGEHDYRLGHG6KRXOGDSDWLHQWGHFLGHWR
ZLWKGUDZDOOHIIRUWVZLOOEHPDGHWRFRPSOHWHDQGUHSRUWWKHREVHUYDWLRQVSULRUWR
ZLWKGUDZDODVWKRURXJKO\DVSRVVLEOH


75($70(173/$1

7KLVLVD3KDVH,9GRXEOHEOLQGUDQGRPL]HGFOLQLFDOWULDOZLWK7&=GRVHGPJNJ
HYHU\ZHHNVLQIXVLRQVIRUZHHNV3DWLHQWVZLOOVWHSXSWRPJNJPD[LPXP
GRVHPJRI7&=LIWKH\GRQRWDFKLHYHDJRDORI'$67KLVUHVHDUFK
VWXG\SURWRFRODOORZVWKHVXEMHFWWRUHFHLYHXSWRLQIXVLRQVRI7RFLOL]XPDE:H
HVWLPDWHHQUROOLQJSDWLHQWVSHUPRQWKDW8&/$DQGSDWLHQWVSHUPRQWKDWWKH
8QLYHUVLW\RI)ORULGDWKXVHQGLQJHQUROOPHQWLQDSSUR[LPDWHO\PRQWKV,WZDV
FULWLFDOWKDWZHDGGHGWKHVHFRQGVLWHLQRUGHUWRGHFUHDVHWKHWLPHRISDWLHQW
HQUROOPHQWZKLFKZRXOGKDYHEHHQ!PRQWKVZLWKRQHVLWH:HDQWLFLSDWHWKDW
WKHODVWYLVLWRIWKHODVWSDWLHQWZLOOEHDWPRQWKV

(YHQLIWKHWUHDWPHQWLVVKRZQWREHRIEHQHILWDGGLWLRQDOLQIXVLRQVRI
7RFLOL]XPDEEH\RQGWKDWDOORZHGLQWKHSURWRFROFDQQRWEHJLYHQWRWKHVXEMHFW
ZKLOHVKHKHLVSDUWLFLSDWLQJLQWKLVVWXG\


678'<0(',&$7,21


7RFLOL]XPDE

7RFLOL]XPDE$&7(05$LVDUHFRPELQDQWKXPDQL]HGDQWLKXPDQLQWHUOHXNLQ
,/UHFHSWRUPRQRFORQDODQWLERG\RIWKHLPPXQRJOREXOLQ,J*țJDPPD
NDSSDVXEFODVVZLWKDW\SLFDO+/SRO\SHSWLGHVWUXFWXUH(DFKOLJKWFKDLQDQG
KHDY\FKDLQFRQVLVWVRIDQGDPLQRDFLGVUHVSHFWLYHO\7KHIRXU
SRO\SHSWLGHFKDLQVDUHOLQNHGLQWUDDQGLQWHUPROHFXODUO\E\GLVXOILGHERQGV
7RFLOL]XPDEKDVDPROHFXODUZHLJKWRIDSSUR[LPDWHO\N'D
7RFLOL]XPDELVVXSSOLHGDVDVWHULOHSUHVHUYDWLYHIUHHVROXWLRQIRULQWUDYHQRXV
,9LQIXVLRQDWDFRQFHQWUDWLRQRIPJP/7RFLOL]XPDELVDFRORUOHVVWRSDOH
\HOORZOLTXLGZLWKDS+RIDERXW6LQJOHXVHYLDOVDUHDYDLODEOHFRQWDLQLQJ
PJP/PJP/RUPJP/RI7RFLOL]XPDE,QMHFWDEOHVROXWLRQV
RI7RFLOL]XPDEDUHIRUPXODWHGLQDQDTXHRXVVROXWLRQFRQWDLQLQJGLVRGLXP
SKRVSKDWHGRGHFDK\GUDWHDQGVRGLXPGLK\GURJHQSKRVSKDWHGHK\GUDWHDVD


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 16 of 33 
9HUVLRQ'$7( 
PPRO/SKRVSKDWHEXIIHUSRO\VRUEDWHPJP/DQGVXFURVH
PJP/

7RFLOL]XPDEZLOOEHSURYLGHGIUHHRIFKDUJHE\*HQHQWHFK7KH
6SRQVRU,QYHVWLJDWRURIWKHVWXG\ZLOOHQVXUHPDLQWHQDQFHRIFRPSOHWHDQG
DFFXUDWHUHFRUGVRIWKHUHFHLSWGLVSHQVDWLRQDQGGLVSRVDORUUHWXUQRIDOOVWXG\
GUXJLQDFFRUGDQFHZLWK&RGHRI)HGHUDO5HJXODWLRQV&)53DUW
DQGDQG*HQHQWHFKUHTXLUHPHQWV

 7RFLOL]XPDE'RVDJHDQG$GPLQLVWUDWLRQ

7KHUHFRPPHQGHGGRVHRIWRFLOL]XPDEIRUDGXOWSDWLHQWVLVPJNJDQGWLWUDWLRQ
XSWRPJNJPD[LPXPGRVHPJJLYHQRQFHHYHU\IRXUZHHNVDVDQ,9
LQIXVLRQ7RFLOL]XPDEFDQEHXVHGDORQHRULQFRPELQDWLRQZLWK07;DQGRURWKHU
'0$5'V

7RFLOL]XPDEVKRXOGEHGLOXWHGWRP/E\DKHDOWKFDUHSURIHVVLRQDOZLWKVWHULOH
ZYVRGLXPFKORULGHVROXWLRQXVLQJDVHSWLFWHFKQLTXH7RFLOL]XPDELV
UHFRPPHQGHGIRU,9LQIXVLRQRYHUKRXU

)RULQGLYLGXDOVZKRVHERG\ZHLJKWLVPRUHWKDQNJGRVHVH[FHHGLQJ
PJSHULQIXVLRQDUHQRWUHFRPPHQGHG

2QHYLDOFRQWDLQLQJPJ7&=RUWZRYLDOVFRQWDLQLQJPJ7&=ZLOOEH
UHTXLUHGIRUHDFKNJERG\ZHLJKWWRDFKLHYHDQPJNJPD[LPXPGRVH
PJGRVH7KHQXPEHURIYLDOVWREHXVHGGHSHQGVRQWKHSDWLHQW¶VERG\
ZHLJKWDVIROORZV

2QHPJYLDORUWZRPJYLDOVLVXVHGIRUSDWLHQWVZLWKDERG\
ZHLJKWNJ

7ZRPJYLDOVRUIRXUPJYLDOVDUHXVHGIRUSDWLHQWVZLWKDERG\
ZHLJKW!NJFRPELQDWLRQRIWKHPJDQGPJYLDOVPD\EHXVHGEXWWKH
WRWDOGRVHVKRXOGQRWH[FHHGPJ

 7RFLOL]XPDE6WRUDJH

7RFLOL]XPDEVKRXOGQRWEHXVHGDIWHUWKHH[SLU\GDWH(;3VKRZQRQWKHSDFN

)RUYLDOV6WRUHEHWZHHQ&±&GRQRWIUHH]H.HHSWKHFRQWDLQHULQWKH
RXWHUFDUWRQLQRUGHUWRSURWHFWIURPOLJKW

)RUSUHSDUHGLQIXVLRQVROXWLRQ7KHSUHSDUHGLQIXVLRQVROXWLRQRIWRFLOL]XPDELV
SK\VLFDOO\DQGFKHPLFDOO\VWDEOHLQZYVRGLXPFKORULGHVROXWLRQDW&IRU
KRXUV

)URPDPLFURELRORJLFDOSRLQWRIYLHZWKHSUHSDUHGLQIXVLRQVKRXOGEHXVHG
LPPHGLDWHO\,IQRWXVHGLPPHGLDWHO\LQXVHVWRUDJHWLPHVDQGFRQGLWLRQVSULRUWR


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 17 of 33 
9HUVLRQ'$7( 
XVHDUHWKHUHVSRQVLELOLW\RIWKHXVHUDQGZRXOGQRWEHORQJHUWKDQKRXUVDW
&±&XQOHVVGLOXWLRQKDVWDNHQSODFHLQFRQWUROOHGDQGYDOLGDWHGDVHSWLF
FRQGLWLRQV

 7RFLOL]XPDE2YHUGRVDJH

7KHUHDUHOLPLWHGGDWDDYDLODEOHRQRYHUGRVHVZLWK7RFLOL]XPDE2QHFDVHRI
DFFLGHQWDORYHUGRVHZDVUHSRUWHGLQZKLFKDSDWLHQWZLWKPXOWLSOHP\HORPD
UHFHLYHGDGRVHRIPJNJ1RDGYHUVHGUXJUHDFWLRQVZHUHREVHUYHG1R
VHULRXVDGYHUVHGUXJUHDFWLRQVZHUHREVHUYHGLQKHDOWK\YROXQWHHUVZKR
UHFHLYHGVLQJOHGRVHVRIXSWRPJNJDOWKRXJKDOOSDWLHQWVDWWKHKLJKHVW
GRVHRIPJNJGHYHORSHGGRVHOLPLWLQJQHXWURSHQLD

,QFDVHRIDQRYHUGRVHLWLVUHFRPPHQGHGWKDWWKHSDWLHQWEHPRQLWRUHGIRU
VLJQVDQGV\PSWRPVRIDGYHUVHUHDFWLRQV3DWLHQWVZKRGHYHORSDGYHUVH
UHDFWLRQVVKRXOGUHFHLYHDSSURSULDWHV\PSWRPDWLFWUHDWPHQW


'26(02',),&$7,2172;,&,7<0$1$*(0(17

$QXPEHURIPHDVXUHVZLOOEHWDNHQWRHQVXUHWKHVDIHW\RISDWLHQWVSDUWLFLSDWLQJ
LQWKLVVWXG\7KHVHPHDVXUHVZLOOEHDGGUHVVHGWKURXJKH[FOXVLRQFULWHULDVHH
6HFWLRQDQGURXWLQHPRQLWRULQJDVIROORZV

3DWLHQWVHQUROOHGLQWKLVVWXG\ZLOOEHHYDOXDWHGFOLQLFDOO\DQGZLWKVWDQGDUG
ODERUDWRU\WHVWVEHIRUHDQGGXULQJWKHLUSDUWLFLSDWLRQLQWKLVVWXG\6DIHW\
HYDOXDWLRQVZLOOFRQVLVWRIPHGLFDOLQWHUYLHZVUHFRUGLQJRIDGYHUVHHYHQWV
SK\VLFDOH[DPLQDWLRQVEORRGSUHVVXUHDQGODERUDWRU\PHDVXUHPHQWV6XEMHFWV
ZLOOEHHYDOXDWHGIRUDGYHUVHHYHQWVDOOJUDGHVVHULRXVDGYHUVHHYHQWVDQG
DGYHUVHHYHQWVUHTXLULQJVWXG\GUXJLQWHUUXSWLRQRUGLVFRQWLQXDWLRQDWHDFKVWXG\
YLVLWIRUWKHGXUDWLRQRIWKHLUSDUWLFLSDWLRQLQWKHVWXG\


7RFLOL]XPDE

2SSRUWXQLVWLF,QIHFWLRQVDQG6HULRXV,QIHFWLRQV

3K\VLFLDQVVKRXOGH[HUFLVHFDXWLRQZKHQFRQVLGHULQJWKHXVHRI7&=LQSDWLHQWV
ZLWKDKLVWRU\RIUHFXUULQJLQIHFWLRQRUZLWKXQGHUO\LQJFRQGLWLRQVHJGLDEHWHV
ZKLFKPD\SUHGLVSRVHSDWLHQWVWRLQIHFWLRQV7RFLOL]XPDEVKRXOGQRWEH
DGPLQLVWHUHGLQSDWLHQWVZLWKDFWLYHLQIHFWLRQ7KHHIIHFWVRI7&=RQ&53
QHXWURSKLOVDQGWKHVLJQVDQGV\PSWRPVRILQIHFWLRQVKRXOGEHFRQVLGHUHGZKHQ
HYDOXDWLQJDSDWLHQWIRUDSRWHQWLDOLQIHFWLRQ
 
9LJLODQFH IRU WLPHO\ GHWHFWLRQ RI VHULRXV LQIHFWLRQ LV UHFRPPHQGHG IRUSDWLHQWV
UHFHLYLQJELRORJLFDJHQWVIRUWUHDWPHQWRIPRGHUDWHWRVHYHUH5$DVVLJQVDQG
V\PSWRPV RI DFXWH LQIODPPDWLRQ PD\ EH OHVVHQHG GXH WR VXSSUHVVLRQ RI WKH
DFXWH SKDVH UHDFWLRQ 3DWLHQWV PXVW EH LQVWUXFWHG WR FRQWDFW WKHLU SK\VLFLDQ
LPPHGLDWHO\ZKHQDQ\V\PSWRPVVXJJHVWLQJLQIHFWLRQDSSHDULQRUGHUWRDVVXUH
UDSLGHYDOXDWLRQDQGDSSURSULDWHWUHDWPHQW


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 18 of 33 
9HUVLRQ'$7( 

,I D SDWLHQW GHYHORSV D VHULRXV LQIHFWLRQ DGPLQLVWUDWLRQ RI 7&= LV WR EH
LQWHUUXSWHG XQWLO WKH LQIHFWLRQ LV FRQWUROOHG 7KH FOLQLFLDQ VKRXOG FRQVLGHU WKH
EHQHILWULVNEHIRUHUHVXPLQJWUHDWPHQWZLWKWRFLOL]XPDE

*DVWURLQWHVWLQDO3HUIRUDWLRQV

7LPHO\ GLDJQRVLV DQG DSSURSULDWH WUHDWPHQW PD\ UHGXFH WKH SRWHQWLDO IRU
FRPSOLFDWLRQV RI GLYHUWLFXOLWLV DQG WKXV UHGXFH WKH ULVN RI *, SHUIRUDWLRQV
7KHUHIRUH SDWLHQWV VKRXOG EH PDGH DZDUH RI WKH V\PSWRPDWRORJ\ SRWHQWLDOO\
LQGLFDWLYH RI GLYHUWLFXODU GLVHDVH DQG WKH\ VKRXOG EH LQVWUXFWHG WR DOHUW WKHLU
KHDOWKFDUHSURYLGHUDVVRRQDVSRVVLEOHLIWKHVHV\PSWRPVDULVH,QSDWLHQWVZLWK
DKLVWRU\RIV\PSWRPDWLFGLYHUWLFXORVLVGLYHUWLFXOLWLVRUFKURQLFXOFHUDWLYHORZHU*,
GLVHDVH VXFK DV &URKQ¶V GLVHDVH XOFHUDWLYH FROLWLV RU RWKHU FKURQLF ORZHU *,
FRQGLWLRQVWKDWPLJKWSUHGLVSRVHWRSHUIRUDWLRQVWKHFOLQLFLDQVKRXOGFRQVLGHUWKH
EHQHILWULVN EHIRUH XVLQJ 7&=  'LVFRQWLQXDWLRQ RI 7&= LV UHFRPPHQGHG IRU
SDWLHQWVZKRGHYHORS*,SHUIRUDWLRQV

'HP\HOLQDWLQJ'LVRUGHUV

7KH LPSDFW RI WUHDWPHQW ZLWK 7&= RQ GHP\HOLQDWLQJ GLVRUGHUV LV QRW NQRZQ
HYHQWVZHUHUDUHO\UHSRUWHG3DWLHQWVVKRXOGEHFORVHO\PRQLWRUHGIRUVLJQVDQG
V\PSWRPV SRWHQWLDOO\ LQGLFDWLYH RI FHQWUDO GHP\HOLQDWLQJ GLVRUGHUV  3K\VLFLDQV
VKRXOG H[HUFLVH FDXWLRQ LQ FRQVLGHULQJ WKH XVH RI 7&= LQ SDWLHQWV ZLWK SUH
H[LVWLQJ RU UHFHQW RQVHW GHP\HOLQDWLQJ GLVRUGHUV 7UHDWPHQW ZLWK WRFLOL]XPDE
VKRXOGEHLQWHUUXSWHGGXULQJDVVHVVPHQWRIDSRWHQWLDOGHP\HOLQDWLRQHYHQWDQG
RQO\UHVXPHGLIWKHEHQHILWRIFRQWLQXLQJVWXG\GUXJLVIDYRUDEOH

+HPDWRORJLF$EQRUPDOLWLHVDQG%OHHGLQJ(YHQWV

'HFUHDVHV LQ QHXWURSKLO DQG SODWHOHW FRXQWV KDYH EHHQ REVHUYHG IROORZLQJ
WUHDWPHQW ZLWK 7&= LQ FRPELQDWLRQ ZLWK 07; ,Q DGGLWLRQ WKHUH PD\ EH DQ
LQFUHDVHGULVNRIQHXWURSHQLDLQSDWLHQWVZKRKDYHSUHYLRXVO\EHHQWUHDWHGZLWKD
71)DQWDJRQLVW

7KH ULVN PLWLJDWLRQ VWUDWHJLHV IRU QHXWURSHQLD DQG WKURPERF\WRSHQLD DUH
VXPPDUL]HGLQ7DEOHDQG7DEOHUHVSHFWLYHO\)RUSDWLHQWVZLWKFRQFRPLWDQW
PHGLFDWLRQVDVVRFLDWHGZLWKKHPDWRORJLFWR[LFLW\WKHUHGXFWLRQRULQWHUUXSWLRQRI
WKHVXVSHFWHGPHGLFDWLRQLVUHFRPPHQGHGSULRUWRPRGLI\LQJ7&=
7DEOH1HXWURSHQLD5LVN0LWLJDWLRQ
 
$1&FHOOVPP
$FWLRQ
!
0DLQWDLQGRVH
±
,QWHUUXSWWRFLOL]XPDEGRVLQJ
:KHQ$1&LQFUHDVHVWR!UHVXPHWRFLOL]XPDEDW
PJNJDQGLQFUHDVHWRPJNJPD[LPXPGRVH


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 19 of 33 
9HUVLRQ'$7( 
PJDVFOLQLFDOO\DSSURSULDWH

'LVFRQWLQXHWRFLOL]XPDE
$1& DEVROXWHQHXWURSKLOFRXQW

7DEOH7KURPERF\WRSHQLD5LVN0LWLJDWLRQ
 
3ODWHOHWFRXQW
FHOOVPP
$FWLRQ
!
0DLQWDLQGRVH
±
,QWHUUXSWWRFLOL]XPDEGRVLQJ
:KHQSODWHOHWFRXQWLQFUHDVHVWR!UHVXPH
WRFLOL]XPDEDWPJNJDQGLQFUHDVHWR
PJNJPD[LPXPGRVHPJDVFOLQLFDOO\DSSURSULDWH

'LVFRQWLQXHWRFLOL]XPDE


(OHYDWHG/LYHU(Q]\PHVDQG+HSDWLF(YHQWV

(OHYDWLRQVLQ$/7DQG$67KDYHEHHQREVHUYHGGXULQJWUHDWPHQWZLWKWKHVWXG\
PHGLFDWLRQV

7DEOH
 
/DE9DOXH
$FWLRQ
!WR[8/1
'RVHPRGLI\FRQFRPLWDQW'0$5'VLIDSSURSULDWH

)RUSHUVLVWHQWLQFUHDVHVLQWKLVUDQJHUHGXFHWRFLOL]XPDE
GRVHWRPJNJRULQWHUUXSWWRFLOL]XPDEXQWLO$/7$67
KDYHQRUPDOL]HG

5HVWDUWZLWKPJNJRUPJNJPD[LPXPGRVHPJ
DVFOLQLFDOO\DSSURSULDWH
!WR[8/1
FRQILUPHGE\UHSHDW
WHVWLQJ
,QWHUUXSWWRFLOL]XPDEGRVLQJXQWLO[8/1DQGIROORZ
UHFRPPHQGDWLRQVDERYHIRU!WR[8/1

)RUSHUVLVWHQWLQFUHDVHV![8/1GLVFRQWLQXHWRFLOL]XPDE
![8/1
'LVFRQWLQXHWRFLOL]XPDE

&DUGLRYDVFXODU(YHQWVDQG(OHYDWHG/LSLGV
 
3DWLHQWVZLWK5$KDYHDQLQFUHDVHGULVNIRUFDUGLRYDVFXODUGLVRUGHUVWKHUHIRUH
ULVNIDFWRUVIRUFDUGLRYDVFXODUGLVHDVHHJK\SHUWHQVLRQK\SHUOLSLGHPLDVKRXOG
EHPDQDJHGDVSDUWRIWKHLUVWDQGDUGRIFDUH6HHVHFWLRQRQ'UXJ,QWHUDFWLRQV
)RUSDWLHQWVZLWK/'/FKROHVWHUROPJG/LWLVVWURQJO\UHFRPPHQGHGWKDW
LQYHVWLJDWRUVDGYLVHWKHUDSHXWLFOLIHVW\OHFKDQJHVWKDWPD\LQFOXGHLQLWLDWLRQOLSLG


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 20 of 33 
9HUVLRQ'$7( 
ORZHULQJ DJHQWV /LSLGORZHULQJ DJHQWV VKRXOG DOVR EH FRQVLGHUHG IRU SDWLHQWV
ZLWK ORZHU /'/ FKROHVWHURO OHYHOV DV SDUW RI WKHLU WKHUDSHXWLF OLIHVW\OH FKDQJHV
GHSHQGLQJ RQ WKHLU RYHUDOO ULVN DV GHILQHG LQ 1&(3 $73,,, RU RWKHU QDWLRQDO
JXLGHOLQHV

0DOLJQDQFLHV
 
7KH LPSDFW RI LPPXQRVXSSUHVVLRQ RQ WKH GHYHORSPHQW RI PDOLJQDQFLHV LVQRW
NQRZQ KRZHYHU DQ LQFUHDVHG UDWH RI VRPH PDOLJQDQFLHV QRWDEO\ O\PSKRPD
KDVEHHQREVHUYHGLQ5$SDWLHQWV$OWKRXJKQRLPEDODQFHRIPDOLJQDQFLHVZDV
REVHUYHGLQFRQWUROOHGFOLQLFDOWULDOVRI7&=PDOLJQDQFLHVKDYHEHHQLGHQWLILHGDV
DFRQFHUQIRURWKHUELRORJLFV,WLVUHFRJQL]HGWKDWLGHQWLILFDWLRQRIVXFKHYHQWVLQ
7&=WUHDWHGSDWLHQWVPD\UHTXLUHDORQJHUSHULRGRIVXUYHLOODQFH7&=VKRXOGEH
GLVFRQWLQXHGLQSDWLHQWVZLWKPDOLJQDQFLHVZLWKWKHH[FHSWLRQRIORFDOEDVDORU
VTXDPRXV FHOO FDUFLQRPD RI WKH VNLQ WKDW LV FRPSOHWHO\ H[FLVHG ZLWK IUHH
PDUJLQV

+\SHUVHQVLWLYLW\RU$QDSK\OD[LV

$QLQIXVLRQGRVHUHDFWLRQLVGHILQHGDVDQDGYHUVHHYHQWRFFXUULQJGXULQJDQG
ZLWKLQKRXUVDIWHUWKHLQIXVLRQRUVXEFXWDQHRXVLQMHFWLRQRIWRFLOL]XPDE7KLV
PD\LQFOXGHK\SHUVHQVLWLYLW\UHDFWLRQVRUDQDSK\ODFWLFUHDFWLRQV

6LJQVRIDSRVVLEOHK\SHUVHQVLWLYLW\UHDFWLRQLQFOXGHEXWDUHQRWOLPLWHGWR
x IHYHUFKLOOVSUXULWXVXUWLFDULDDQJLRHGHPDDQGVNLQUDVK
x FDUGLRSXOPRQDU\ UHDFWLRQV LQFOXGLQJ FKHVW SDLQ G\VSQHD K\SRWHQVLRQ RU
K\SHUWHQVLRQ

+HDOWKFDUH SURIHVVLRQDOV DGPLQLVWHULQJ 7&= LQIXVLRQV VKRXOG EH WUDLQHG LQ WKH
DSSURSULDWH DGPLQLVWUDWLYH SURFHGXUHV EH DEOH WR UHFRJQL]H WKH V\PSWRPV
DVVRFLDWHGZLWKSRWHQWLDODQDSK\ODFWLFRUK\SHUVHQVLWLYLW\UHDFWLRQVDQGKDYHWKH
DSSURSULDWH PHGLFDWLRQ DYDLODEOH IRU LPPHGLDWH XVH LQ FDVH RI DQDSK\OD[LV RU
K\SHUVHQVLWLYLW\ UHDFWLRQ GXULQJ RU DIWHU DGPLQLVWUDWLRQ RI 7&=  +HDOWKFDUH
SURIHVVLRQDOV VKRXOG DOVR LQVWUXFW SDWLHQWV WR VHHN PHGLFDO DWWHQWLRQ LI WKH\
H[SHULHQFHV\PSWRPVRIDK\SHUVHQVLWLYLW\UHDFWLRQRXWVLGHRIWKHFOLQLF

,IDSDWLHQWKDVV\PSWRPVRIDQDSK\OD[LVRUVHULRXVK\SHUVHQVLWLYLW\RUUHTXLUHV
DQ LQWHUUXSWLRQ RI WKH VWXG\ GUXJ EHFDXVH RI V\PSWRPV RI DQDSK\OD[LV RU
K\SHUVHQVLWLYLW\ DGPLQLVWUDWLRQ RI 7&= PXVW EH GLVFRQWLQXHG SHUPDQHQWO\ DQG
WKHSDWLHQWVKRXOGEHZLWKGUDZQIURPWKHVWXG\7KHSDWLHQWVKRXOGEHWUHDWHG
DFFRUGLQJ WR WKH VWDQGDUG RI FDUH IRU PDQDJHPHQW RI WKH K\SHUVHQVLWLYLW\
UHDFWLRQ$EORRGVDPSOHIRUWKHSUHVHQFHRIDQWLWRFLOL]XPDEDQWLERGLHVVKRXOG
EHREWDLQHGDWWLPHRIHYHQWDQGDWOHDVWZHHNVDIWHUWKHODVWGRVH

ZHHNVIRUWKH5$LQGLFDWLRQ)RURWKHULQGLFDWLRQVFRQVXOWDWLRQZLWKWKHFOLQLFDO
SKDUPDFRORJ\JURXSZLOOEHUHTXLUHGWRDVVHVVKRZPDQ\ZHHNVDIWHUWKHODVW
GRVHWHVWLQJVKRXOGEHFRQGXFWHG



7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 21 of 33 
9HUVLRQ'$7( 
9LUDO5HDFWLYDWLRQ
7KRXJKUDUHO\UHSRUWHGZLWKLQWKH7&=SURJUDPGXHWRH[FOXVLRQFULWHULDDWVWXG\
HQWU\UHDFWLYDWLRQRIYLUDODQGRWKHUVHULRXVLQIHFWLRQVHJ(%9RU7%KDVEHHQ
REVHUYHGZLWKELRORJLFWKHUDSLHVIRU5$LQFOXGLQJ7&=

'UXJ,QWHUDFWLRQ
x 7KHIRUPDWLRQRI&<3HQ]\PHVPD\EHVXSSUHVVHGE\LQFUHDVHG
OHYHOVRIF\WRNLQHVHJ,/GXULQJFKURQLFLQIODPPDWLRQ7KHUHIRUHLW
LVH[SHFWHGWKDWIRUPROHFXOHVWKDWDQWDJRQL]HF\WRNLQHDFWLYLW\VXFK
DV 7&= WKH IRUPDWLRQ RI &<3 HQ]\PHV FRXOG EH QRUPDOL]HG
:KHQ VWDUWLQJ RU VWRSSLQJ WKHUDS\ ZLWK 7&= SDWLHQWV WDNLQJ
PHGLFDWLRQVZKLFKDUHLQGLYLGXDOO\GRVHDGMXVWHGDQGPHWDEROL]HGYLD
&<3 $ $ RU & HJ DWRUYDVWDWLQ FDOFLXP FKDQQHO
EORFNHUV
WKHRSK\OOLQH
ZDUIDULQ
SKHQ\WRLQ
FLFORVSRULQ
RU
EHQ]RGLD]HSLQHV VKRXOG EH PRQLWRUHG DV GRVHV PD\ QHHG WR EH
DGMXVWHGWRPDLQWDLQWKHLUWKHUDSHXWLFHIIHFW*LYHQLWVORQJHOLPLQDWLRQ
KDOIOLIH W WKH HIIHFW RI WRFLOL]XPDE RQ &<3 HQ]\PH DFWLYLW\
PD\SHUVLVWIRUUHDFWLRQ
x $/7RU$67YDOXH!;8/1RUSHUVLVWHQWHOHYDWLRQ!;8/1
x 3ODWHOHWFRXQWFHOOVPP
x $1&FHOOVPP


&5,7(5,$)2568%-(&7',6&217,18$7,21

6XEMHFWVZKRPHHWWKHIROORZLQJFULWHULDVKRXOGEHGLVFRQWLQXHGIURPWKHVWXG\


7RFLOL]XPDE6SHFLILF&ULWHULD

x 6HYHUHRUOLIHWKUHDWHQLQJDQDSK\OD[LVRUK\SHUVHQVLWLYLW\
6XEMHFWVZKRDUHFDUULHUVRIKHSDWLWLV%DWWKHWLPHRIGLVFRQWLQXDWLRQIURPVWXG\
WUHDWPHQWZLOOFRQWLQXHWREHIROORZHGIRUFOLQLFDODQGODERUDWRU\VLJQVRIDFWLYH
+%9LQIHFWLRQDQGIRUVLJQVRIKHSDWLWLV


*HQHUDO&ULWHULD

x ,QDELOLW\RIVXEMHFWWRFRPSO\ZLWKVWXG\UHTXLUHPHQWV
'HWHUPLQDWLRQE\WKHLQYHVWLJDWRUWKDWLWLVQRORQJHUVDIHIRUWKHVXEMHFWWR
FRQWLQXHWKHUDS\VHYHUDOZHHNVDIWHUVWRSSLQJ
WKHUDS\


&5,7(5,$)25678'<',6&217,18$7,21
$VVWDWHGDERYH


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 22 of 33 
9HUVLRQ'$7( 

&/,1,&$/$1'/$%25$725<(9$/8$7,216
3URFHGXUH
3UH
7UHDWPHQW
6FUHHQLQJ
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
%DVHOLQH
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
6DIHW\
)ROORZ
XS
9LVLW7LPH
:LQGRZ



ZHHNV

ZHHNV

ZHHNV

ZHHNV

ZHHNV

ZHHNV

(OLJLELOLW\
$VVHVVPHQWV









,QIRUPHG&RQVHQW
;








,QFOXVLRQ([FOXVLRQ
&ULWHULD
;
;







0HGLFDO+LVWRU\
;








6DIHW\
$VVHVVPHQWV









&KHVW;UD\3$
ODWHUDO
;








33'VNLQWHVWLQJ
;








4XDQWLIHURQLI
33'RUSDWLHQW
IURPHQGHPLFDUHD
;








3K\VLFDO
([DPLQDWLRQ
;








7DUJHWHG3K\VLFDO
([DPLQDWLRQ

;
;

;
;

;

9LWDO6LJQV
;
;
;
;
;
;
;
;

$VVHVVPHQWRI
6LJQVDQG
6\PSWRPV

;
;

;


;

$GYHUVH(YHQWV
$VVHVVPHQW

;
;
;
;
;
;
;
;
&%&DQG&KHP
3DQHO7HVWV
;
;

;
;
;
;
;

/LSLG3DQHO

;

;



;

+,9+HSDWLWLV%
DQG&6HURORJLHV
;








5KHXPDWRLG)DFWRU
DQG&&3
;








KV&53
;
;


;


;

(65
;
;
;

;
;

;

8ULQH3UHJQDQF\
7HVW
;
;
;
;
;
;
;
;

(IILFDF\
$VVHVVPHQWV











7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 23 of 33 
9HUVLRQ'$7( 
3URFHGXUH
3UH
7UHDWPHQW
6FUHHQLQJ
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
%DVHOLQH
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
'XULQJ
7UHDWPHQW
9LVLW
ZHHN
9LVLW
6DIHW\
)ROORZ
XS
-RLQW$VVHVVPHQW
;
;
;

;
;

;

0'*OREDO
;
;
;

;
;

;

3DWLHQW*OREDO
;
;
;

;
;

;

&'$,
;
;
;

;
;

;

'$6(65
;
;
;

;
;

;

+$4',DQGRWKHU
TXHVWLRQQDLUHV
;
;


;


;

,QIXVLRQRI7&=

;
;
;
;
;
;
;

6HUXPEORRGIRU
ELRPDUNHUWHVWLQJ
;
;


;


;

8OWUDVRXQGMRLQW
6FRULQJ
;
;
;

;
;

;

8OWUDVRXQGMRLQW
5HUHDG

;
;

;
;

;


,IDFKHVW;UD\RU&7VFDQRIFKHVWZDVGRQHZLWKLQWKHSDVWPRQWKVWKHUHLVQR
QHHGWRUHSHDW

33'VNLQWHVWLQJRU4XDQWLIHURQGRHVQRWKDYHWREHGRQHLIHLWKHUSURFHGXUHZDV
GRQHZLWKLQWKHSDVWPRQWKV

&%&DQG&KHPSDQHOODERUDWRU\WHVWVGRQRWKDYHWREHGRQHLIWKH\ZHUHGRQH
ZLWKLQWKHSDVWZHHNV$GGLWLRQDOWHVWLQJPD\EHFRQGXFWHGIRUVDIHW\UHDVRQV

+HSDWLWLV%DQG&6HURORJLHVGRQRWKDYHWREHGRQHLIWKH\ZHUHGRQHZLWKLQWKHSDVW
PRQWKV

5KHXPDWRLG)DFWRUDQG&&3WHVWVGRQRWKDYHWREHGRQHDWVFUHHQLQJLIWKH\ZHUH
GRQHSUHYLRXVO\

%LRPDUNHUWHVWLQJPD\EHSHUIRUPHGDWHLWKHUVFUHHQLQJDQGRUEDVHOLQH3DWLHQWV
KDYHWKHULJKWWRUHIXVHELRPDUNHUWHVWLQJ

6WXG\SURFHGXUHVPD\EHUHSHDWHGSHU3,GLVFUHWLRQ,WHPVWRDERYHLH)RU
VHURQHJDWLYH5$SDWLHQWV3,PD\UHSHDW5)DQG&&3WRHQVXUHWKH\GLGQRWVHUR
FRQYHUW&KHVW[UD\PD\EHUHSHDWHGLIDQDEQRUPDOLW\UHTXLUHVIXUWKHUDVVHVVPHQW


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 24 of 33 
9HUVLRQ'$7( 

 3UH7UHDWPHQW(YDOXDWLRQV

8QOHVVRWKHUZLVHVSHFLILHGWKHIROORZLQJHYDOXDWLRQVPXVWEHSHUIRUPHGZLWKLQ
IRXUZHHNVSULRUWRWKHGDWHRIHDFKSDWLHQW
VLQLWLDOWUHDWPHQWZLWK7RFLOL]XPDE

x 3UHJQDQF\WHVWVHUXPRUXULQHIRUZRPHQRIFKLOGEHDULQJSRWHQWLDO
x 0HGLFDOKLVWRU\DQGGRFXPHQWDWLRQRIWKHUDWLRQDOHIRUWUHDWPHQWRIWKH
SDWLHQW
VGLVHDVHZLWK7RFLOL]XPDE
x 3K\VLFDOH[DPLQDWLRQLQFOXGLQJYLWDOVLJQVEORRGSUHVVXUHSHUIRUPDQFH
VWDWXVDQGWXPRUDVVHVVPHQW
x +HPDWRORJ\FRPSOHWHEORRGFRXQW&%&ZLWKGLIIHUHQWLDODQGSODWHOHWFRXQW
x 6HUXP&KHPLVWULHV7RWDOELOLUXELQ6*27$67DQG6*37$/7
x /LSLG3DQHO

 (YDOXDWLRQV'XULQJ7UHDWPHQW

/DERUDWRU\HYDOXDWLRQVIRUVDIHW\
x 1HXWURSKLOVVKRXOGEHPRQLWRUHGHYHU\WRZHHNV
x 3ODWHOHWVVKRXOGEHPRQLWRUHGHYHUWRZHHNV
x $/7DQG$67OHYHOVVKRXOGEHPRQLWRUHGHYHU\WRZHHNV
x $VVHVVPHQWRIOLSLGSDUDPHWHUVVKRXOGEHSHUIRUPHGDSSUR[LPDWHO\WR
ZHHNVIROORZLQJLQLWLDWLRQRI7&=WKHUDS\WKHQDWDSSUR[LPDWHO\PRQWK
LQWHUYDOV

 3RVW7UHDWPHQW(YDOXDWLRQV

(DFKSDWLHQWZLOOUHFHLYHDWHOHSKRQHFDOORUZHZLOOH[WUDFWLQIRUPDWLRQIURP
SULPDU\UKHXPDWRORJLVW¶VYLVLWDSSUR[LPDWHO\WRPRQWKVDIWHUWKHVWXG\WR
HYDOXDWHIRUDQ\DGYHUVHHYHQWVRUVHULRXVDGYHUVHHYHQWV


 5(3257,1*2)$'9(56((9(176

 $GYHUVH(YHQWDQG5HSRUWLQJ'HILQLWLRQV

,QWKHHYHQWRIDQDGYHUVHHYHQWWKHILUVWFRQFHUQZLOOEHIRUWKHVDIHW\RIWKH
VXEMHFW,QYHVWLJDWRUVDUHUHTXLUHGWRUHSRUWWR*HQHQWHFK'UXJ6DIHW\DQ\
VHULRXVDGYHUVHHYHQWZKHWKHUH[SHFWHGRUXQH[SHFWHGIRUZKLFKWKHUHLVD
UHDVRQDEOHSRVVLELOLW\WKHH[SHULHQFHPD\KDYHEHHQFDXVHGE\7RFLOL]XPDE

7KH6SRQVRU,QYHVWLJDWRUIXUWKHUDJUHHVWRIRUZDUGUHSRUWVWR*HQHQWHFKRI
VHULRXVDGYHUVHHYHQWVUHJDUGOHVVRIUHODWLRQVKLSZLWKWKHXVHRIWKH
,QYHVWLJDWLRQDOPHGLFLQDOSURGXFW



7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 25 of 33 
9HUVLRQ'$7( 
$OOHYHQWVPHHWLQJWKHVHFULWHULDZLOOEHUHSRUWHGIRUWKHWLPHSHULRGEHJLQQLQJ
ZLWKDQ\DPRXQWRIH[SRVXUHWR7RFLOL]XPDEWKURXJKWKHSURWRFROGHILQHGIROORZ
XSSHULRG6HULRXVFULWHULDGHILQLWLRQVDQGJXLGDQFHIRUUHSRUWLQJIROORZ

$QDGYHUVHHYHQW$(LVDQ\XQWRZDUGPHGLFDORFFXUUHQFHLQDVXEMHFW
SDUWLFLSDWLQJLQDQLQYHVWLJDWLRQDOWULDORUSURWRFROUHJDUGOHVVRIFDXVDOLW\
DVVHVVPHQW$QDGYHUVHHYHQWFDQEHDQXQIDYRUDEOHDQGXQLQWHQGHGVLJQ
LQFOXGLQJDQDEQRUPDOODERUDWRU\ILQGLQJV\PSWRPV\QGURPHRUGLVHDVH
DVVRFLDWHGZLWKRURFFXUULQJGXULQJWKHXVHRIDQLQYHVWLJDWLRQDOSURGXFWZKHWKHU
RUQRWFRQVLGHUHGUHODWHGWRWKHLQYHVWLJDWLRQDOSURGXFW

6HULRXVDGYHUVHHYHQWV6$(DUHDGYHUVHHYHQWVRFFXUULQJDWDQ\GRVHZKLFK
PHHWRQHRUPRUHRIWKHIROORZLQJVHULRXVFULWHULD

x 5HVXOWVLQGHDWKLHWKH$(FDXVHGRUOHDGWRGHDWK

x ,VOLIHWKUHDWHQLQJLHWKH$(SODFHGWKHVXEMHFWDWLPPHGLDWHULVNRIGHDWK
LWGRHVQRWDSSO\WRDQ$(ZKLFKK\SRWKHWLFDOO\PLJKWKDYHFDXVHGWKHGHDWK
LILWZHUHPRUHVHYHUH

x 5HTXLUHVRUSURORQJVLQSDWLHQWKRVSLWDOL]DWLRQLHWKH$(LQSDWLHQW
KRVSLWDOL]DWLRQRUSURORQJHGDKRVSLWDOL]DWLRQEH\RQGWKHH[SHFWHGOHQJWKRI
VWD\KRVSLWDOL]DWLRQVIRUHOHFWLYHPHGLFDOVXUJLFDOSURFHGXUHVVFKHGXOHG
WUHDWPHQWVRUURXWLQHFKHFNXSVDUHQRW6$(VE\WKLVFULWHULRQ

x ,VGLVDEOLQJLHWKH$(UHVXOWHGLQDVXEVWDQWLDOGLVUXSWLRQRIWKHVXEMHFW¶V
DELOLW\WRFDUU\RXWQRUPDOOLIHIXQFWLRQV

x ,VDFRQJHQLWDODQRPDO\ELUWKGHIHFWLHDQDGYHUVHRXWFRPHLQDFKLOGRU
IHWXVRIDVXEMHFWH[SRVHGWRWKHWULDOGUXJSULRUWRFRQFHSWLRQRUGXULQJ
SUHJQDQF\

x ,WGRHVQRWPHHWDQ\RIWKHDERYHVHULRXVFULWHULDEXWPD\MHRSDUGL]HWKH
VXEMHFWDQGPD\UHTXLUHPHGLFDORUVXUJLFDOLQWHUYHQWLRQWRSUHYHQWRQH
RIWKHRXWFRPHVOLVWHGDERYH

6$(VLQFOXGHDQ\VLJQV\PSWRPRUPHGLFDOFRQGLWLRQWKDWPHHWVDQ\RIWKH
DERYHFULWHULDDQGHPHUJHVGXULQJ7RFLOL]XPDEWUHDWPHQWRUGXULQJDSRVW
WUHDWPHQWIROORZXSSHULRGWKDWZDVQRWSUHVHQWDWWKHVWDUWRIWUHDWPHQWDQG
LVQRWDFKURQLFFRQGLWLRQWKDWLVSDUWRIWKHSDWLHQW¶VPHGLFDOKLVWRU\25ZDV
SUHVHQWDWWKHVWDUWRIWUHDWPHQWRUDVSDUWRIWKHSDWLHQW¶VPHGLFDOKLVWRU\EXW
ZRUVHQHGLQVHYHULW\DQGRUIUHTXHQF\GXULQJWKHUDS\

([SHFWHGDGYHUVHHYHQWVDUHWKRVHDGYHUVHHYHQWVWKDWDUHOLVWHGRU
FKDUDFWHUL]HGLQWKHFXUUHQW,QYHVWLJDWRU%URFKXUH

8QH[SHFWHGDGYHUVHHYHQWVDUHWKRVHQRWOLVWHGLQWKHFXUUHQW,QYHVWLJDWRU
%URFKXUHRUQRWLGHQWLILHG7KLVLQFOXGHVDGYHUVHHYHQWVIRUZKLFKWKHVSHFLILFLW\


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 26 of 33 
9HUVLRQ'$7( 
RUVHYHULW\LVQRWFRQVLVWHQWZLWKWKHGHVFULSWLRQLQWKH,QYHVWLJDWRU%URFKXUH)RU
H[DPSOHXQGHUWKLVGHILQLWLRQKHSDWLFQHFURVLVZRXOGEHXQH[SHFWHGLIWKH
,QYHVWLJDWRU%URFKXUHRQO\UHIHUUHGWRHOHYDWHGKHSDWLFHQ]\PHVRUKHSDWLWLV

 5HSRUWLQJRI6HULRXV$GYHUVH(YHQWV$VVRFLDWHGZLWK7RFLOL]XPDE

$OOVHULRXVDGYHUVHHYHQWV6$(VWKLVDSSOLHVWRERWKH[SHFWHGDQGXQH[SHFWHG
HYHQWVVKRXOGEHUHFRUGHGRQD0HG:DWFK$)RUPDQGID[HGWR

*HQHQWHFK'UXJ6DIHW\
7HO

)D[ RU

7KLVPXVWEHUHSRUWHGWR*HQHQWHFKZLWKLQKRXUV

3OHDVHXVHWKHVDIHW\UHSRUWLQJID[FRYHUVKHHWDWWDFKHGWRWKLVGRFXPHQWIRU
\RXUID[WUDQVPLVVLRQ

0HG:DWFK$5HSRUWLQJ*XLGHOLQHV

,QDGGLWLRQWRFRPSOHWLQJDSSURSULDWHSDWLHQWGHPRJUDSKLFDQGVXVSHFW
PHGLFDWLRQLQIRUPDWLRQWKHUHSRUWVKRXOGLQFOXGHWKHIROORZLQJLQIRUPDWLRQZLWKLQ
WKH(YHQW'HVFULSWLRQVHFWLRQRIWKH0HG:DWFK$IRUP

x 7UHDWPHQWUHJLPHQGRVLQJIUHTXHQF\FRPELQDWLRQWKHUDS\
x 3URWRFROGHVFULSWLRQDQGQXPEHULIDVVLJQHG
x 'HVFULSWLRQRIHYHQWVHYHULW\WUHDWPHQWDQGRXWFRPHLINQRZQ
x 6XSSRUWLYHODERUDWRU\UHVXOWVDQGGLDJQRVWLFV
x ,QYHVWLJDWRU¶VDVVHVVPHQWRIWKHUHODWLRQVKLSRIWKHDGYHUVHHYHQWWRHDFK
LQYHVWLJDWLRQDOSURGXFWDQGVXVSHFWPHGLFDWLRQ

)ROORZXSLQIRUPDWLRQ

$GGLWLRQDOLQIRUPDWLRQPD\EHDGGHGWRDSUHYLRXVO\VXEPLWWHGUHSRUWE\DQ\RI
WKHIROORZLQJPHWKRGV

x $GGLQJWRWKHRULJLQDO0HG:DWFK$UHSRUWDQGVXEPLWWLQJLWDVIROORZXS
x $GGLQJVXSSOHPHQWDOVXPPDU\LQIRUPDWLRQDQGVXEPLWWLQJLWDVIROORZXSZLWK
WKHRULJLQDO0HG:DWFK$IRUP
x 6XPPDUL]LQJQHZLQIRUPDWLRQDQGID[LQJLWZLWKDFRYHUOHWWHULQFOXGLQJ
VXEMHFWLGHQWLILHUVLH'2%LQLWLDOVXEMHFWQXPEHUSURWRFROGHVFULSWLRQ
DQGQXPEHULIDVVLJQHGVXVSHFWGUXJEULHIDGYHUVHHYHQWGHVFULSWLRQDQG
QRWDWLRQWKDWDGGLWLRQDORUIROORZXSLQIRUPDWLRQLVEHLQJVXEPLWWHG7KH
SDWLHQWLGHQWLILHUVDUHLPSRUWDQWVRWKDWWKHQHZLQIRUPDWLRQLVDGGHGWRWKH
FRUUHFWLQLWLDOUHSRUW

2FFDVLRQDOO\*HQHQWHFKPD\FRQWDFWWKHUHSRUWHUIRUDGGLWLRQDOLQIRUPDWLRQ
FODULILFDWLRQRUFXUUHQWVWDWXVRIWKHVXEMHFWIRUZKRPDQGDGYHUVHHYHQWZDV


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 27 of 33 
9HUVLRQ'$7( 
UHSRUWHG)RUTXHVWLRQVUHJDUGLQJ6$(UHSRUWLQJ\RXPD\FRQWDFWWKH
*HQHQWHFK'UXJ6DIHW\UHSUHVHQWDWLYHQRWHGDERYH

6WXG\'UXJ5HODWLRQVKLS

7KHLQYHVWLJDWRUZLOOGHWHUPLQHZKLFKHYHQWVDUHDVVRFLDWHGZLWKWKHXVHRIWKH
VWXG\GUXJV)RUUHSRUWLQJSXUSRVHVDQ$(VKRXOGEHUHJDUGHGDVSRVVLEO\
UHODWHGWRWKHXVHRIWKHLQYHVWLJDWLRQDOSURGXFWLIWKHLQYHVWLJDWRUEHOLHYHV

x 7KHUHLVDFOLQLFDOO\SODXVLEOHWLPHVHTXHQFHEHWZHHQRQVHWRIWKH$(DQG
7RFLOL]XPDEDGPLQLVWUDWLRQDQGRU
x 7KHUHLVDELRORJLFDOO\SODXVLEOHPHFKDQLVPIRU7RFLOL]XPDEFDXVLQJRU
FRQWULEXWLQJWRWKH$(DQG
x 7KH$(FDQQRWEHDWWULEXWHGVROHO\WRFRQFXUUHQWXQGHUO\LQJLOOQHVVRWKHU
GUXJVRUSURFHGXUHV

3UHJQDQF\

)HPDOHSDWLHQWVVKRXOGXVHDUHOLDEOHPHDQVRIFRQWUDFHSWLRQGXULQJWKHVWXG\
DQGIRUDPLQLPXPRIPRQWKVDIWHUWKHODVWGRVHRIVWXG\PHGLFDWLRQ$IHPDOH
SDWLHQWPXVWEHLQVWUXFWHGWRVWRSWDNLQJWKHVWXG\PHGLFDWLRQDQGLPPHGLDWHO\
LQIRUPWKHLQYHVWLJDWRULIVKHEHFRPHVSUHJQDQWGXULQJWKHVWXG\7KH
LQYHVWLJDWRUVKRXOGUHSRUWDOOSUHJQDQFLHVZLWKLQKRXUVWRWKH*HQHQWHFK'UXJ
6DIHW\XVLQJWKH&OLQLFDO7ULDO3UHJQDQF\5HSRUWLQJ)RUP?SURYLGHGE\
*HQHQWHFK'UXJ6DIHW\7KHLQYHVWLJDWRUVKRXOGFRXQVHOWKHSDWLHQWGLVFXVVWKH
ULVNVRIFRQWLQXLQJZLWKWKHSUHJQDQF\DQGWKHSRVVLEOHHIIHFWVRQWKHIHWXV
0RQLWRULQJRIWKHSDWLHQWVKRXOGFRQWLQXHXQWLOWKHFRQFOXVLRQRIWKHSUHJQDQF\
3UHJQDQFLHVRFFXUULQJXSWRPRQWKVDIWHUWKHFRPSOHWLRQRIWKHVWXG\
PHGLFDWLRQPXVWDOVREHUHSRUWHGWRWKHLQYHVWLJDWRU$ERUWLRQZKHWKHU
WKHUDSHXWLFRUVSRQWDQHRXVVKRXOGDOZD\VEHFODVVLILHGDVVHULRXVDV
*HQHQWHFKFRQVLGHUVWKHVHPHGLFDOO\VLJQLILFDQWUHFRUGHGRQWKHDSSURSULDWH
H&5)DQGH[SHGLWLRXVO\UHSRUWHGWRWKH6SRQVRURULWVGHVLJQHH

 $FWHPUD(YHQWVRI6SHFLDO,QWHUHVW

$GYHUVHHYHQWVRIVSHFLDOLQWHUHVWQRQVHULRXVDQGVHULRXVDUHUHTXLUHGWREH
UHSRUWHGE\WKH,QYHVWLJDWRUWR*HQHQWHFK'UXJ6DIHW\ZLWKLQZRUNLQJGD\DIWHU
OHDUQLQJRIWKHHYHQWVHH6HFWLRQIRUUHSRUWLQJLQVWUXFWLRQV1RQVHULRXV
DQGVHULRXV$(VRIVSHFLDOLQWHUHVWIRUWKLVVWXG\LQFOXGHWKHIROORZLQJ

x
,QIHFWLRQVLQFOXGLQJRSSRUWXQLVWLFLQIHFWLRQVDQGQRQVHULRXVLQIHFWLRQVDV
GHILQHGE\WKRVHWUHDWHGZLWK,&DQWLLQIHFWLYHV
x
0\RFDUGLDOLQIDUFWLRQDFXWHFRURQDU\V\QGURPH
x
*,SHUIRUDWLRQDQGUHODWHGHYHQWV
x
0DOLJQDQFLHV
x
$QDSK\OD[LV+\SHUVHQVLWLYLW\UHDFWLRQV
x
'HP\HOLQDWLQJGLVRUGHUV


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 28 of 33 
9HUVLRQ'$7( 
x
6WURNH
x
%OHHGLQJHYHQWV
x
+HSDWLFHYHQWV

*XLGHGTXHVWLRQQDLUHVKDYHEHHQSUHSDUHGIRUWKH$(VRIVSHFLDOLQWHUHVW7KH
VDPHJXLGHGTXHVWLRQQDLUHVDUHXWLOL]HGIRU6HULRXV,QIHFWLRQVDQGRSSRUWXQLVWLF
LQIHFWLRQVWKHUHIRUHWKHUHDUHJXLGHGTXHVWLRQQDLUHVDQGFDWHJRULHVRI$(V
RIVSHFLDOLQWHUHVW

7KHQRWLILFDWLRQRI$(VRIVSHFLDOLQWHUHVWLQFOXGLQJQRQVHULRXVHYHQWVRI
VSHFLDOLQWHUHVWZLOOIROORZWKHHVWDEOLVKHGSURFHGXUHVIRU$(VDQG6$(VLQWKH
VWXG\LHGRFXPHQWHGDQGUHSRUWHGWR*HQHQWHFK'UXJ6DIHW\RULWVGHVLJQHH
ZLWKLQKRXUV*XLGHGTXHVWLRQQDLUHVKDYHEHHQSUHSDUHGIRUWKH$(VRI
VSHFLDOLQWHUHVWDQGZLOOEHVHQWWRWKHLQYHVWLJDWRUVWRREWDLQPRUHGHWDLOHG
LQIRUPDWLRQDVQHFHVVDU\7KHGRFXPHQWDWLRQDQGUHSRUWLQJUHTXLUHPHQWVIRU
WKRVH$(VRIVSHFLDOLQWHUHVWZLOOEHIXUWKHUGHVFULEHGLQDVHSDUDWHGRFXPHQW
$FWHPUD(YHQWVRI6SHFLDO,QWHUHVW*XLGDQFH'RFXPHQW

 (9$/8$7,212)5(63216(
3ULPDU\2XWFRPH0HDVXUHFKDQJHLQ3'86
6HFRQGDU\2XWFRPH0HDVXUHFKDQJHLQ%0RGHJUH\VFDOHV\QRYLDO
K\SHUWURSK\ 

 67$7,67,&$/&216,'(5$7,216

 'HWHUPLQDWLRQRI6DPSOH6L]H
 
3ULPDU\$LP

:HSODQWRHQUROOVXEMHFWV:HZLOOQRWLQFOXGHSDWLHQWVLQWRWKHDQDO\VHVZKR
KDGGLIIHUHQWXOWUDVRQRJUDSKHUVDWEDVHOLQHDQGPRQWKYLVLWVSDWLHQWV
SRWHQWLDOO\H[FOXGHGZLWKFKDQJHLQXOWUDVRQRJUDSKHUIURP%HQ$UW]LWR
5DQJDQDWKDW8&/$VLWH:HDVVXPHDPLVVHGYLVLWGURSRXWUDWHDW
PRQWKVDQGDGURSRXWUDWHDWZHHNVUHVXOWLQJLQDQH[SHFWHG
HYDOXDEOHVXEMHFWVDWIRUWKHZHHNDQDO\VHVDQGIRUWKHZHHNDQDO\VHV
)RUWKHSULPDU\DLPZHZLOOKDYHSRZHUWRGHWHFWFRUUHODWLRQEHWZHHQ
3'86DWPRQWKDQGFKDQJHLQ'$6(65DWPRQWKVRIDWOHDVW
DVVXPLQJDWHVWIRUWKHFRUUHODWLRQFRHIILFLHQWZLWKDWZRVLGHGVLJQLILFDQFH
OHYHO.XPHHWDOREVHUYHGDFRUUHODWLRQEHWZHHQZHHN3'86DQGZHHN
FKDQJHLQ'$6LQ5$SDWLHQWVWUHDWHGZLWKPJRI7RFLOL]XPDERI

)RUWKHH[SORUDWRU\DLPZHH[SHFWVXEMHFWVWRKDYHFRPSOHWHGDWDLQWKH
GRVHHVFDODWLRQDUP7KHPLQLPDOO\GHWHFWDEOHFRUUHODWLRQZLWKSRZHU
OHYHORIVLJQLILFDQFHLVZKLFKLVVPDOOHUWKDQWKHFRUUHODWLRQREVHUYHGLQ
.XPHHWDODVGHVFULEHGSUHYLRXVO\

3ODQQHG(IILFDF\(YDOXDWLRQV
 


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 29 of 33 
9HUVLRQ'$7( 
3ULPDU\(IILFDF\9DULDEOHV

7KHSULPDU\DQDO\VLVZLOOEHDVLQJOHSUHGLFWRUOLQHDUUHJUHVVLRQPRGHOZLWK
FKDQJHLQ'$6IURPEDVHOLQHWRZHHNVDVWKHRXWFRPHDQGFKDQJHLQ
3'86VFRUHVIURPEDVHOLQHWRZHHNVDVWKHSUHGLFWRU$GGLWLRQDODQDO\VHVZLOO
DGGFRYDULDWHVWRWKHOLQHDUUHJUHVVLRQPRGHOVXFKDVGHPRJUDSKLFPHDVXUHV
DJHVH[

([SORUDWRU\$QDO\VHV

([SORUDWRU\$QDO\VHV:HZLOOFRQVWUXFWDPL[HGHIIHFWVPRGHOVXVLQJ'$6
VFRUHVRYHUWLPHDVWKHRXWFRPHDQG3'86RYHUWLPHDVWKHSULPDU\SUHGLFWRU
:HZLOODVVHVVZKHWKHUVSHFLILFGHPRJUDSKLFRUFOLQLFDOPHDVXUHVDUHVLJQLILFDQW
LQWKHFRQWH[WRIWKHPRGHO

([S$LP7KHDQDO\VLVZLOOEHDVLQJOHSUHGLFWRUOLQHDUUHJUHVVLRQPRGHOZLWK
FKDQJHLQ'$6IURPZHHNVWRZHHNVDVWKHRXWFRPHDQGFKDQJHLQ
3'86VFRUHVIURPZHHNVWRZHHNVDVWKHSUHGLFWRU$GGLWLRQDODQDO\VHV
ZLOODGGFRYDULDWHVWRWKHOLQHDUUHJUHVVLRQPRGHOVVXFKDVEDVHOLQH'$6DQG
GHPRJUDSKLFPHDVXUHV:HZLOODOVRH[DPLQHWKHFRUUHODWLRQRIWKHFKDQJHV
IURPZHHNWRZHHNLQERWK3'86DQG'$6DQGWKHFRUUHODWLRQEHWZHHQ
FKDQJHLQ3'86EDVHOLQHWRZHHNYVFKDQJHLQ'$6IURPEDVHOLQHWR
ZHHNV

([S$LP:HZLOOFRQVWUXFWDORJLVWLFUHJUHVVLRQPRGHOWRHYDOXDWHWKH
UHODWLRQVKLSRIZHHN3'86VFRUHVZLWKWKHRXWFRPHRIORZGLVHDVHDFWLYLW\
'$6DWZHHNV:HZLOOFRQVWUXFWDQ52&FXUYHDQGFRPSXWHWKH
DUHDXQGHUWKHFXUYHWRHVWLPDWHWKHSUHGLFWLYHDELOLW\RIHDUO\XOWUDVRXQGVFRUHV
IRUSUHGLFWLRQRIDFKLHYLQJORZGLVHDVHDFWLYLW\1H[WZHZLOOGHILQHWKHRSWLPDO
FXWSRLQWIRUWKHZHHN3'86VFRUHDVWKHYDOXHWKDWPD[LPL]HVWKH<RXGHQ
LQGH[WKHVXPRIWKHVHQVLWLYLW\DQGVSHFLILFLW\IRUHDFKFXWSRLQWIRUSUHGLFWLRQRI
DFKLHYHPHQWRIORZGLVHDVHDFWLYLW\6LPLODUO\ZHZLOOXVHORJLVWLFUHJUHVVLRQWR
HYDOXDWHWKHUHODWLRQVKLSEHWZHHQWKH3'86VFRUHVDWZHHNVDQGWKH
RXWFRPHRIORZGLVHDVHDFWLYLW\$GGLWLRQDOO\ZHZLOOHYDOXDWHWKHFRUUHODWLRQRI
WKHFKDQJHLQ3'86RYHUWKHILUVWZHHNVZLWKWKHFKDQJHLQ'$6RYHUWKHILUVW
ZHHNV

([S$LP7KHXQLWRIREVHUYDWLRQIRUWKLVDQDO\VLVZLOOEHMRLQWVUDWKHUWKDQ
VXEMHFWV:HZLOOXVHYDULRXVPHWKRGVWRDVVHVVWKHOHYHORIDJUHHPHQWEHWZHHQ
3'86DQGFOLQLFDOMRLQWDVVHVVPHQW:HZLOOXVH.DSSDVWDWLVWLFVWRFRPSDUHWKH
UHODWLRQVKLSEHWZHHQ3'86DQGH[DPIRUHDFKMRLQWVHSDUDWHO\$QDGGLWLRQDO
DQDO\VLVZLOOVXPWKH3'86VFRUHVDFURVVWKHVHWRIMRLQWVDQGUHODWHWKLVWRWKH
FRPSDUDEOHSK\VLFLDQMRLQWVFRUHVE\DVVHVVLQJ6SHDUPDQFRUUHODWLRQVDQG
%ODQG$OWPDQSORWVDWHDFKWLPHSRLQW)LQDOO\ZHZLOOXVHUHSHDWHGPHDVXUHV
PRGHOVDQGUHSHDWHGPHDVXUHV%ODQG$OWPDQSORWVWRH[DPLQHWKHUHODWLRQVKLSV
LQFOXGLQJDOOWLPHSRLQWVVLPXOWDQHRXVO\



7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 30 of 33 
9HUVLRQ'$7( 
,QDGGLWLRQZHZLOOXWLOL]HPL[HGHIIHFWVOLQHDUUHJUHVVLRQPRGHOVWRHYDOXDWHWKH
UHODWLRQVKLSEHWZHHQWKHF\WRNLQHVFKHPRNLQHVOLSLGVDQG3'86ORQJLWXGLQDOO\
DQGFURVVVHFWLRQDOO\


 5(7(17,212)5(&25'6

:HZLOOUHWDLQDOOGRFXPHQWDWLRQRIDGYHUVHHYHQWVUHFRUGVRIWULDOGUXJUHFHLSWDQG
GLVSHQVDWLRQDQGDOO,5%FRUUHVSRQGHQFHIRUDWOHDVW\HDUVDIWHUWKHLQYHVWLJDWLRQLV
FRPSOHWHG


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 31 of 33 
9HUVLRQ'$7( 

5()(5(1&(6%,%/,2*5$3+<


(PHU\3.H\VWRQH(7RQ\+3&DQWDJUHO$YDQ9ROOHQKRYHQ5
6DQFKH]$$OHFRFN(/HH-.UHPHU-,/UHFHSWRULQKLELWLRQZLWK
WRFLOL]XPDELPSURYHVWUHDWPHQWRXWFRPHVLQSDWLHQWVZLWK
UKHXPDWRLGDUWKULWLVUHIUDFWRU\WRDQWLWXPRXUQHFURVLVIDFWRU
ELRORJLFDOVUHVXOWVIURPDZHHNPXOWLFHQWUHUDQGRPLVHGSODFHER
FRQWUROOHGWULDO$QQ5KHXP'LV

'RXJDGRV0.LVVHO.6KHHUDQ77DN33&RQDJKDQ3*0ROD(0
6FKHWW*$PLWDO+1DYDUUR6DUDELD)+RX$HWDO$GGLQJWRFLOL]XPDE
RUVZLWFKLQJWRWRFLOL]XPDEPRQRWKHUDS\LQPHWKRWUH[DWHLQDGHTXDWH
UHVSRQGHUVZHHNV\PSWRPDWLFDQGVWUXFWXUDOUHVXOWVRID\HDU
UDQGRPLVHGFRQWUROOHGVWUDWHJ\WULDOLQUKHXPDWRLGDUWKULWLV$&7
5$<$QQ5KHXP'LV

%XUPHVWHU*5)HLVW(.HOOQHU+%UDXQ-,NLQJ.RQHUW&5XEEHUW5RWK
$(IIHFWLYHQHVVDQGVDIHW\RIWKHLQWHUOHXNLQUHFHSWRUDQWDJRQLVW
WRFLOL]XPDEDIWHUDQGZHHNVLQSDWLHQWVZLWKDFWLYHUKHXPDWRLG
DUWKULWLVWKHILUVWSKDVH,,,EUHDOOLIHVWXG\7$0$5$$QQ5KHXP'LV


-DLQ06DPXHOV-0XVFXORVNHOHWDOXOWUDVRXQGLQWKHGLDJQRVLVRI
UKHXPDWLFGLVHDVH%XOO1<8+RVS-W'LV

8OWUDVRXQGLQ$PHULFDQUKHXPDWRORJ\SUDFWLFHUHSRUWRIWKH
$PHULFDQ&ROOHJHRI5KHXPDWRORJ\PXVFXORVNHOHWDOXOWUDVRXQGWDVN
IRUFH$UWKULWLV&DUH5HV+RERNHQ

&KHXQJ33'RXJDGRV0*RVVHF/5HOLDELOLW\RIXOWUDVRQRJUDSK\WR
GHWHFWV\QRYLWLVLQUKHXPDWRLGDUWKULWLVDV\VWHPDWLFOLWHUDWXUH
UHYLHZRIVWXGLHVSDWLHQWV$UWKULWLV&DUH5HV+RERNHQ


0DQGO31DUHGR(:DNHILHOG5-&RQDJKDQ3*'
$JRVWLQR0$$
V\VWHPDWLFOLWHUDWXUHUHYLHZDQDO\VLVRIXOWUDVRXQGMRLQWFRXQWDQG
VFRULQJV\VWHPVWRDVVHVVV\QRYLWLVLQUKHXPDWRLGDUWKULWLV
DFFRUGLQJWRWKH20(5$&7ILOWHU-5KHXPDWRO

%DFNKDXV02KUQGRUI6.HOOQHU+6WUXQN-%DFNKDXV70+DUWXQJ:
6DWWOHU+$OEUHFKW..DXIPDQQ-%HFNHU.HWDO(YDOXDWLRQRIDQRYHO
MRLQWXOWUDVRXQGVFRUHLQGDLO\UKHXPDWRORJLFSUDFWLFHDSLORW
SURMHFW$UWKULWLV5KHXP

1DUHGR(5RGULJXH]0&DPSRV&5RGULJXH]+HUHGLD-00HGLQD-$
*LQHU(0DUWLQH]27R\RV)-5XL]75RV,HWDO9DOLGLW\
UHSURGXFLELOLW\DQGUHVSRQVLYHQHVVRIDWZHOYHMRLQWVLPSOLILHG
SRZHUGRSSOHUXOWUDVRQRJUDSKLFDVVHVVPHQWRIMRLQWLQIODPPDWLRQLQ
UKHXPDWRLGDUWKULWLV$UWKULWLV5KHXP

+DPD08HKDUD77DNDVH.,KDWD$8HGD$7DNHQR06KL]XNXLVKL.
7DWHLVKL8,VKLJDWVXER<3RZHU'RSSOHUXOWUDVRQRJUDSK\LVXVHIXOIRU
DVVHVVLQJGLVHDVHDFWLYLW\DQGSUHGLFWLQJMRLQWGHVWUXFWLRQLQ
UKHXPDWRLGDUWKULWLVSDWLHQWVUHFHLYLQJWRFLOL]XPDESUHOLPLQDU\GDWD
5KHXPDWRO,QW


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 32 of 33 
9HUVLRQ'$7( 

7D\ORU3&6WHXHU$*UXEHU-0F&OLQWRQ&&RVJURYH'2%ORPOH\0-
0DUVWHUV3$:DJQHU&/0DLQL518OWUDVRQRJUDSKLFDQG
UDGLRJUDSKLFUHVXOWVIURPDWZR\HDUFRQWUROOHGWULDORILPPHGLDWHRU
RQH\HDUGHOD\HGDGGLWLRQRILQIOL[LPDEWRRQJRLQJPHWKRWUH[DWH
WKHUDS\LQSDWLHQWVZLWKHURVLYHHDUO\UKHXPDWRLGDUWKULWLV$UWKULWLV
5KHXP

1DUHGR(0ROOHU,&UX]$&DUPRQD/*DUULGR-3RZHU'RSSOHU
XOWUDVRQRJUDSKLFPRQLWRULQJRIUHVSRQVHWRDQWLWXPRUQHFURVLV
IDFWRUWKHUDS\LQSDWLHQWVZLWKUKHXPDWRLGDUWKULWLV$UWKULWLV5KHXP


)XNDH-,VREH0.LWDQR$+HQPL06DNDPRWR)1DULWD$,WR7
0LWVX]DNL$6KLPL]X07DQLPXUD.HWDO5DGLRJUDSKLFSURJQRVLVRI
ILQJHUMRLQWGDPDJHSUHGLFWHGE\HDUO\DOWHUDWLRQLQV\QRYLDO
YDVFXODULW\LQSDWLHQWVZLWKUKHXPDWRLGDUWKULWLV3RWHQWLDOXWLOLW\RI
SRZHUGRSSOHUVRQRJUDSK\LQFOLQLFDOSUDFWLFH$UWKULWLV&DUH5HV
+RERNHQ

.DPLVKLPD76DJDZD$7DQLPXUD.6KLPL]X00DWVXKDVKL0
6KLQRKDUD0+DJLZDUD++HQPL01DULWD$7HUDH6HWDO6HPL
TXDQWLWDWLYHDQDO\VLVRIUKHXPDWRLGILQJHUMRLQWV\QRYLWLVXVLQJSRZHU
'RSSOHUXOWUDVRQRJUDSK\ZKHQWRSHUIRUPIROORZXSVWXG\DIWHU
WUHDWPHQWFRQVLVWLQJPDLQO\RIDQWLWXPRUQHFURVLVIDFWRUDOSKDDJHQW
6NHOHWDO5DGLRO

.XPH.$PDQR.<DPDGD6+DWWD..XZDED12KWD+9HU\HDUO\
LPSURYHPHQWVLQWKHZULVWDQGKDQGDVVHVVHGE\SRZHU'RSSOHU
VRQRJUDSK\SUHGLFWLQJODWHUIDYRUDEOHUHVSRQVHVLQWRFLOL]XPDE
WUHDWHGSDWLHQWVZLWKUKHXPDWRLGDUWKULWLV$UWKULWLV&DUH5HV+RERNHQ


=D\DW$6)UHHVWRQ-(&RQDJKDQ3*+HQVRU(0(PHU\3:DNHILHOG
5-'RHVMRLQWSRVLWLRQDIIHFW86ILQGLQJVLQLQIODPPDWRU\
DUWKULWLV"5KHXPDWRORJ\2[IRUG

/HH9=D\DW$:DNHILHOG5-7KHHIIHFWRIMRLQWSRVLWLRQRQ'RSSOHU
IORZLQILQJHUV\QRYLWLV$QQ5KHXP'LV

'RXJDGRV0-RXVVH-RXOLQ60LVWUHWWD)G
$JRVWLQR0$%DFNKDXV0
%HQWLQ-&KDOHV*&KDU\9DOFNHQDHUH,&RQDJKDQ3(WFKHSDUH)HWDO
(YDOXDWLRQRIVHYHUDOXOWUDVRQRJUDSK\VFRULQJV\VWHPVIRUV\QRYLWLV
DQGFRPSDULVRQWRFOLQLFDOH[DPLQDWLRQUHVXOWVIURPDSURVSHFWLYH
PXOWLFHQWUHVWXG\RIUKHXPDWRLGDUWKULWLV$QQ5KHXP'LV


+DPPHU+%%ROWRQ.LQJ3%DNNHKHLP9%HUJ7+6XQGW(.RQJWRUS
$.+DDYDUGVKROP($([DPLQDWLRQRILQWUDDQGLQWHUUDWHUUHOLDELOLW\
ZLWKDQHZXOWUDVRQRJUDSKLFUHIHUHQFHDWODVIRUVFRULQJRIV\QRYLWLV
LQSDWLHQWVZLWKUKHXPDWRLGDUWKULWLV$QQ5KHXP'LV


 


7RFLOL]XPDE8OWUDVRXQG6WXG\
 
3DJH 33 of 33 
9HUVLRQ'$7( 

$33(1',;$
6DIHW\5HSRUWLQJ)D[&RYHU6KHHW

 
SAFETY REPORTING FAX COVER SHEET 
Investigator Sponsored Trials 
 
SAE FAX No: (650) 225-4682 
Alternate Fax No: (650) 225-4683 
 
Study Number 
(Genentech study number) 

Principal Investigator 
 
Site Name 
 
 
Reporter name 
 
Reporter Telephone # 
 
Reporter Fax # 
 
 
 
Initial Report Date 
(DD/MON/YYYY) 
____ / _____ /_____ 
Follow-up Report Date 
(DD/MON/YYYY) 
____ / _____ /_____ 
 
 
Subject Initials 
(Please enter a dash if the patient has no 
middle name) 
____ - ____ -____ 
 
 
PLEASE PLACE MEDWATCH REPORT or IND SAFETY REPORT BEHIND THIS COVER 
SHEET 
 
 
Please contact Genentech Safety for any questions regarding SAE or IND 
Safety reporting at (888) 835-2555