Phase II Clinical Trial of Sunitinib in Sarcomas of the Central Nervous System
Phase: PHASE2
Conditions: Gliosarcoma, Central Nervous System Sarcoma
Sponsor: National Cancer Institute (NCI)


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV &&3URWRFRO18C0137
9HUVLRQ'DWH
1&71XPEHUNCT0364326 
7LWOH3KDVH,,6WXG\RI6XQLWLQLELQ6DUFRPDVRIWKH&HQWUDO1HUYRXV6\VWHP

*protocol number and NCT number added on title page 030922
1&,3ULQFLSDO,QYHVWLJDWRU


0DUN*LOEHUW0'$(
1HXUR2QFRORJ\%UDQFK
1DWLRQDO&DQFHU,QVWLWXWH
%XLOGLQJ5P$
2OG*HRUJHWRZQ5G
%HWKHVGD0'
3KRQH
(PDLOPDUNJLOEHUW#QLKJRY




&RPPHUFLDO$JHQW6XQLWLQLE0DODWHKHUHDIWHUUHIHUUHGWRDVVXQLWLQLEZLOOEHVXSSOLHGE\
3IL]HU
&RPPHUFLDO'HYLFHZ*7;%7PDQXIDFWXUHGE\$FWLJUDSKKHUHDIWHUUHIHUUHGWRDV
$FWLJUDSK$,VLQWKH'LDEHWHV(QGRFULQRORJ\DQG2EHVLW\%UDQFKRI1,''.ZLOOSURYLGHWKH
DFWLJUDSK\HTXLSPHQW


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

35e&,6

%DFNJURXQG
x *OLRVDUFRPDDQGSULPDU\&16VDUFRPDVDUHPDOLJQDQWEUDLQWXPRUVXQLIRUPO\
DVVRFLDWHGZLWKSRRURXWFRPH
x 7KHUHDUHQRNQRZQHIIHFWLYHPHGLFDOWKHUDSLHVIRUWKHVHFDQFHUV
x 6XQLWLQLELVDQRUDOO\DGPLQLVWHUHGVPDOOPROHFXOHWKDWLQKLELWVVLJQDOLQJRIPXOWLSOH
UHFHSWRUW\URVLQHNLQDVHVLQFOXGLQJWKRVHNQRZQWREHDFWLYDWHGLQ&16VDUFRPDV
2EMHFWLYHV
7RGHWHUPLQHWKHDQWLWXPRUHIIHFWRIVXQLWLQLELQUHFXUUHQWJOLRVDUFRPDVDQGSULPDU\&16
VDUFRPDVDVDVVHVVHGE\REMHFWLYHUHVSRQVHUDWH255
(OLJLELOLW\

3DWLHQWVZLWKKLVWRORJLFDOO\SURYHQJOLRVDUFRPDDQGSULPDU\&16VDUFRPDDWGLVHDVH
UHODSVHDIWHUIDLOLQJVWDQGDUGWKHUDS\VXUJHU\DQGLUUDGLDWLRQ

7XPRUWLVVXHEORFNVRUXQVWDLQHGVOLGHVVKRXOGEHDYDLODEOH

6XEMHFWVPXVWEH\HDUVROG

.DUQRIVN\SHUIRUPDQFHVWDWXVRI

3DWLHQWVPXVWKDYHDGHTXDWHRUJDQIXQFWLRQ

3DWLHQWVPXVWQRWKDYHUHFHLYHGW\URVLQHNLQDVHLQKLELWRUVLQWKHSDVW
'HVLJQ
x 7KLVLVDSURVSHFWLYHVLQJOHLQVWLWXWLRQVLQJOHDUPPXOWLFRKRUWSKDVH,,VWXG\RI
VXQLWLQLELQVXEMHFWVZLWKUHFXUUHQWJOLRVDUFRPDDQGSULPDU\&16VDUFRPDWKDWKDYH
IDLOHGSULRUVXUJHU\DQGLUUDGLDWLRQXQOHVVUDGLDWLRQWKHUDS\ZDVFRQWUDLQGLFDWHG
x 6XEMHFWVZLOOEHFODVVLILHGLQWRWKUHHFRKRUWV3ULPDU\JOLRVDUFRPD6HFRQGDU\
JOLRVDUFRPD3ULPDU\&16VDUFRPD&RKRUWH[SDQVLRQZLOOEHFDUULHGRXWDW
LQGLFDWLRQRISURPLVLQJUHVSRQVH
x 6XQLWLQLEZLOOEHDGPLQLVWHUHGRUDOO\XVLQJDFRQWLQXRXVVFKHGXOHDWPJSHUGD\ZLWK
GRVHDGMXVWPHQWVDOORZHGIRUWR[LFLW\IRUZHHNVZLWKZHHNRIIWRFRQVWLWXWHD
ZHHNF\FOHXQWLOGLVHDVHSURJUHVVLRQRUGHYHORSPHQWRILQWROHUDEOHVLGHHIIHFWV
x 7R[LFLW\ZLOOEHDVVHVVHGHYHU\F\FOHE\&7&$(YHUVLRQ


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

7$%/(2)&217(176
35e&,6 
7$%/(2)&217(176 
 
,1752'8&7,21 
 
6WXG\2EMHFWLYHV 
 
3ULPDU\2EMHFWLYH 
 
6HFRQGDU\2EMHFWLYHV 
 
([SORUDWRU\ 
 
%DFNJURXQGDQG5DWLRQDOH 
 
*OLRVDUFRPD 
 
3ULPDU\&16VDUFRPD 
 
6XQLWLQLE6XWHQW 
 
3DVW([SHULHQFH 
 
5DWLRQDOHIRU([SORUDWRU\6WXGLHV 
 
5DWLRQDOHIRU7KH3DWLHQW5HSRUWHG2XWFRPHV 
 
(/,*,%,/,7<$66(660(17$1'(152//0(17 
 
(OLJLELOLW\&ULWHULD 
 
,QFOXVLRQ&ULWHULD 
 
([FOXVLRQ&ULWHULD 
 
5HFUXLWPHQW6WUDWHJLHV 
 
6FUHHQLQJ(YDOXDWLRQ 
 
5HJLVWUDWLRQ3URFHGXUHV 
 
7UHDWPHQW$VVLJQPHQW3URFHGXUHV 
 
%DVHOLQH(YDOXDWLRQ 
 
678'<,03/(0(17$7,21 
 
6WXG\'HVLJQ 
 
2SWLRQDO$VVHVVPHQWRI)UHH/LYLQJ3K\VLFDO$FWLYLW\DQG6OHHS4XDOLW\ 
 
'RVH/LPLWLQJ7R[LFLW\'/7 
 
'UXJ$GPLQLVWUDWLRQ 
 
'RVH0RGLILFDWLRQV 
 
'RVH0RGLILFDWLRQ*XLGHOLQHVIRU6XQLWLQLE$VVRFLDWHG7R[LFLW\ 
 
6XSSRUWLYH&DUH*XLGHOLQHV 
 
4XHVWLRQQDLUHV 


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 
6WXG\&DOHQGDU 
 
&ULWHULDIRU5HPRYDOIURP3URWRFRO7KHUDS\DQG2II6WXG\&ULWHULD 
 
&ULWHULDIRU5HPRYDOIURP3URWRFRO7KHUDS\ 
 
2II6WXG\&ULWHULD 
 
2II3URWRFRO7KHUDS\DQG2II6WXG\3URFHGXUH 
 
&21&20,7$170(',&$7,2160($685(6 
 
%,263(&,0(1&2//(&7,21 
 
&RUUHODWLYH6WXGLHVIRU5HVHDUFK 
 
6DPSOH6WRUDJH7UDFNLQJDQG'LVSRVLWLRQ 
 
'$7$&2//(&7,21$1'(9$/8$7,21 
 
'DWD&ROOHFWLRQ 
 
'DWD6KDULQJ3ODQV 
 
+XPDQ'DWD6KDULQJ3ODQ 
 
5HVSRQVH&ULWHULD 
 
'HILQLWLRQV 
 
'LVHDVH3DUDPHWHUV 
 
(YDOXDWLRQRI%HVW2YHUDOO5HVSRQVH 
 
3URJUHVVLRQ)UHH6XUYLYDO 
 
5HVSRQVH5HYLHZ 
 
7R[LFLW\&ULWHULD 
 
6$)(7<5(3257,1*5(48,5(0(176'$7$$1'6$)(7<021,725,1*
3/$1 
 
'HILQLWLRQV 
 
$GYHUVH(YHQW 
 
6XVSHFWHGDGYHUVHUHDFWLRQ 
 
8QH[SHFWHGDGYHUVHUHDFWLRQ 
 
6HULRXV 
 
6HULRXV$GYHUVH(YHQW 
 
'LVDELOLW\ 
 
/LIHWKUHDWHQLQJDGYHUVHGUXJH[SHULHQFH 
 
3URWRFRO'HYLDWLRQ1,+'HILQLWLRQ 
 
1RQFRPSOLDQFH1,+'HILQLWLRQ 
 8QDQWLFLSDWHG3UREOHP 


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 
1&,,5%DQG&OLQLFDO'LUHFWRU5HSRUWLQJ 
 
1&,,5%DQG1&,&'([SHGLWHG5HSRUWLQJRI8QDQWLFLSDWHG3UREOHPVDQG
'HDWKV  
 
1&,,5%5HTXLUHPHQWVIRU3,5HSRUWLQJDW&RQWLQXLQJ5HYLHZ 
 
6DIHW\5HSRUWLQJ&ULWHULDWRWKH3KDUPDFHXWLFDO&ROODERUDWRUV 
 
5HSRUWLQJRI6HULRXV$GYHUVH(YHQWV 
 
3UHJQDQF\([SRVXUHRU/DFNRI(IIHFW 
 
+\¶V/DZ&DVHV 
 
5HSRUWLQJ 
 
'DWDDQG6DIHW\0RQLWRULQJ3ODQ 
 
3ULQFLSDO,QYHVWLJDWRU5HVHDUFK7HDP 
 
67$7,67,&$/&216,'(5$7,216 
 
*HQHUDO$SSURDFK 
 
6DPSOH6L]H-XVWLILFDWLRQ 
 
6WDWLVWLFDO$QDO\VLV 
 
3DWLHQW5HSRUWHG2XWFRPHV 
 
&2//$%25$7,9($*5((0(176 
 
$JUHHPHQW7\SH 
 +80$168%-(&763527(&7,216 
 
5DWLRQDOH)RU6XEMHFW6HOHFWLRQ 
 
3DUWLFLSDWLRQ2I&KLOGUHQ 
 
3DUWLFLSDWLRQ2I:RPHQ2I&KLOG%HDULQJ3RWHQWLDO 
 
3DUWLFLSDWLRQIRU+,93DWLHQWV 
 
3DUWLFLSDWLRQRI6XEMHFWV8QDEOHWR*LYH&RQVHQW 
 
(YDOXDWLRQRI%HQHILWVDQG5LVNV'LVFRPIRUWV 
 $OWHUQDWLYH$SSURDFKHVRU7UHDWPHQWV 
 3URFHGXUHIRU3URWHFWLQJ$JDLQVWRU0LQLPL]LQJ$Q\3RWHQWLDO5LVNV 
 
5LVNV%HQHILWV$QDO\VLV 
 %HQHILWV 
 5LVNV 
 5LVNV%HQHILWV$QDO\VLV 
 
&RQVHQW3URFHVVDQG'RFXPHQWDWLRQ 
 ,QIRUPHG&RQVHQWRI1RQ(QJOLVK6SHDNLQJ6XEMHFWV 


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 3+$50$&(87,&$/DQG0(',&$/'(9,&(,1)250$7,21 
 
5DWLRQDOHIRU,1'([HPSWLRQ 
 
6XQLWLQLE0DODWH6XWHQW 
 6RXUFH 
 7R[LFLW\ 
 )RUPXODWLRQDQG3UHSDUDWLRQ 
 6WDELOLW\DQG6WRUDJH 
 ,QFRPSDWLELOLWLHV 
 
Z*7;%7 
 3URGXFW'HVFULSWLRQ 
 0DQXIDFWXUHU$FWL*UDSK 
 'LPHQVLRQV[[FP 
 :HLJKWJUDPV 
 6RXUFH 
 6WRUDJH 
 $GPLQLVWUDWLRQ 
 3UHFDXWLRQV 
 5()(5(1&(6 
 $33(1',; 
 
3HUIRUPDQFH6WDWXV&ULWHULD 
 
3LOODQG%ORRG3UHVVXUH'LDU\ 
 
0'$QGHUVRQ6\PSWRP,QYHQWRU\0'$6,%7 
 
$FWLJUDSK\3DWLHQW7HDFKLQJ7RRO 
 
0DQDJHPHQWRI+\SHUWHQVLRQ,QGXFHGE\9(*),QKLELWRUV 





$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 ,1752'8&7,21

678'<2%-(&7,9(6
 3ULPDU\2EMHFWLYH
7RGHWHUPLQHWKHDQWLWXPRUHIIHFWRIVXQLWLQLELQUHFXUUHQWJOLRVDUFRPDVDQGSULPDU\&16
VDUFRPDVDVDVVHVVHGE\REMHFWLYHUHVSRQVHUDWH255
 6HFRQGDU\2EMHFWLYHV

7RGHWHUPLQHWKHPRQWKDQGPHGLDQSURJUHVVLRQIUHHVXUYLYDOUDWHV

7RGHWHUPLQHWKHDGYHUVHHYHQWUDWHRIVXQLWLQLELQSDWLHQWVZLWKUHFXUUHQW
JOLRVDUFRPDDQGSULPDU\&16VDUFRPD

7RHYDOXDWHDUFKLYDOWXPRUWLVVXHIRUDFWLYDWLRQRIVLJQDOLQJSDWKZD\VWDUJHWHG
E\VXQLWLQLEWRHVWDEOLVKSRWHQWLDOELRPDUNHUVRIUHVSRQVH

7RSHUIRUPEURDGXQELDVHGPROHFXODUSURILOLQJRIDUFKLYDOWXPRUWLVVXHVWR
LGHQWLI\SRWHQWLDOQRYHOELRPDUNHUVRIUHVSRQVHWRVXQLWLQLE

7RHYDOXDWHUDGLRORJLFDOSDUDPHWHUVVXFKDVSHUIXVLRQDQGG\QDPLFFRQWUDVW
HQKDQFHG05,EHIRUHDQGGXULQJWUHDWPHQWZLWKVXQLWLQLE

7RORQJLWXGLQDOO\HYDOXDWHSDWLHQWUHSRUWHGRXWFRPHPHDVXUHVXVLQJVHOIUHSRUWHG
V\PSWRPVHYHULW\DQGLQWHUIHUHQFHZLWKGDLO\DFWLYLWLHVXVLQJWKH0'$6,%7
 ([SORUDWRU\

%ORRGZLOOEHFROOHFWHGWRHYDOXDWHSUHVHQFHRIDQGFKDQJHVWRFLUFXODWLQJ9(*)5
3/*),/,/+*)EDVLF)*)FLUFXODWLQJWXPRUVFHOOVHQGRWKHOLDOSURJHQLWRUV
PDWXUHDSRSWRWLFHQGRWKHOLDOFHOOVUHJXODWRU\7FHOOVH[KDXVWHG&'7FHOOVP\HORLG
GHULYHGVXSSUHVVRUFHOOV0'6&DQG7K7K7FHOOV,PPXQRSKHQRW\SLQJ
HYDOXDWLRQVZLOOEHSHUIRUPHGXSRQDYDLODELOLW\RIWXPRUVDPSOHV

7RDVVHVVIUHHOLYLQJSK\VLFDODFWLYLW\DQGVOHHSTXDOLW\2SWLRQDO

%$&.*5281'$1'5$7,21$/(
7KLVLVDQ,QYHVWLJDWRU,QLWLDWHG5HVHDUFKVWXG\WRHYDOXDWHWKHDQWLWXPRUHIIHFWRIVXQLWLQLELQ
VXEMHFWVZLWKVDUFRPDVRIWKHFHQWUDOQHUYRXVV\VWHP
 *OLRVDUFRPD
*OLRVDUFRPDWXPRUFODVVLILHGDVDUDUHYDULDQWRIJOLREODVWRPDGHPRQVWUDWHVELSKDVLFJOLDODQG
PHVHQFK\PDOGLIIHUHQWLDWLRQ3ULPDU\JOLRVDUFRPDLVDGHQRYRQHXURHSLWKHOLDOWXPRUWKDW
H[KLELWVGXDOJOLDODQGVDUFRPDWRXVFRPSRQHQWVDWLQLWLDOGLDJQRVLV>@2QRFFDVLRQ
JOLREODVWRPDLQWKHUHFXUUHQWVHWWLQJPD\WUDQVLWLRQIURPW\SLFDOJOLDOSKHQRW\SH*)$3
SRVLWLYHWRDWXPRUZLWKUHWLFXOLQULFKVDUFRPDWRXVPHVHQFK\PDOIHDWXUHVVHFRQGDU\
JOLRVDUFRPD7KHVHWXPRUVDUHPRUHFRPPRQLQPHQDQGRIWHQDULVHLQWKHWHPSRUDOOREHV
:KLOHH[WUDFUDQLDOPHWDVWDVLVIURPJOLREODVWRPDLVUDUHJOLRVDUFRPDVKDYHDSURSHQVLW\WR
GLVVHPLQDWHH[WUDFUDQLDOO\OLNHO\GXHWRWKHVDUFRPDWRXVFRPSRQHQW3DWLHQWVZLWKJOLRVDUFRPD
H[SHULHQFHSRRURXWFRPHZLWKPHGLDQVXUYLYDOUDQJLQJIURPWRPRQWKV>@


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

7KHXQGHUO\LQJWXPRUELRORJ\RIJOLRVDUFRPDDSSHDUVWREHGLVWLQFWFRPSDUHGWRJOLREODVWRPD
)UHTXHQF\RI73PXWDWLRQLVKLJKHUDQGRQO\RQYHU\UDUHRFFDVLRQ(*)5DPSOLILFDWLRQLV
SUHVHQW,QDGGLWLRQ0*07PHWK\ODWLRQDQG,'+PXWDWLRQVDUHUDUHLQJOLRVDUFRPDV>@0RVW
SDWLHQWVWKDWSUHVHQWZLWKJOLRVDUFRPDDUHWUHDWHGVLPLODUO\WRWKRVHZLWKJOLREODVWRPDLQVSLWHRI
WKHOLNHO\GLIIHUHQFHVLQWXPRUSDWKRJHQHVLVDQGWKHUHIRUHWKHUDSHXWLFUHVSRQVHSDWWHUQ
7UHDWPHQWRSWLRQVIRUSDWLHQWVZLWKUHFXUUHQWJOLRVDUFRPDDUHH[WUHPHO\OLPLWHG+RZHYHU
JOLRVDUFRPDVRIWHQSRVVHVVSODWHOHWGHULYHGJURZWKIDFWRUUHFHSWRU3'*)5.,76&)
DXWRFULQHDFWLYDWLRQORRSVVXJJHVWLQJWKHSRWHQWLDOXWLOLW\RIFHUWDLQW\URVLQHNLQDVH
LQKLELWRUV>@
 3ULPDU\&16VDUFRPD
3ULPDU\VDUFRPDVRIWKH&16DUHUDUHWXPRUVaRIDOOLQWUDFUDQLDOWXPRUVZLWKOLWWOH
NQRZQFRQFHUQLQJWKHXQGHUO\LQJELRORJ\7KH\DUHEHOLHYHGWRDULVHIURPPHVHQFK\PDO
WLVVXHVZLWKLQWKHLQWUDFUDQLDOFDYLW\VXFKDVEORRGYHVVHOVPHQLQJHVRUERQH$VVXFKWKHVH
WXPRUVDUHKLVWRORJLFDOO\VLPLODUWRVDUFRPDVRIVRIWWLVVXHRUERQH7KHFXUUHQW:+2
FODVVLILFDWLRQUHFRJQL]HVVSHFLILFGLIIHUHQWLDWLRQILEURVDUFRPDVROLWDU\ILEURXVWXPRU
FKRQGURVDUFRPDRVWHRVDUFRPDOLSRVDUFRPDLQIODPPDWRU\PDOLJQDQWP\RILEUREODVWLFWXPRU
OHLRP\RVDUFRPDUKDEGRP\RVDUFRPDDQJLRVDUFRPDDQGRWKHU&16VDUFRPDV$OWKRXJK
GHWDLOHGVWXGLHVRIWKHVHWXPRUVDUHOLPLWHGUHSRUWVLQGLFDWHWKH\PD\EHLQSDUWGULYHQE\
YDVFXODUHQGRWKHOLDOJURZWKIDFWRU9(*)>@7UHDWPHQWFRQVLVWVRIVXUJLFDOUHVHFWLRQZKHQ
DFFHVVLEOHIROORZHGE\LUUDGLDWLRQ7KHUHDUHQRNQRZQHIIHFWLYHPHGLFDOWKHUDSLHVIRUSULPDU\
&16VDUFRPDV
 6XQLWLQLE6XWHQW
6XQLWLQLEPDODWHLVDSSURYHGPXOWLQDWLRQDOO\IRUWKHWUHDWPHQWRIJDVWURLQWHVWLQDOVWURPDOWXPRU
DIWHUGLVHDVHSURJUHVVLRQRQRULQWROHUDQFHWRLPDWLQLEDGYDQFHGUHQDOFHOOFDUFLQRPDDQG
XQUHVHFWDEOHZHOOGLIIHUHQWLDWHGPHWDVWDWLFSDQFUHDWLFQHXURHQGRFULQHWXPRUV1(76XQLWLQLE
LVDQRUDOO\DGPLQLVWHUHGVPDOOPROHFXOHWKDWLQKLELWVPXOWLSOHUHFHSWRUW\URVLQHNLQDVHV57.V
VRPHRIZKLFKDUHLPSOLFDWHGLQWXPRUJURZWKSDWKRORJLFDQJLRJHQHVLVDQGPHWDVWDWLF
SURJUHVVLRQRIFDQFHU6XQLWLQLEZDVHYDOXDWHGIRULWVLQKLELWRU\DFWLYLW\DJDLQVWDYDULHW\RI
NLQDVHV!NLQDVHVDQGZDVLGHQWLILHGDVDQLQKLELWRURI3'*)5Į3'*)5ȕ9(*)5
9(*)59(*)5VWHPFHOOIDFWRUUHFHSWRU.,7)PVOLNHW\URVLQHNLQDVH)/7FRORQ\
VWLPXODWLQJIDFWRUUHFHSWRU7\SH&6)5DQGWKHJOLDOFHOOOLQHGHULYHGQHXURWURSKLFIDFWRU
UHFHSWRU5(76XQLWLQLELQKLELWLRQRIWKHDFWLYLW\RIWKHVH57.VKDVEHHQGHPRQVWUDWHGLQ
ELRFKHPLFDODQGFHOOXODUDVVD\VDQGLQKLELWLRQRIIXQFWLRQKDVEHHQGHPRQVWUDWHGLQFHOO
SUROLIHUDWLRQDVVD\V7KHSULPDU\PHWDEROLWHH[KLELWVVLPLODUSRWHQF\FRPSDUHGWRVXQLWLQLELQ
ELRFKHPLFDODQGFHOOXODUDVVD\V6XQLWLQLELQKLELWHGWKHSKRVSKRU\ODWLRQRIPXOWLSOH57.V
3'*)5ȕ9(*)5.,7LQWXPRU[HQRJUDIWVH[SUHVVLQJ57.WDUJHWVLQYLYRDQG
GHPRQVWUDWHGLQKLELWLRQRIWXPRUJURZWKRUWXPRUUHJUHVVLRQDQGRULQKLELWHGPHWDVWDVHVLQ
VRPHH[SHULPHQWDOPRGHOVRIFDQFHU6XQLWLQLEGHPRQVWUDWHGWKHDELOLW\WRLQKLELWJURZWKRI
WXPRUFHOOVH[SUHVVLQJG\VUHJXODWHGWDUJHW57.V3'*)55(7RU.,7LQYLWURDQGWRLQKLELW
3'*)5ȕDQG9(*)5GHSHQGHQWWXPRUDQJLRJHQHVLVLQYLYR6XQLWLQLELVFOLQLFDOO\LQGLFDWHG
IRUWKHWUHDWPHQWRIDGYDQFHGUHQDOFHOOFDUFLQRPDJDVWURLQWHVWLQDOVWURPDOWXPRU
$VRI2FWREHUVXEMHFWVLQFOXGLQJKHDOWK\VXEMHFWVVXEMHFWVZLWKUHQDOLPSDLUPHQW
VXEMHFWVZLWKKHSDWLFLPSDLUPHQWVXEMHFWVZLWKDFXWHP\HORLGOHXNHPLDDQGVXEMHFWVZLWKVROLG


$EEUHYLDWHG7LWOH 3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH
PDOLJQDQWWXPRUVLQFRPSOHWHGRURQJRLQJFOLQLFDOVWXGLHVKDGUHFHLYHGDWOHDVWRQHGRVHRI
VXQLWLQLE3KDUPDFRNLQHWLFVWXGLHVLQGLFDWHVXQLWLQLELVDEOHSHQHWUDWHWKHEORRGEUDLQEDUULHU>
@

3DVW([SHULHQFH
$\HDUROGZRPDQZLWKUHFXUUHQWSULPDU\&16VDUFRPDZDVUHIHUUHGWRWKH12%2XWSDWLHQW
&OLQLF6XUJLFDOUHVHFWLRQZDVQRWDIHDVLEOHRSWLRQDQGVKHIDLOHGUHFHQWUDGLDWLRQWKHUDS\
%DVHGRQSUHYLRXVH[SHULHQFHZLWK&16VDUFRPDVZHGHFLGHGWRSURFHHGZLWKDWULDORI
VXQLWLQLE$IWHUF\FOHZHHNVRIWUHDWPHQW05,VKRZHGUHVSRQVHVHHSDQHOEHORZ)LJXUH

)LJXUH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 5DWLRQDOHIRU([SORUDWRU\6WXGLHV
6HUXPPDUNHUVRIDQJLRJHQHVLV$SRWHQWLDOPHFKDQLVPIRUVXQLWLQLEUHVLVWDQFHLVWKH
XSUHJXODWLRQRIDOWHUQDWLYHSURWHLQVDQGRUSDWKZD\VWKDWFRXOGGULYHWXPRUDQJLRJHQHVLVDQGRU
JURZWKLQGHSHQGHQWRI9(*)3UHFOLQLFDOVWXGLHVLQYROYLQJ5&&DQGQRQ5&&PRGHOVKDYH
LGHQWLILHGDYDULHW\RIFDQGLGDWHSURWHLQVWKDWPD\EHLQYROYHGLQUHVLVWDQFHWR9(*)WKHUDS\
$PRQJWKHVHSURWHLQVZKLFKVWLPXODWHDQJLRJHQHVLVGLUHFWO\RULQGLUHFWO\DUHILEUREODVWJURZWK
IDFWRU)*)KHSDWRF\WHJURZWKIDFWRU+*)DQGSODFHQWDOJURZWKIDFWRU3O*):HSURSRVH
WRH[SORUHWKHSRWHQWLDOXWLOLW\RIWKHVHSURWHLQVDVELRPDUNHUVRISKDUPDFRORJLFDODQGFOLQLFDO
DFWLYLW\RIVXQLWLQLELQ&16VDUFRPDV7KHVHDVVD\VZLOOEHSHUIRUPHGLQWKH7UHSHO
/DERUDWRU\'7%1&,
3HULSKHUDOEORRGLPPXQHPRQLWRULQJ,QDGGLWLRQWRPRGXODWLRQRIDQJLRJHQLFDFWLYLW\VXQLWLQLE
DOVRDSSHDUVWRUHJXODWHNH\DQWLWXPRULPPXQHUHVSRQVH6XQLWLQLEKDVEHHQVKRZQWRGHFUHDVH
WKHIUHTXHQF\RIUHJXODWRU\7FHOOV7UHJVDQGP\HORLGGHULYHGVXSSUHVVRUFHOOV0'6&VLQ
PHWDVWDWLFUHQDOFHOOFDUFLQRPDSDWLHQWV>@,WKDVEHHQVKRZQWKDWGHYHORSPHQWRIVXQLWLQLE
UHVLVWDQFHLVSDUWO\PHGLDWHGE\WKHVXUYLYDORI0'6&VWKHUHE\SURYLGLQJVXVWDLQHGLPPXQH
VXSSUHVVLRQDQGDQJLRJHQHVLV>@6XQLWLQLEKDVDOVRVKRZQWRVKLIW7KHOSHUFHOOVWRZDUGD7
KHOSHU7KSRODUL]HGUHVSRQVHDQGLQFUHDVHWKH7KFHOO7KHOSHU7KFHOOUDWLR$
VLJQLILFDQWGHFUHDVHLQWKH7K7KUDWLRZDVVHHQDIWHUVXQLWLQLEWUHDWPHQWLQWKH3)6VKRUW
JURXSLQP5&&>@([KDXVWHG&'7FHOOVZKLFKH[SUHVVLQKLELWRU\UHFHSWRUV3'DQG
7LPZHUHIRXQGLQFDQFHUSDWLHQWVDQGWKHUDSHXWLFUHVSRQVHZDVFRUUHODWHGZLWKGHFOLQHLQ
7LP&'7FHOOV3HULSKHUDOEORRGZLOOEHFROOHFWHGLQWRRQHPO&37WXEH3HULSKHUDO
EORRGPRQRQXFOHDUFHOOV3%0&ZLOOEHDVVHVVHGXVLQJPXOWLSDUDPHWHUIORZF\WRPHWU\IRU
LPPXQHVXEVHWVLQFOXGLQJEXWQRWQHFHVVDULO\OLPLWHGWR&'7FHOOV&')R[S7FHOOV
7UHJVPRQRF\WHVXEVHWV0'6&VXEVHWV$VVHVVPHQWZLOOLQFOXGHIXQFWLRQDOPDUNHUVLH3'
7LP&7/$3'/+/$'5DQGRU&'7KHUHIRUHPRQLWRULQJLPPXQHVXEVHWVLQ
&16VDUFRPDSDWLHQWVSUHDQGSRVWVXQLWLQLEWKHUDS\PD\FRQWULEXWHWRLPSURYHG
XQGHUVWDQGLQJRIVXQLWLQLEDQGSRVVLEO\LQIRUPIXWXUHVWXGLHV
&LUFXODWLQJ(QGRWKHOLDO&HOOV&(&DQG(QGRWKHOLDO3URJHQLWRU&HOOV&(3&(&VKDYH
HPHUJHGDVDSRWHQWLDOO\XVHIXOPDUNHUWRDVVHVVDQWLDQJLRJHQLFWKHUDS\$WOHDVWWZRGLVWLQFW
SRSXODWLRQVRI&(&VKDYHEHHQLGHQWLILHGERQHPDUURZGHULYHG&(3FHOOVDQGPDWXUH&(&V
&(3FHOOVEHDUDQWLJHQVWKDWLGHQWLI\WKHPDVHQGRWKHOLDOFHOOVVXFKDV9(*)5)ONDQG
&'DVZHOODVDQWLJHQVIRUVWHPFHOOVVXFKDV&'&'DQG&'8SRQDSSURSULDWH
VWLPXODWLRQERQHPDUURZGHULYHGHQGRWKHOLDOSURJHQLWRUFHOOVPLJUDWHWRWKHFLUFXODWLRQZKHUH
WKH\DUHUHIHUUHGWRDV&(3FHOOV&(3FHOOVKDYHEHHQVKRZQWRLQILOWUDWHKXPDQWXPRUVDQG
JLYHULVHWRWXPRUQHRYDVFXODWXUH)XUWKHU9(*)5VLJQDOLQJLVWKRXJKWWRPRELOL]H&(&V
ZKLFKLVFRQVRQDQWZLWKWKHREVHUYDWLRQWKDW&(&VDUHLQFUHDVHGLQSDWLHQWVZLWKDFWLYHFDQFHU
+RZVXQLWLQLEPD\DIIHFW&(&VDQG&(3VLVXQFOHDU7RH[SORUHWKLVSUHWUHDWHGDQGSRVW
WUHDWHGVDPSOHVZLOOEHREWDLQHGWRSHUIRUP&(&&(3DQDO\VHVE\PXOWLSDUDPHWULFIORZ
F\WRPHWU\LQWKH7UHSHO/DERUDWRU\
 5DWLRQDOHIRU7KH3DWLHQW5HSRUWHG2XWFRPHV
7KLVVWXG\VHHNVWRHVWDEOLVKHIIHFWLYHWKHUDS\IRUVDUFRPDVRIWKH&16:HK\SRWKHVL]HWKDW
VLQJOHDJHQWVXQLWLQLEZLOOUHVXOWLQDQWLWXPRUDFWLYLW\+RZHYHUJLYHQWKHSRWHQWLDOWR[LFLW\RI
VXQLWLQLELWZLOOEHLPSRUWDQWWRGHWHUPLQHZKHWKHUDQ\GHWHUPLQHGDQWLWXPRUHIIHFWLV


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

DVVRFLDWHGZLWKLPSURYHPHQWVLQV\PSWRPVRUZKHWKHUDZRUVHQLQJRIV\PSWRPVRIIVHWVWKH
LQFUHDVHLQVXUYLYDO
3UHFHGHQFHIRUPHDVXULQJ³QRQWKHUDSHXWLF´HQGSRLQWVH[LVWVLQRQFRORJ\UHVHDUFK)RU
H[DPSOH*HPFLWDELQHZDVDSSURYHGE\WKH)'$SDUWLDOO\DVDFRQVHTXHQFHRIWKHGHFUHDVHLQ
SDLQUHSRUWHGLQSDQFUHDWLFSDWLHQWVZKRZHUHWUHDWHGQRWRQWKHEDVLVRIVXUYLYDOLPSURYHPHQW
ZKLFKZDVPRGHVWDWEHVW7KHUHKDYHEHHQHIIRUWVLQQHXURRQFRORJ\WRHYDOXDWHVHFRQGDU\
HQGSRLQWVXVLQJYDOLGDWHGLQVWUXPHQWVDVDQDGGLWLRQDOLQGLFDWRURIEHQHILW
7KH0'$QGHUVRQ6\PSWRP,QYHQWRU\%UDLQ7XPRU0RGXOH0'$6,%7DOORZVWKHVHOI
UHSRUWLQJRIV\PSWRPVHYHULW\DQGLQWHUIHUHQFHZLWKGDLO\DFWLYLWLHV7KH0'$6,%7KDV
GHPRQVWUDWHGUHOLDELOLW\DQGYDOLGLW\LQWKHDGXOWSULPDU\EUDLQWXPRUSDWLHQWSRSXODWLRQ>@
7KLVWRROUHSUHVHQWVDPRGLILFDWLRQRIWKHZLGHO\XVHGDQGYDOLGDWHG0'$6,ZLWKSDUWLFXODU
DWWHQWLRQWRV\PSWRPVFRPPRQLQSDWLHQWVZLWKEUDLQWXPRUV7KHDYDLODELOLW\RIYDOLGDWHG
LQVWUXPHQWVSURYLGHVDQRSSRUWXQLW\WRSURVSHFWLYHO\DVVHVVWKHLPSDFWRIWUHDWPHQWERWK
SRVLWLYHDQGQHJDWLYHRQSDWLHQWV7KHHYDOXDWLRQRIV\PSWRPEXUGHQLQWKLVVWXG\ZLOODVVLVWLQ
ILQGLQJWKHEHVWSRVVLEOHWUHDWPHQWZLWKWKHOHDVWWR[LFLW\

(/,*,%,/,7<$66(660(17$1'(152//0(17

(/,*,%,/,7<&5,7(5,$
 ,QFOXVLRQ&ULWHULD
 3DWLHQWVPXVWKDYHKLVWRORJLFDOO\FRQILUPHGJOLRVDUFRPDSULPDU\RUVHFRQGDU\RU
SULPDU\FHQWUDOQHUYRXVV\VWHPVDUFRPDFRQILUPHGE\WKH/DERUDWRU\RI3DWKRORJ\
1&,
 3DWLHQWVPXVWKDYHPHDVXUDEOHGLVHDVHGHILQHGDVDWOHDVWRQHOHVLRQWKDWFDQEH
DFFXUDWHO\PHDVXUHGELGLPHQVLRQDOO\E\05,RU&7VFDQLI05,LVFRQWUDLQGLFDWHG
6HH6HFWLRQIRUWKHHYDOXDWLRQRIPHDVXUDEOHGLVHDVH
 3DWLHQWVPXVWKDYHIDLOHGVWDQGDUGWKHUDS\FRQVLVWLQJRIVXUJHU\LUUDGLDWLRQDQG
FKHPRWKHUDS\LILQGLFDWHG
 $JH!\HDUV
 .DUQRIVN\!VHH$SSHQGL[
 3DWLHQWVPXVWKDYHQRUPDORUJDQDQGPDUURZIXQFWLRQDVGHILQHGEHORZ
OHXNRF\WHV 




!PF/
DEVROXWHQHXWURSKLOFRXQW 
!PF/
SODWHOHWV





!PF/
WRWDOELOLUXELQ




ZLWKLQQRUPDOLQVWLWXWLRQDOOLPLWV
$676*27$/76*37
;LQVWLWXWLRQDOXSSHUOLPLWRIQRUPDO
FUHDWLQLQH





ZLWKLQQRUPDOLQVWLWXWLRQDOOLPLWV

25
FUHDWLQLQHFOHDUDQFH


!P/PLQPIRUSDWLHQWVZLWK
FUHDWLQLQHOHYHOVDERYHLQVWLWXWLRQDOQRUPDO


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 3DWLHQWVPXVWKDYHWKHDELOLW\WRXQGHUVWDQGDQGWKHZLOOLQJQHVVWRVLJQDZULWWHQ
LQIRUPHGFRQVHQWGRFXPHQWLQGLFDWLQJWKDWWKH\DUHDZDUHRIWKHLQYHVWLJDWLRQDOQDWXUH
RIWKLVVWXG\
 7KHHIIHFWVRIVXQLWLQLERQWKHGHYHORSLQJKXPDQIHWXVDUHXQNQRZQ)RUWKLVUHDVRQ
DQGEHFDXVHDQWLDQJLRJHQLFDJHQWVDUHNQRZQWREHWHUDWRJHQLFZRPHQRIFKLOG
EHDULQJSRWHQWLDODQGPHQPXVWDJUHHWRXVHDGHTXDWHFRQWUDFHSWLRQKRUPRQDORU
EDUULHUPHWKRGRIELUWKFRQWURODEVWLQHQFHSULRUWRVWXG\HQWU\DQGIRUWKHGXUDWLRQRI
VWXG\SDUWLFLSDWLRQ6KRXOGDZRPDQEHFRPHSUHJQDQWRUVXVSHFWVKHLVSUHJQDQWZKLOH
VKHRUKHUSDUWQHULVSDUWLFLSDWLQJLQWKLVVWXG\VKHVKRXOGLQIRUPKHUWUHDWLQJSK\VLFLDQ
LPPHGLDWHO\
 7XPRUWLVVXHEORFNVRUDWOHDVWXQVWDLQHGVOLGHVIURPWKHGLDJQRVLVVKRXOGEH
DYDLODEOH
$WWKHWLPHRIUHJLVWUDWLRQDOOVXEMHFWVPXVWEHUHPRYHGGD\VIURPDQ\
LQYHVWLJDWLRQDODJHQWV
 ([FOXVLRQ&ULWHULD
 3DWLHQWVZKRDUHUHFHLYLQJDQ\RWKHULQYHVWLJDWLRQDODJHQWV
 8QFRQWUROOHGLQWHUFXUUHQWLOOQHVVLQFOXGLQJEXWQRWOLPLWHGWRRQJRLQJRUDFWLYH
LQIHFWLRQV\PSWRPDWLFFRQJHVWLYHKHDUWIDLOXUHXQVWDEOHDQJLQDSHFWRULVFDUGLDF
DUUK\WKPLDRUSV\FKLDWULFLOOQHVVVRFLDOVLWXDWLRQVWKDWZRXOGOLPLWFRPSOLDQFHZLWK
VWXG\UHTXLUHPHQWV
 3ULRUXVHRIW\URVLQHNLQDVHLQKLELWRUVRU9(*)LQKLELWLRQ
 3DWLHQWVZKRDUHUHFHLYLQJVWURQJ&<3LQGXFHUVRULQKLELWRUVDUHLQHOLJLEOH
 3UHJQDQWZRPHQDUHH[FOXGHGIURPWKLVVWXG\EHFDXVHVXQLWLQLEKDVSRWHQWLDOIRU
WHUDWRJHQLFRUDERUWLIDFLHQWHIIHFWV%HFDXVHWKHUHLVDQXQNQRZQEXWSRWHQWLDOULVNIRU
DGYHUVHHYHQWVLQQXUVLQJLQIDQWVVHFRQGDU\WRWUHDWPHQWRIWKHPRWKHUZLWKVXQLWLQLE
EUHDVWIHHGLQJVKRXOGEHGLVFRQWLQXHGLIWKHPRWKHULVWUHDWHGZLWKVXQLWLQLE
 3DWLHQWVZLWKNQRZQ+,9KLVWRU\RQFRPELQDWLRQDQWLUHWURYLUDOWKHUDS\DUHLQHOLJLEOH
EHFDXVHRIWKHSRWHQWLDOIRUSKDUPDFRNLQHWLFLQWHUDFWLRQVZLWKVXQLWLQLE,QDGGLWLRQ
WKHVHSDWLHQWVDUHDWLQFUHDVHGULVNRIOHWKDOLQIHFWLRQVZKHQWUHDWHGZLWKPDUURZ
VXSSUHVVLYHWKHUDS\
 8QFRQWUROOHGK\SHUWHQVLRQޓPP+JZKLOHRQDQWLK\SHUWHQVLYHPHGLFDWLRQV
 1HZ<RUN+HDUW$VVRFLDWLRQFODVV,,RUJUHDWHUFRQJHVWLYHKHDUWIDLOXUH
 6HULRXVFDUGLDFDUUK\WKPLDUHTXLULQJPHGLFDWLRQ
%DVHOLQHHFKRFDUGLRJUDPZLWKHMHFWLRQIUDFWLRQޒRUGHFUHDVHIURPDSULRU
VWXG\
47FLQWHUYDOޓPVHFRQEDVHOLQH(.*
3DWLHQWVZKRUHTXLUHXVHRIWKHUDSHXWLFGRVHVRIFRXPDULQGHULYDWLYHDQWLFRDJXODQWV
VXFKDVZDUIDULQDUHH[FOXGHGDOWKRXJKGRVHVRIXSWRPJGDLO\DUHSHUPLWWHGIRU


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

SURSK\OD[LVRIWKURPERVLV1RWH/RZPROHFXODUZHLJKWKHSDULQLVSHUPLWWHGSURYLGHG
WKHSDWLHQW¶V,15LV
3UHYLRXVH[SRVXUHWRDQWKUDF\FOLQHV
 5HFUXLWPHQW6WUDWHJLHV
%RWKPHQDQGZRPHQRIDOOUDFHVDQGHWKQLFJURXSVDUHHOLJLEOHIRUWKLVVWXG\3RWHQWLDO
VXEMHFWVZLOOEHLGHQWLILHGIURPUHIHUUDOVWRWKH1HXUR2QFRORJ\&OLQLF

6&5((1,1*(9$/8$7,21
'RFXPHQWDWLRQFRQILUPDWLRQRIWXPRUGLDJQRVLVE\WKH1&,/DERUDWRU\RI3DWKRORJ\LV
UHTXLUHGSULRUWRHQUROOPHQW6OLGHVIURPWKHPRVWUHFHQWSUHUHJLVWUDWLRQELRSV\RUUHVHFWLRQ
PXVWEHVXEPLWWHGIRUUHYLHZLIWKHSUHYLRXVVXUJHU\ZDVQRWSHUIRUPHGDW1,+
:LWKLQGD\VSULRUWRUHJLVWUDWLRQWKHIROORZLQJDVVHVVPHQWVDUHUHTXLUHG
 $FRPSOHWHKLVWRU\DQGQHXURORJLFDOH[DPLQDWLRQWRLQFOXGHGRFXPHQWDWLRQRIWKHSDWLHQW¶V
.DUQRIVN\3HUIRUPDQFH6WDWXV
 9LWDOVLJQVEORRGSUHVVXUH
 1HXURLPDJLQJFRQILUPLQJWXPRUSURJUHVVLRQVKDOOEHSHUIRUPHGRQDOOSDWLHQWV05,LV
SUHIHUUHGRYHU&7VFDQ
 OHDG(&*
 /DERUDWRU\(YDOXDWLRQ
D &%&ZLWKGLIIHUHQWLDOSODWHOHWV37377,15
E 7RWDOSURWHLQDOEXPLQFDOFLXPSKRVSKRUXVPDJQHVLXPJOXFRVH%81FUHDWLQLQH
VRGLXPSRWDVVLXPDONDOLQHSKRVSKDWDVH$/7$67WRWDOELOLUXELQGLUHFWELOLUXELQ
F 8ULQHRUVHUXPȕ+&*
 (FKRFDUGLRJUDP
 $VVHVVPHQWRIFRQFRPLWDQWPHGLFDWLRQVDQGWUHDWPHQWV

5(*,675$7,21352&('85(6
$XWKRUL]HGVWDIIPXVWUHJLVWHUDQHOLJLEOHFDQGLGDWHZLWK1&,&HQWUDO5HJLVWUDWLRQ2IILFH&52
ZLWKLQKRXUVRIVLJQLQJFRQVHQW$UHJLVWUDWLRQ(OLJLELOLW\&KHFNOLVWIURPWKHZHEVLWH
KWWSKRPHFFUFDQFHUJRYLQWUDHOLJLELOLW\ZHOFRPHKWPPXVWEHFRPSOHWHGDQGVHQWYLD
HQFU\SWHGHPDLOWR1&,&HQWUDO5HJLVWUDWLRQ2IILFHQFLFHQWUDOUHJLVWUDWLRQO#PDLOQLKJRY
$IWHUFRQILUPDWLRQRIHOLJLELOLW\DW&HQWUDO5HJLVWUDWLRQ2IILFH&52VWDIIZLOOFDOOSKDUPDF\WR
DGYLVHWKHPRIWKHDFFHSWDQFHRIWKHSDWLHQWRQWKHSURWRFROSULRUWRWKHUHOHDVHRIDQ\
LQYHVWLJDWLRQDODJHQWV9HULILFDWLRQRI5HJLVWUDWLRQZLOOEHIRUZDUGHGHOHFWURQLFDOO\YLDHPDLO
WRWKHUHVHDUFKWHDP$UHFRUGHULVDYDLODEOHGXULQJQRQZRUNLQJKRXUV
 7UHDWPHQW$VVLJQPHQW3URFHGXUHV
&RKRUWV


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

1XPEHU 1DPH
'HVFULSWLRQ

3ULPDU\*OLRVDUFRPD
3DWLHQWVZLWKSULPDU\JOLRVDUFRPD

6HFRQGDU\*OLRVDUFRPD
3DWLHQWVZLWKVHFRQGDU\JOLRVDUFRPD

3ULPDU\&16VDUFRPD
3DWLHQWVZLWKSULPDU\&16VDUFRPD

$UPV
1XPEHU 1DPH
'HVFULSWLRQ

([SHULPHQWDOWKHUDS\
6XQLWLQLEPJZLWK$FWL*UDSK

$UP$VVLJQPHQW
3DWLHQWVLQFRKRUWVDQGZLOOEHDVVLJQHGWRDUP

%$6(/,1((9$/8$7,21
$OOEDVHOLQHHYDOXDWLRQSURFHGXUHVVKRXOGEHGRQHSULRUWRWKHVWXG\WUHDWPHQWV7KH\GRQRW
QHHGWREHUHSHDWHGLISHUIRUPHGZLWKLQGD\VSULRUWRVWXG\GUXJLQLWLDWLRQ
x $FRPSOHWHKLVWRU\DQGSK\VLFDO>LQFOXGLQJEDVHOLQHEORRGSUHVVXUHPHDVXUHPHQWDQG
GHWHUPLQDWLRQRI.DUQRIVN\3HUIRUPDQFH6FRUH.36@H[DPLQDWLRQ
x $EDVHOLQHVWDQGDUG12%*G'37$HQKDQFHG05,VKRXOGEHSHUIRUPHG
x 7K\URLG)XQFWLRQ7HVWVDQGVXEVHTXHQWO\HYHU\F\FOHV
x 8ULQDO\VLV
x 0'$6,%7
x &RUUHODWLYH6WXGLHV%ORRG&ROOHFWLRQ
7KH0'$6,%7ZLOOEHFRPSOHWHGRQO\E\WKHSDWLHQWXQOHVVFKDQJHVLQYLVLRQRUZHDNQHVV
PDNHWKLVGLIILFXOW,IWKLVRFFXUVWKHQWKHFDUHJLYHURUUHVHDUFKDVVLVWDQWPD\UHDGWKHTXHVWLRQV
WRWKHSDWLHQWRUDVVLVWZLWKPDUNLQJWKHVHYHULW\QXPEHURUVFRUHDVGHVFULEHGE\WKHSDWLHQW$
FDUHJLYHUPD\FRPSOHWHWKHTXHVWLRQQDLUHVDVDSDWLHQWSUR[\LIWKHSDWLHQW¶VGHILFLWVSUHFOXGH
VHOIUHSRUWKRZHYHUWKLVPXVWEHGRQHDWHYHU\DVVHVVPHQWIURPEDVHOLQHWRHQGRIWUHDWPHQW
1RQ(QJOLVKVSHDNLQJSDWLHQWVZLOOFRPSOHWHWKHTXHVWLRQQDLUHZLWKWKHDVVLVWDQFHRIDQ
LQWHUSUHWHUGXULQJWKHFOLQLFYLVLW



$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH


678'<,03/(0(17$7,21

678'<'(6,*1
7KLVLVDSURVSHFWLYHVLQJOHLQVWLWXWLRQVLQJOHDUPPXOWLFRKRUWSKDVH,,VWXG\RIVXQLWLQLELQ
VXEMHFWVZLWKUHFXUUHQWJOLRVDUFRPDDQGSULPDU\&16VDUFRPDWKDWKDYHIDLOHGSULRUVXUJHU\
DQGLUUDGLDWLRQXQOHVVUDGLDWLRQWKHUDS\ZDVFRQWUDLQGLFDWHG6XEMHFWVZLOOEHFODVVLILHGLQWR
WKUHHFRKRUWV3ULPDU\JOLRVDUFRPD6HFRQGDU\JOLRVDUFRPD3ULPDU\&16VDUFRPD
&RKRUWH[SDQVLRQZLOOEHFDUULHGRXWDWLQGLFDWLRQRISURPLVLQJUHVSRQVH

 2SWLRQDO$VVHVVPHQWRI)UHH/LYLQJ3K\VLFDO$FWLYLW\DQG6OHHS4XDOLW\
)UHHOLYLQJSK\VLFDODFWLYLW\DQGVOHHSTXDOLW\ZLOOEHTXDQWLILHGFRQWLQXRXVO\XVLQJDVPDOO
QRQLQYDVLYHSRUWDEOHZDWFKDFFHOHURPHWHU$FWLJUDSK,QF3HQVDFROD)/DWWKHVXEMHFW¶V
ZULVW2YHUDOOSK\VLFDODFWLYLW\OHYHOVGDLO\FKDQJHVVOHHSGXUDWLRQDQGHIILFLHQF\DPRXQWRI
WLPHVSHQWLQVHGHQWDU\PRGHUDWHYLJRURXVLQWHQVLW\FDWHJRULHVDQGHVWLPDWHGDFWLYLW\
DVVRFLDWHGHQHUJ\H[SHQGLWXUHVZLOOEHH[WUDFWHGXVLQJHVWDEOLVKHGSUHGLFWLYHHTXDWLRQV
3DWLHQWVZLOOEHDVNHGWRZHDUWKH$FWLJUDSKGHYLFHIRU&\FOHWKURXJK&\FOH7KHSDWLHQW
ZLOOEULQJWKH$FWLJUDSKGHYLFHWRHDFKSDWLHQWYLVLWWRKDYHWKHEDWWHU\FKDQJHG7KLVFDQEH
GRQHLQSHUVRQDWHDFKYLVLWRUYLDPDLO$Q\ODSVHVLQ$FWLJUDSKPRQLWRULQJGXHWRUHPRYDORI
WKHGHYLFHE\WKHSDWLHQWGHDGEDWWHU\RUDQ\XQIRUHVHHQVLWXDWLRQVZLOOQRWFRQVWLWXWHD
SURWRFROGHYLDWLRQ
 6DIHW\&RQVLGHUDWLRQV
$FFHOHURPHWHUV7KHVHVPDOOZDWFKOLNHPRQLWRUVPD\FDXVHVOLJKWGLVFRPIRUWWRVXEMHFWV1R
RWKHUNQRZQULVNVDUHDVVRFLDWHG
 'RVH/LPLWLQJ7R[LFLW\'/7
7R[LFLWLHVZLOOEHJUDGHGDFFRUGLQJWRWKH&RPPRQ7HUPLQRORJ\&ULWHULDIRU$GYHUVH(YHQWV
&7&$(9HUVLRQ7R[LFLWLHVWKDWRFFXUGXULQJ&\FOHZLOOEHHYDOXDWHGIRUGHWHUPLQDWLRQ
RI'/7

'58*$'0,1,675$7,21
6XQLWLQLEPJZLOOEHVHOIDGPLQLVWHUHGRUDOO\RQFHGDLO\RQDQRXWSDWLHQWEDVLV6XQLWLQLE
ZLOOEHDGPLQLVWHUHGDWDGRVHRIPJGDLO\IRUFRQVHFXWLYHZHHNVIROORZHGE\ZHHNRI
UHVW6WXGLHVLQSDWLHQWVZLWKPHWDVWDWLFUHQDOFHOOFDUFLQRPDVXQLWLQLEWROHUDELOLW\ZDVVXSHULRU
ZLWKWKHZHHNVRQDQGZHHNRIIFRPSDUHGWRZHHNVRQDQGZHHNVRII>@3DWLHQWV
VKRXOGEHLQVWUXFWHGWRVWRUHVXQLWLQLEDWURRPWHPSHUDWXUH3DWLHQWZLOOWDNHVXQLWLQLERQFH
GDLO\ZLWKRUZLWKRXWIRRGDVGHVLUHG3DWLHQWVVKRXOGGULQNSOHQW\RIZDWHURUWDNHUHK\GUDWLRQ
IOXLGVWRDYRLGGHK\GUDWLRQLIGLDUUKHDRFFXUV3DWLHQWVVKRXOGEHDOHUWHGWRWKHSRVVLELOLW\WKDW
VXQLWLQLEFDSVXOHVFDQFDXVHD\HOORZGLVFRORUDWLRQRIWKHVNLQRQGLUHFWFRQWDFW,IWKLVKDSSHQV
WKHSDWLHQWVKRXOGZDVKLPPHGLDWHO\ZLWKVRDSDQGZDWHU7K\URLGIXQFWLRQZLOOEHPRQLWRUHG
DWEDVHOLQHDQGDWHYHU\WZRF\FOHV'RVHUHGXFWLRQVWRPJDQGWKHQPJZLOOEH
SHUPLWWHGIRUSDWLHQWVH[SHULHQFLQJJUDGHRUVXQLWLQLEUHODWHGWR[LFLWLHV


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

%HFDXVHK\SHUWHQVLRQLVDNQRZQDQGSRWHQWLDOO\VHULRXVEXWUDUHDGYHUVHHYHQWDVVRFLDWHGZLWK
VXQLWLQLEWUHDWPHQWSDWLHQWVZLOOKDYHWKHLUEORRGSUHVVXUHPRQLWRUHGDQGUHFRUGHGDWEDVHOLQH
DQGZHHNO\GXULQJWUHDWPHQWLQFOXGLQJWKHZHHNVRIIWKHLQYHVWLJDWLRQDOGUXJHLWKHUDWWKH
GRFWRUV¶RIILFHRUXVLQJDQ\FDOLEUDWHGHOHFWURQLFGHYLFH
$OOVXEMHFWVZLOOEHHYDOXDWHGZLWKPDJQHWLFUHVRQDQFHLPDJLQJDWEDVHOLQHDQGDIWHUHYHU\
F\FOHVRIWUHDWPHQW3DWLHQWVZLOOFRQWLQXHWUHDWPHQWXQWLOWKHUHLVGLVHDVHSURJUHVVLRQRU
GHYHORSPHQWRILQWROHUDEOHVLGHHIIHFWV

'26(02',),&$7,216
'RVHUHGXFWLRQVWRPJDQGWKHQPJZLOOEHSHUPLWWHGIRUSDWLHQWVH[SHULHQFLQJJUDGH
RUVXQLWLQLEUHODWHGWR[LFLWLHV,IWUHDWPHQWLVGHOD\HGIRUPRUHWKDQZHHNVGXHWRWUHDWPHQW
DVVRFLDWHGWR[LFLW\WKHSDWLHQWZLOOEHGLVFRQWLQXHGIURPWUHDWPHQWDQGIROORZHGXQWLOGLVHDVH
SURJUHVVLRQ

3DWLHQWVPD\FRQWLQXHWRUHFHLYHWKHUDS\SURYLGHGWKHIROORZLQJFULWHULDDUHPHWRQGD\
RIHDFKF\FOH
R $1&[/
R 3ODWHOHWV[/
R 1RQKHPDWRORJLFDOWR[LFLW\UHFRYHUHGWRޒJUDGHRUWROHUDEOHJUDGHRU
EDVHOLQH
R 1RHYLGHQFHRISURJUHVVLYHGLVHDVH

:LWKGHYHORSPHQWRIDGYHUVHHYHQWVSRVVLEO\UHODWHGWRVXQLWLQLEGRVHUHGXFWLRQLV
SHUPLWWHGVHHJXLGHOLQHEHORZ,IDQDGYHUVHHYHQWLVQRWFRYHUHGE\WKHJXLGHOLQH
GRVHPD\EHUHGXFHGRUKHOGDWWKHGLVFUHWLRQRIWKHLQYHVWLJDWRUIRUWKHVXEMHFW¶VVDIHW\
6XEMHFWVZLWKDGYHUVHHYHQWVWKDWDUHPDQDJHDEOHZLWKVXSSRUWLYHWKHUDS\PD\QRW
UHTXLUHGRVHUHGXFWLRQVHJQDXVHDYRPLWLQJPD\EHWUHDWHGZLWKDQWLHPHWLFVGLDUUKHD
PD\EHWUHDWHGZLWKORSHUDPLGHDQGHOHFWURO\WHDEQRUPDOLWLHVPD\EHFRUUHFWHGZLWK
VXSSOHPHQWVUDWKHUWKDQE\GRVHUHGXFWLRQ

,IDSDWLHQWWDNHVRUPRUHRIVFKHGXOHGGRVHVGXULQJDF\FOHPLVVHGGRVHVZLOOQRW
EHUHSRUWHGDVGHYLDWLRQV,IWKHVWXG\WHDPLQVWUXFWVDSDWLHQWWRKROGWKHLQYHVWLJDWLRQDO
GUXJLWZLOOQRWEHFRQVLGHUHGDSURWRFROGHYLDWLRQ

,QFUHDVHLQ%3KDVEHHQUHSRUWHGZLWKXVHRIDQWL9(*)DJHQWV*XLGHOLQHVIRU
PDQDJHPHQW>@LVSURYLGHGLQ$SSHQGL[

 'RVH0RGLILFDWLRQ*XLGHOLQHVIRU6XQLWLQLE$VVRFLDWHG7R[LFLW\
(YHQW
$(*UDGHRU2EVHUYDWLRQ
'RVH0RGLILFDWLRQ
1HXWURSHQLD
*UDGHVDQG
*UDGH
0DLQWDLQGRVH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

(YHQW
$(*UDGHRU2EVHUYDWLRQ
'RVH0RGLILFDWLRQ
*UDGHޒDQG*UDGH
+ROGVXQLWLQLEXQWLO$1&WKHQUHGXFH
GRVHOHYHODQGUHVXPHWUHDWPHQW
*UDGH
+ROGVXQLWLQLEXQWLO$1&WKHQUHGXFH
GRVHOHYHODQGUHVXPHWUHDWPHQW
7KURPERF\WRSHQLD
*UDGH
0DLQWDLQGRVH
*UDGHV

+ROGVXQLWLQLEXQWLOSODWHOHWVWKHQUHGXFH
GRVHOHYHODQGUHVXPHWUHDWPHQW

)HYHURUIOXOLNH
V\PSWRPV
*UDGHV
0DLQWDLQGRVH
)DWLJXH
*UDGHVDQG
0DLQWDLQGRVH
*UDGHDQGVHYHUH*UDGH
DWLQYHVWLJDWRUGLVFUHWLRQ
+ROGVXQLWLQLEXQWLO*UDGHWKHQUHGXFHGRVH
OHYHODQGUHVXPHWUHDWPHQW
47FSURORQJDWLRQ
'RQRWXVH&7&$(
JUDGHV
ޓEXWޒPVHF
5HYLHZSDWLHQW¶VFRQFRPLWDQWPHGLFDWLRQVIRU47
LQWHUYDOSURORQJLQJDJHQWV&RUUHFWDQ\HOHFWURO\WH
DEQRUPDOLWLHV&RQWLQXHVXQLWLQLEDWFXUUHQWGRVH
OHYHO
PVHF
6WRSVXQLWLQLEDQGDQ\RWKHU47LQWHUYDOSURORQJLQJ
DJHQWVLPPHGLDWHO\&RUUHFWDQ\HOHFWURO\WH
DEQRUPDOLWLHVWKHQ
,IWKHUHLVDSODXVLEOHH[SODQDWLRQIRU$(RWKHUWKDQ
VXQLWLQLEWUHDWPHQWDQGWKHFRQWULEXWLQJIDFWRULV
UHPRYHGUHVXPHVXQLWLQLEDWFXUUHQWGRVHOHYHODIWHU
WKH47FUHWXUQVWRPVHF
,IVXQLWLQLEPD\KDYHFRQWULEXWHGWRWKH$(5HGXFH
GRVHOHYHOVDQGUHVWDUWVXQLWLQLE
,I47FUHPDLQVޒPVHFDIWHUGD\VDWUHGXFHG
GRVHLQFUHDVHRQHGRVHOHYHODQGFRQWLQXHVXQLWLQLE
+DQGIRRWV\QGURPH *UDGHVDQG
0DLQWDLQGRVH
*UDGH
+ROGVXQLWLQLEXQWLOJUDGHWKHQUHVXPH
WUHDWPHQWDWVDPHGRVHRUUHGXFHGRVHOHYHODWWKH
GLVFUHWLRQRIWKHSK\VLFLDQ
*UDGHVDQG
0DLQWDLQGRVH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

(YHQW
$(*UDGHRU2EVHUYDWLRQ
'RVH0RGLILFDWLRQ
$67DQGRU$/7
HOHYDWLRQ
*UDGHVDQG
6XQLWLQLEVKRXOGEHGRVHGHOD\HGLIHOHYDWLRQRI
$/7LVޓ[8/1$67LVޓ[8/1DQGRU
ELOLUXELQLVޓ[8/1
6XQLWLQLEPD\EHUHDGPLQLVWHUHGZKHQOHYHOVRI
$/7DQG$67DUH[8/1DQGELOLUXELQLV[
8/16XQLWLQLEVKRXOGQRWEHUHDGPLQLVWHUHGLI
VXEMHFWVGHYHORSJUDGHKHSDWLFIDLOXUH
&7&$(YGHILQLWLRQ
3DWLHQWVPXVWKDYH/)7VFKHFNHGDWEDVHOLQHDQG
GXULQJHDFKWUHDWPHQWF\FOH/)7VVKRXOGEH
REWDLQHGDWDQ\WLPHZKHQWKH\DUHFOLQLFDOO\
LQGLFDWHG

 6XSSRUWLYH&DUH*XLGHOLQHV
x 1DXVHD9RPLWLQJ7UHDWDVQHHGHGDQGFRQVLGHULQLWLDWLRQRISURSK\ODFWLFDQWLHPHWLF
WKHUDS\3OHDVHQRWH2QGDQVHWURQDQGUHODWHGGUXJVDUHQRWUHFRPPHQGHGVLQFHWKH\
PD\LQWHUIHUHZLWKWKHPHWDEROLVPRIVXQLWLQLE2QGDQVHWURQPD\FRQWULEXWHWR47
LQWHUYDOSURORQJDWLRQ$SUHSLWDQWLVDPRGHUDWH&<3$LQKLELWRUVWKDWVKRXOGEH
DYRLGHGLISRVVLEOHRUXVHGZLWKFDXWLRQ
x 'LDUUKHD0DQDJHZLWKORSHUDPLGHDVQHHGHGPD[LPXP PJSHUGD\
x +DQGIRRWV\QGURPH7UHDWZLWKWRSLFDOHPROOLHQWVHJ$TXDSKRUWRSLFDOVWHURLGV
DQGRUDQWLKLVWDPLQHV9LWDPLQ%S\ULGR[LQHPJRUDOSHUGD\PD\DOVREH
XVHG

48(67,211$,5(6
7KH0'$6,%7ZLOOEHXWLOL]HGIRUWKLVSRUWLRQRIWKHVWXG\7KHLQVWUXPHQWZLOOEH
DGPLQLVWHUHGDWEDVHOLQHDQGWKHQDWWKHWLPHRIHDFKHYDOXDWLRQWKDWDOVRLQFOXGHVLPDJLQJ2I
QRWHWKH0'$6,%7ZLOOQHHGWREHJLYHQSULRUWRLQIRUPLQJWKHSDWLHQWVDERXWWKHUHVXOWVRI
WKHLPDJLQJVWXG\)XOOLQVWUXPHQWVDUHSURYLGHGLQWKH$SSHQGL[,QDGGLWLRQLQIRUPDWLRQ
UHJDUGLQJGHPRJUDSKLFVDQGWUHDWPHQWKLVWRU\ZLOOEHFROOHFWHGDVSDUWRIWKHODUJHUVWXG\DQG
XVHGLQWKLVDQDO\VLV
7KH0'$6,%7FRQVLVWVRIV\PSWRPVUDWHGRQDQSRLQWVFDOHWRWRLQGLFDWHWKH
SUHVHQFHDQGVHYHULW\RIWKHV\PSWRPZLWKEHLQJ³QRWSUHVHQW´DQGEHLQJ³DVEDGDV\RX
FDQLPDJLQH´(DFKV\PSWRPLVUDWHGDWLWVZRUVWLQWKHODVWKRXUV6\PSWRPVLQFOXGHGRQWKH
LQVWUXPHQWLQFOXGHWKRVHFRPPRQO\DVVRFLDWHGZLWKFDQFHUWKHUDSLHVDQGWKRVHDVVRFLDWHGZLWK
WKHXQGHUO\LQJGLVHDVH7KHTXHVWLRQQDLUHDOVRLQFOXGHVUDWLQJVRIKRZPXFKV\PSWRPV
LQWHUIHUHGZLWKGLIIHUHQWDVSHFWVRIDSDWLHQW¶VOLIHLQWKHODVWKRXUV7KHVHLQWHUIHUHQFHLWHPV
LQFOXGHJHQHUDODFWLYLW\PRRGZRUNLQFOXGHVERWKZRUNRXWVLGHWKHKRPHDQGKRXVHZRUN
UHODWLRQVZLWKRWKHUSHRSOHZDONLQJDQGHQMR\PHQWRIOLIH7KHLQWHUIHUHQFHLWHPVDUHDOVR
PHDVXUHGRQVFDOHV7KHDYHUDJHWLPHWRFRPSOHWHWKHLQVWUXPHQWLVPLQXWHV7KH
0'$6,%7KDVEHHQWUDQVODWHGLQWRODQJXDJHVEXWWKH(QJOLVKODQJXDJHYHUVLRQZLOOEH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

XVHGIRUWKLVVWXG\>@1RQ(QJOLVKVSHDNLQJSDWLHQWVZLOOFRPSOHWHWKHTXHVWLRQQDLUHZLWKWKH
DVVLVWDQFHRIDQLQWHUSUHWHUGXULQJWKHFOLQLFYLVLW


678'<&$/(1'$5

3URFHGXUH
6FUHHQLQJ
%DVHOLQH
&\FOH
6XEVHTXHQW&\FOHV
(QGRI
WUHDWPHQW
9LVLW
3RVW
7KHUDS\
)ROORZ
XS
'D\

'D\


'D\

'D\
'D\







+LVWRU\DQG
3(
;
;
;

;

;

9LWDOVLJQV
;
;
;

;

;

3HUIRUPDQFH
6FRUH.36
;
;
;

;

;
;
&%&ZGLII
SOWV
;
;
;

;

;

6HUXP
FKHPLVWU\
;
;
;

;

;

8ULQDO\VLV
;







37377,15
;







7K\URLG
IXQFWLRQWHVWV

;



;

;

ȕ+&*
VHUXPRU
XULQH
;







%ORRG
3UHVVXUH
;
;
;
;
;
;
;

&RUUHODWLYH
5HVHDUFK
6WXGLHV

;
;

;

;

0'$6,%7
;





;

&UDQLDO
05,&7
;





;

(.*(&+2
;







$GYHUVH
(YHQWV

;







&RQFRPLWDQW
0HGLFDWLRQV
;
;


;



$FWLJUDSK\
;
;
;
;
;
;


1,+
$GYDQFHG
;









$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

3URFHGXUH
6FUHHQLQJ
%DVHOLQH
&\FOH
6XEVHTXHQW&\FOHV
(QGRI
WUHDWPHQW
9LVLW
3RVW
7KHUDS\
)ROORZ
XS
'D\

'D\


'D\

'D\
'D\
'LUHFWLYHV
)RUP
7RWDOSURWHLQDOEXPLQFDOFLXPSKRVSKRUXVPDJQHVLXPJOXFRVH%81FUHDWLQLQHVRGLXP
SRWDVVLXPDONDOLQHSKRVSKDWDVH$/7$67WRWDOELOLUXELQGLUHFWELOLUXELQ
7K\URLGIXQFWLRQWHVWVWREHGRQHDWEDVHOLQH&''RIHYHU\RWKHUF\FOHDQGDWHQGRI
WUHDWPHQWYLVLW
%ORRGIRUFRUUHODWLYHVWXGLHVZLOOEHFROOHFWHGDW&'&'&'DQGDWHQGRIWUHDWPHQW
YLVLW
0'$6,%7WREHGRQHDWEDVHOLQHDWWLPHRILPDJLQJVWXGLHVWKURXJKRXWWUHDWPHQWDQGDWHQG
RIWUHDWPHQWYLVLW
5HVSRQVHDVVHVVPHQWWREHGRQHHYHU\RWKHUF\FOHZLWKLQGD\VRILQLWLDWLRQRIRGGQXPEHUHG
F\FOHVVWDUWLQJZLWK&\FOHDQGDWHQGRIWUHDWPHQWYLVLW3UH&05,LVGRQHDWVFUHHQLQJ
05,LVSUHIHUUHG
(&+2WREHGRQHDWVFUHHQLQJGD\RIF\FOHDQGHYHU\RWKHUF\FOH(.*(&+2IUHTXHQF\
RIGD\RIWKHWKLUGF\FOHDQGHYHU\RWKHUF\FOH
$GYHUVH(YHQWDQG&RQFRPLWDQW0HGLFDWLRQHYDOXDWLRQVWREHGRFXPHQWHGDWGD\RIHDFK
F\FOHDQGDWHQGRIWUHDWPHQWYLVLW
$FWL*UDSK\WREHGRQHDWEDVHOLQHDQGGXULQJF\FOHVWKURXJK
(QGRIWUHDWPHQWYLVLWZLOORFFXUDSSUR[LPDWHO\GD\VDIWHUWKHODVWGRVHRIVWXG\GUXJ,IWKH
SDWLHQWFDQQRWUHWXUQWRWKH&OLQLFDO&HQWHUIRUWKLVYLVLWDUHTXHVWZLOOEHPDGHWRFROOHFW
UHTXLUHGFOLQLFDOODEVIURPDORFDOSK\VLFLDQRUODERUDWRU\,IWKLVLVQRWSRVVLEOHSDWLHQWVPD\
EHDVVHVVHGE\WHOHSKRQHIRUV\PSWRPV
$VLQGLFDWHGLQVHFWLRQDOOVXEMHFWVDJHZLOOEHRIIHUHGWKHRSSRUWXQLW\WRFRPSOHWH
DQ1,+DGYDQFHGGLUHFWLYHVIRUP7KLVVKRXOGEHGRQHSUHIHUDEO\DWEDVHOLQHEXWFDQEHGRQH
DWDQ\WLPHGXULQJWKHVWXG\DVORQJDVWKHFDSDFLW\WRGRVRLVUHWDLQHG7KHFRPSOHWLRQRIWKH
IRUPLVVWURQJO\UHFRPPHQGHGEXWLVQRWUHTXLUHG

&5,7(5,$)255(029$/)52035272&2/7+(5$3<$1'2))678'<&5,7(5,$
3DWLHQWVPD\EHUHPRYHGIURPWKHSURWRFROWKHUDS\DQGRUVWXG\DWDQ\WLPHDWWKHLURZQUHTXHVW
RUPD\EHZLWKGUDZQDWWKHGLVFUHWLRQRIWKHLQYHVWLJDWRUIRUVDIHW\EHKDYLRUDORUDGPLQLVWUDWLYH
UHDVRQV
3ULRUWRUHPRYDOIURPVWXG\HIIRUWPXVWEHPDGHWRKDYHDOOVXEMHFWVFRPSOHWHDVDIHW\YLVLW
DSSUR[LPDWHO\GD\VIROORZLQJWKHODVWGRVHRIVWXG\WKHUDS\7KHIROORZLQJHYDOXDWLRQZLOO
RFFXU
x .36
x $GYHUVH(YHQWDVVHVVPHQW
x 3K\VLFDOH[DPLQDWLRQ
x 9LWDOVLJQVDQGZHLJKW
x &%&ZLWKGLIIHUHQWLDOFRPSUHKHQVLYHFKHPLVWU\SDQHOWK\URLGIXQFWLRQWHVWV


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

x &UDQLDOLPDJLQJ
x %ORRGFROOHFWLRQIRUFRUUHODWLYHVWXGLHV
x 0'$6,%7
 &ULWHULDIRU5HPRYDOIURP3URWRFRO7KHUDS\
7KHUHDVRQVIRUGLVFRQWLQXDWLRQPXVWEHFOHDUO\GRFXPHQWHGDQGPD\LQFOXGH
x 3DWLHQWYROXQWDULO\ZLWKGUDZVIURPWUHDWPHQWIROORZXSSHUPLWWHG
x &RPSOHWLRQRISURWRFROWKHUDS\
x 3URJUHVVLYHGLVHDVH
x 8QDFFHSWDEOHWR[LFLW\DVGHILQHGLQVHFWLRQ
x ,QYHVWLJDWRUGLVFUHWLRQ
x 3RVLWLYHSUHJQDQF\WHVW
x 7UHDWPHQWLVGHOD\HGIRUPRUHWKDQZHHNVGXHWRWUHDWPHQWDVVRFLDWHGWR[LFLW\
 2II6WXG\&ULWHULD
x &RPSOHWHGVWXG\IROORZXSSHULRG
x 3DUWLFLSDQWUHTXHVWVWREHZLWKGUDZQIURPVWXG\QRIROORZXSSHUPLWWHG
x 'HDWK
 2II3URWRFRO7KHUDS\DQG2II6WXG\3URFHGXUH
$XWKRUL]HGVWDIIPXVWQRWLI\&HQWUDO5HJLVWUDWLRQ2IILFH&52ZKHQDVXEMHFWLVWDNHQRII
SURWRFROWKHUDS\DQGZKHQDVXEMHFWLVWDNHQRIIVWXG\$3DUWLFLSDQW6WDWXV8SGDWHV)RUPIURP
WKHZHEVLWHKWWSKRPHFFUFDQFHUJRYLQWUDHOLJLELOLW\ZHOFRPHKWPPDLQSDJHPXVWEH
FRPSOHWHGDQGVHQWYLDHQFU\SWHGHPDLOWR1&,&HQWUDO5HJLVWUDWLRQ2IILFH
QFLFHQWUDOUHJLVWUDWLRQO#PDLOQLKJRY


&21&20,7$170(',&$7,2160($685(6
x $OOSUHVFULSWLRQDQGRYHUWKHFRXQWHUPHGLFDWLRQVDWWULDOHQWU\DVZHOODVDQ\QHZ
PHGLFDWLRQVVWDUWHGGXULQJWKHWULDOPXVWEHGRFXPHQWHG3DWLHQWPD\XVHDQ\RQJRLQJ
PHGLFDWLRQVQRWSURKLELWHGE\WKHSURWRFRO
x 1RRWKHUDQWLFDQFHUWKHUDS\DJHQWVDUHSHUPLWWHGZKLOHWKHSDWLHQWLVRQWKLVWULDO
x &RUWLFRVWHURLGVLQGXFHURI&<3$PD\EHXVHGIRUFRQWURORIVLJQDQGV\PSWRPVRI
LQFUHDVHGLQWUDFUDQLDOSUHVVXUHDQGPXVWEHUHFRUGHG,IWKHGRVHLVLQFUHDVHGGXULQJWKH
SHULRGRIGD\VEHIRUHVFKHGXOHGFUDQLDOLPDJLQJWKHVWXG\VKRXOGEHGHOD\HGE\DW
OHDVWZHHNV
x 8VHRIGUXJVZLWKSRWHQWLDOSURDUUK\WKPLFDFWLRQVVKRXOGQRWEHXVHG


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

x 6XQLWLQLELVSULPDULO\PHWDEROL]HGE\OLYHUHQ]\PHVLQSDUWLFXODU&<3$3DWLHQWV
PXVWQRWKDYHWDNHQSRWHQWLQKLELWRUVD]ROHDQWLIXQJDOVVXFKDV
NHWRFRQD]ROHLWUDFRQD]ROHFODULWKURP\FLQHU\WKURP\FLQGLOWLD]HPYHUDSDPLORU
LQGXFHUVULIDPSLQULIDEXWLQFDUEDPD]HSLQHSKHQREDUELWDOSKHQ\WRLQ6W-RKQ¶VZRUW
RI&<3$HQ]\PHZLWKLQDQGGD\VSULRUWRGUXJDGPLQLVWUDWLRQUHVSHFWLYHO\
$OVRGXULQJWKHVWXG\SRWHQWLQKLELWRUVDQGLQGXFHUVVKRXOGQRWEHDGPLQLVWHUHG,I
XVDJHLVQHFHVVDU\WKLVPXVWEHGLVFXVVHGZLWKDVWXG\WHDPPHPEHUDQGRXWFRPHRIWKH
GLVFXVVLRQVKRXOGEHGRFXPHQWHG
x $SUHSLWDQWJUDSHIUXLWMXLFHIOXFRQD]ROHDQGYRULFRQD]ROHDUHPRGHUDWH&<3$
LQKLELWRUVWKDWVKRXOGEHDYRLGHGLISRVVLEOHRUXVHGZLWKFDXWLRQ
x 2QGDQVHWURQDQGUHODWHGGUXJVDUHQRWUHFRPPHQGHGVLQFHWKH\PD\LQWHUIHUHZLWKWKH
PHWDEROLVPRIVXQLWLQLE
x 'UXJVNQRZQWRFDXVHSURORQJDWLRQRI47FVKRXOGEHDYRLGHG


%,263(&,0(1&2//(&7,21

&255(/$7,9(678',(6)255(6($5&+

7HVWDVVD\
9ROXPHEORRG
DSSUR[
7\SHRI
WXEH
&ROOHFWLRQ
SRLQW
KUV
/RFDWLRQRI
VSHFLPHQ
DQDO\VLV
&LUFXODWLQJ
PDWXUH
HQGRWKHOLDOFHOOV
DQGHQGRWKHOLDO
SURJHQLWRUFHOOV
,PPXQH
PRQLWRULQJ
PODW&'&'
&'
&37FLWUDWH
EOXHEODFN
&'&'
&'DQGDW
HQGRIWUHDWPHQW
YLVLW
7UHSHO/DE
&LUFXODWLQJWXPRU
FHOOV
PODW&'
&'&'
&HOO6DYH
WXEH
&'&'
&'DQGDW
HQGRIWUHDWPHQW
YLVLW
7UHSHO/DE
,PPXQHVXEVHW
DQDO\VHV
PODW&'&'
&'
&37FLWUDWH
EOXHEODFN
&'&'
&'DQGDW
HQGRIWUHDWPHQW
YLVLW
7UHSHO/DE

)RU7UHSHO/DEVDPSOHVFRQWDFWWKHODEE\HPDLO-DQH7UHSHO1HFNHUVWUHSHO#KHOL[QLKJRY
6XQPLQ/HHOHHVXQ#PDLOQLKJRY0LQ-XQJ/HHOHHPLQ#PDLOQLKJRYDQG$NLUD<XQR


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

DNLUD\XQR#QLKJRYZKHQWKHSDWLHQWLVVFKHGXOHGDQGE\SKRQHDWZKHQWKH
EORRGKDVEHHQGUDZQDQGD7UHSHO/DEPHPEHUZLOOFRPHWRSLFNLWXS6WRUHDWDPELHQW
WHPSHUDWXUH7KHVDPSOHVZLOOEH'EDUFRGHGVHFXUHO\VWRUHGDWWKHDSSURSULDWHWHPSHUDWXUH
DQGHQWHUHGLQWRDVHFXUHSDWLHQWGDWDEDVHWKDWFDQRQO\EHDFFHVVHGE\ODERUDWRU\
PHPEHUV(DFKODERUDWRU\PHPEHUFDQRQO\LQWHUDFWZLWKWKHGDWDEDVHDWWKHLUDSSURYHGOHYHO
RIDFFHVV$OOODERUDWRU\PHPEHUVKDYHFRPSOHWHGFRXUVHVLQSDWLHQWLQIRUPDWLRQVHFXULW\DQG
FRPSXWHUVHFXULW\6DPSOHVZLOORQO\EHUHOHDVHGZLWKDSSURYDORIWKH3ULQFLSDO,QYHVWLJDWRU
1RFHOOOLQHVZLOOEHHVWDEOLVKHG

6$03/(6725$*(75$&.,1*$1'',6326,7,21
6DPSOHVZLOOEHRUGHUHGLQ&5,6DQGWUDFNHGWKURXJKD&OLQLFDO7ULDO'DWD0DQDJHPHQWV\VWHP
6KRXOGD&5,6VFUHHQQRWEHDYDLODEOHWKH&5,6GRZQWLPHSURFHGXUHVZLOOEHIROORZHG
6DPSOHVZLOOQRWEHVHQWRXWVLGH1,+ZLWKRXW,5%QRWLILFDWLRQDQGDQH[HFXWHG07$
3DUDIILQHPEHGGHGWLVVXHEORFNVDQGXQVWDLQHGVOLGHVZLOOEHVWRUHGDW1&,/DERUDWRU\RI
3DWKRORJ\ORFDWHGDW%XLOGLQJ
$OOVSHFLPHQVREWDLQHGLQWKHSURWRFRODUHXVHGDVGHILQHGLQWKHSURWRFRO$Q\VSHFLPHQVWKDW
DUHUHPDLQLQJDWWKHFRPSOHWLRQRIWKHSURWRFROZLOOEHVWRUHGLQWKHFRQGLWLRQVGHVFULEHGDERYH
7KHVWXG\ZLOOUHPDLQRSHQVRORQJDVVDPSOHRUGDWDDQDO\VLVFRQWLQXHV6DPSOHVIURP
FRQVHQWLQJVXEMHFWVZLOOEHVWRUHGXQWLOWKH\DUHQRORQJHURIVFLHQWLILFYDOXHRULIDVXEMHFW
ZLWKGUDZVFRQVHQWIRUWKHLUFRQWLQXHGXVHDWZKLFKWLPHWKH\ZLOOEHGHVWUR\HG7KH3,ZLOO
UHSRUWDQ\ORVVRUGHVWUXFWLRQRIVDPSOHVWRWKH1&,,5%DVVRRQDVKHLVPDGHDZDUHRIVXFK
ORVV
,IWKHSDWLHQWZLWKGUDZVFRQVHQWWKHSDUWLFLSDQW¶VGDWDZLOOEHH[FOXGHGIURPIXWXUHGLVWULEXWLRQV
EXWGDWDWKDWKDYHDOUHDG\EHHQGLVWULEXWHGIRUDSSURYHGUHVHDUFKXVHZLOOQRWEHDEOHWREH
UHWULHYHG
7KH3,ZLOOUHSRUWGHVWUR\HGVDPSOHVWRWKH,5%LIVDPSOHVEHFRPHXQVDOYDJHDEOHEHFDXVHRI
HQYLURQPHQWDOIDFWRUVH[EURNHQIUHH]HURUODFNRIGU\LFHLQDVKLSSLQJFRQWDLQHURULID
SDWLHQWZLWKGUDZVFRQVHQW6DPSOHVZLOODOVREHUHSRUWHGDVORVWLIWKH\DUHORVWLQWUDQVLW
EHWZHHQIDFLOLWLHVRUPLVSODFHGE\DUHVHDUFKHU)UHH]HUSUREOHPVORVWVDPSOHVRURWKHU
SUREOHPVDVVRFLDWHGZLWKVDPSOHVZLOODOVREHUHSRUWHGWRWKH,5%WKH1&,&OLQLFDO'LUHFWRU
DQGWKHRIILFHRIWKH&&51&,

'$7$&2//(&7,21$1'(9$/8$7,21

'$7$&2//(&7,21
7KH3,ZLOOEHUHVSRQVLEOHIRURYHUVHHLQJHQWU\RIGDWDLQWRDQLQKRXVHSDVVZRUGSURWHFWHG
HOHFWURQLFV\VWHPDQGHQVXULQJGDWDDFFXUDF\FRQVLVWHQF\DQGWLPHOLQHVV'DWDZLOOEHHQWHUHG
LQWRWKH&''DWDEDVH7KH0'$6,%7UHVSRQVHVZLOOEHHQWHUHGE\VWXG\VXEMHFWVGLUHFWO\
LQWR/DEPDWUL[YLD6FULEH$FWLJUDSKGDWDZLOOEHGRZQORDGHGIURPWKHGHYLFHXVLQJ$FWL/LIH
6RIWZDUH7KHSULQFLSDOLQYHVWLJDWRUDVVRFLDWHLQYHVWLJDWRUVUHVHDUFKQXUVHVDQGRUDFRQWUDFWHG
GDWDPDQDJHUZLOODVVLVWZLWKWKHGDWDPDQDJHPHQWHIIRUWV$OOGDWDREWDLQHGGXULQJWKHFRQGXFW
RIWKHSURWRFROZLOOEHNHSWLQVHFXUHQHWZRUNGULYHVRULQDSSURYHGDOWHUQDWLYHVLWHVWKDWFRPSO\


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

ZLWK1,+VHFXULW\VWDQGDUGV3ULPDU\DQGILQDODQDO\]HGGDWDZLOOKDYHLGHQWLILHUVVRWKDW
UHVHDUFKGDWDFDQEHDWWULEXWHGWRDQLQGLYLGXDOKXPDQVXEMHFWSDUWLFLSDQW
$OODGYHUVHHYHQWVLQFOXGLQJFOLQLFDOO\VLJQLILFDQWDEQRUPDOILQGLQJVRQODERUDWRU\HYDOXDWLRQV
UHJDUGOHVVRIVHYHULW\ZLOOEHIROORZHGXQWLOUHWXUQWREDVHOLQHRUVWDELOL]DWLRQRIHYHQW3DWLHQWV
ZLOOEHIROORZHGIRUDGYHUVHHYHQWVIRUGD\VDIWHUUHPRYDOIURPVWXG\WUHDWPHQWRUXQWLORII
VWXG\ZKLFKHYHUFRPHVILUVW
$QDEQRUPDOODERUDWRU\YDOXHZLOOEHFRQVLGHUHGDQ$(LIWKHODERUDWRU\DEQRUPDOLW\LV
FKDUDFWHUL]HGE\DQ\RIWKHIROORZLQJ
x
5HVXOWVLQGLVFRQWLQXDWLRQIURPWKHVWXG\
x
,VDVVRFLDWHGZLWKFOLQLFDOVLJQVRUV\PSWRPV
x
5HTXLUHVWUHDWPHQWRUDQ\RWKHUWKHUDSHXWLFLQWHUYHQWLRQ
x
,VDVVRFLDWHGZLWKGHDWKRUDQRWKHUVHULRXVDGYHUVHHYHQWLQFOXGLQJKRVSLWDOL]DWLRQ
x
,VMXGJHGE\WKH,QYHVWLJDWRUWREHRIVLJQLILFDQWFOLQLFDOLPSDFW
x
,IDQ\DEQRUPDOODERUDWRU\UHVXOWLVFRQVLGHUHGFOLQLFDOO\VLJQLILFDQWWKHLQYHVWLJDWRUZLOO
SURYLGHGHWDLOVDERXWWKHDFWLRQWDNHQZLWKUHVSHFWWRWKHWHVWGUXJDQGDERXWWKHSDWLHQW¶V
RXWFRPH

(QGRIVWXG\SURFHGXUHV'DWDZLOOEHVWRUHGDFFRUGLQJWR++6)'$UHJXODWLRQVDQG1,+
,QWUDPXUDO5HFRUGV5HWHQWLRQ6FKHGXOHDVDSSOLFDEOH
/RVVRUGHVWUXFWLRQRIGDWD6KRXOGZHEHFRPHDZDUHWKDWDPDMRUEUHDFKLQRXUSODQWR
SURWHFWVXEMHFWFRQILGHQWLDOLW\DQGWULDOGDWDKDVRFFXUUHGWKH,5%ZLOOEHQRWLILHG

'$7$6+$5,1*3/$16
 +XPDQ'DWD6KDULQJ3ODQ
:KDWGDWDZLOOEHVKDUHG"
,ZLOOVKDUHKXPDQGDWDJHQHUDWHGLQWKLVUHVHDUFKIRUIXWXUHUHVHDUFKDVIROORZV
BB;B'HLGHQWLILHGGDWDLQDQ1,+IXQGHGRUDSSURYHGSXEOLFUHSRVLWRU\
BB;B'HLGHQWLILHGGDWDLQ%75,6DXWRPDWLFIRUDFWLYLWLHVLQWKH&OLQLFDO&HQWHU
BB;B'HLGHQWLILHGRULGHQWLILHGGDWDZLWKDSSURYHGRXWVLGHFROODERUDWRUVXQGHUDSSURSULDWH
DJUHHPHQWV

+RZDQGZKHUHZLOOWKHGDWDEHVKDUHG"
'DWDZLOOEHVKDUHGWKURXJK
B;BB$Q1,+IXQGHGRUDSSURYHGSXEOLFUHSRVLWRU\,QVHUWQDPHRUQDPHV&OLQLFDOWULDOVJRY
B;BB%75,6DXWRPDWLFIRUDFWLYLWLHVLQWKH&OLQLFDO&HQWHU
B;BB$SSURYHGRXWVLGHFROODERUDWRUVXQGHUDSSURSULDWHLQGLYLGXDODJUHHPHQWV
B;BB3XEOLFDWLRQDQGRUSXEOLFSUHVHQWDWLRQV



$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

:KHQZLOOWKHGDWDEHVKDUHG"
B;BB%HIRUHSXEOLFDWLRQ
B;BB$WWKHWLPHRISXEOLFDWLRQRUVKRUWO\WKHUHDIWHU

5(63216(&5,7(5,$
 'HILQLWLRQV
(YDOXDEOHIRUWR[LFLW\$OOSDWLHQWVZLOOEHHYDOXDEOHIRUWR[LFLW\IURPWKHWLPHRIWKHLUILUVW
WUHDWPHQWZLWKVXQLWLQLE
(YDOXDEOHIRUREMHFWLYHUHVSRQVH2QO\WKRVHSDWLHQWVZKRKDYHPHDVXUDEOHGLVHDVHSUHVHQWDW
EDVHOLQHKDYHUHFHLYHGDWOHDVWRQHF\FOHRIWKHUDS\DQGKDYHKDGWKHLUGLVHDVHUHHYDOXDWHG
ZLOOEHFRQVLGHUHGHYDOXDEOHIRUUHVSRQVH7KHVHSDWLHQWVZLOOKDYHWKHLUUHVSRQVHFODVVLILHG
DFFRUGLQJWRWKHGHILQLWLRQVVWDWHGEHORZ1RWH3DWLHQWVZKRH[KLELWREMHFWLYHGLVHDVH
SURJUHVVLRQSULRUWRWKHHQGRIF\FOHZLOODOVREHFRQVLGHUHGHYDOXDEOH
(YDOXDEOH1RQ7DUJHW'LVHDVH5HVSRQVH3DWLHQWVZKRKDYHOHVLRQVSUHVHQWDWEDVHOLQHWKDWDUH
HYDOXDEOHEXWGRQRWPHHWWKHGHILQLWLRQVRIPHDVXUDEOHGLVHDVHKDYHUHFHLYHGDWOHDVWRQHF\FOH
RIWKHUDS\DQGKDYHKDGWKHLUGLVHDVHUHHYDOXDWHGZLOOEHFRQVLGHUHGHYDOXDEOHIRUQRQWDUJHW
GLVHDVH7KHUHVSRQVHDVVHVVPHQWLVEDVHGRQWKHSUHVHQFHDEVHQFHRUXQHTXLYRFDOSURJUHVVLRQ
RIWKHOHVLRQV
 'LVHDVH3DUDPHWHUV
0HDVXUDEOHGLVHDVH%DVHGRQ5$12FULWHULD>@
 5$12&ULWHULDIRU5HVSRQVH

5$12&ULWHULDIRU5HVSRQVH





&5
35
6'
3'
7JDGROLQLXPHQKDQFLQJGLVHDVH
1RQH
Ļ
ĻEXW
Ĺ
Ĺ
7)/$,5
6WDEOHRUĻ
6WDEOHRUĻ
6WDEOHRUĻ
Ĺ
1HZOHVLRQ
1RQH
1RQH
1RQH
3UHVHQW

&RUWLFRVWHURLGV
1RQH
6WDEOHRUĻ
6WDEOHRUĻ
QD
&OLQLFDOVWDWXV
6WDEOHRUĹ
6WDEOHRUĹ
6WDEOHRUĹ
Ļ
5HTXLUHPHQWIRUUHVSRQVH
$OO
$OO
$OO
$Q\

3URJUHVVLRQRFFXUVZKHQWKLVFULWHULRQLVSUHVHQW
,QFUHDVHLQFRUWLFRVWHURLGVDORQHZLOOQRWEHWDNHQLQWRDFFRXQWLQGHWHUPLQLQJSURJUHVVLRQLQWKH
DEVHQFHRISHUVLVWHQWFOLQLFDOGHWHULRUDWLRQ
Ļ GHFUHDVHGĹ LQFUHDVHG
&5 FRPSOHWHUHVSRQVH35 SDUWLDOUHVSRQVH6' VWDEOHGLVHDVH3' SURJUHVVLYHGLVHDVH,I3'LV
XQFOHDUEDVHGRQZKLWHPDWWHUFKDQJHVSDWLHQWVPD\EHNHSWRQWULDO
)/$,5IOXLGDWWHQXDWHGLQYHUVLRQUHFRYHU\1$QRWDSSOLFDEOH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH


 (YDOXDWLRQRI%HVW2YHUDOO5HVSRQVH
 'XUDWLRQRIRYHUDOOUHVSRQVH7KHGXUDWLRQRIRYHUDOOUHVSRQVHLVPHDVXUHGIURPWKH
WLPHPHDVXUHPHQWFULWHULDDUHPHWIRU&5RU35ZKLFKHYHULVILUVWUHFRUGHGXQWLOWKH
ILUVWGDWHWKDWUHFXUUHQWRUSURJUHVVLYHGLVHDVHLVREMHFWLYHO\GRFXPHQWHGWDNLQJDV
UHIHUHQFHIRUSURJUHVVLYHGLVHDVHWKHVPDOOHVWPHDVXUHPHQWVUHFRUGHGVLQFHWKH
WUHDWPHQWVWDUWHG
 7KHGXUDWLRQRIRYHUDOO&5GXUDWLRQRIRYHUDOO&5LVPHDVXUHGIURPWKHWLPH
PHDVXUHPHQWFULWHULDDUHILUVWPHWIRU&5XQWLOWKHILUVWGDWHWKDWSURJUHVVLYHGLVHDVHLV
REMHFWLYHO\GRFXPHQWHG
 'XUDWLRQRIVWDEOHGLVHDVH6WDEOHGLVHDVHLVPHDVXUHGIURPWKHVWDUWRIWKHWUHDWPHQW
XQWLOWKHFULWHULDIRUSURJUHVVLRQDUHPHWWDNLQJDVUHIHUHQFHWKHVPDOOHVWPHDVXUHPHQWV
UHFRUGHGVLQFHWKHWUHDWPHQWVWDUWHGLQFOXGLQJWKHEDVHOLQHPHDVXUHPHQWV
 3URJUHVVLRQ)UHH6XUYLYDO
3)6LVGHILQHGDVWKHGXUDWLRQRIWLPHIURPVWDUWRIWUHDWPHQWWRWLPHRISURJUHVVLRQRUGHDWK
ZKLFKHYHURFFXUVILUVW,QFDVHVZKHUHWKLVPLJKWEHXQFOHDUSDWLHQWVPD\FRQWLQXHRQWULDO
 5HVSRQVH5HYLHZ
$OOVXEMHFWVZLOOEHHYDOXDWHGE\FUDQLDOLPDJLQJHYHU\ZHHNV

72;,&,7<&5,7(5,$
7KHIROORZLQJDGYHUVHHYHQWPDQDJHPHQWJXLGHOLQHVDUHLQWHQGHGWRHQVXUHWKHVDIHW\RIHDFK
SDWLHQWZKLOHRQWKHVWXG\7KHGHVFULSWLRQVDQGJUDGLQJVFDOHVIRXQGLQWKHUHYLVHG1&,
&RPPRQ7HUPLQRORJ\&ULWHULDIRU$GYHUVH(YHQWV&7&$(YHUVLRQZLOOEHXWLOL]HGIRU$(
UHSRUWLQJ$OODSSURSULDWHWUHDWPHQWDUHDVVKRXOGKDYHDFFHVVWRDFRS\RIWKH&7&$(YHUVLRQ
$FRS\RIWKH&7&$(YHUVLRQFDQEHGRZQORDGHGIURPWKH&7(3ZHEVLWH
KWWSFWHSFDQFHUJRYSURWRFRO'HYHORSPHQWHOHFWURQLFBDSSOLFDWLRQVFWFKWP

6$)(7<5(3257,1*5(48,5(0(176'$7$$1'6$)(7<021,725,1*
3/$1

'(),1,7,216
 $GYHUVH(YHQW
$Q\XQWRZDUGPHGLFDORFFXUUHQFHLQDKXPDQVXEMHFWLQFOXGLQJDQ\DEQRUPDOVLJQIRU
H[DPSOHDEQRUPDOSK\VLFDOH[DPRUODERUDWRU\ILQGLQJV\PSWRPRUGLVHDVHWHPSRUDOO\
DVVRFLDWHGZLWKWKHVXEMHFW¶VSDUWLFLSDWLRQLQUHVHDUFKZKHWKHURUQRWFRQVLGHUHGUHODWHGWRWKH
VXEMHFW¶VSDUWLFLSDWLRQLQWKHUHVHDUFK
 6XVSHFWHGDGYHUVHUHDFWLRQ
6XVSHFWHGDGYHUVHUHDFWLRQPHDQVDQ\DGYHUVHHYHQWIRUZKLFKWKHUHLVDUHDVRQDEOHSRVVLELOLW\
WKDWWKHGUXJFDXVHGWKHDGYHUVHHYHQW)RUWKHSXUSRVHVRI,1'VDIHW\UHSRUWLQJµUHDVRQDEOH
SRVVLELOLW\¶PHDQVWKHUHLVHYLGHQFHWRVXJJHVWDFDXVDOUHODWLRQVKLSEHWZHHQWKHGUXJDQGWKH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

DGYHUVHHYHQW$VXVSHFWHGDGYHUVHUHDFWLRQLPSOLHVDOHVVHUGHJUHHRIFHUWDLQW\DERXWFDXVDOLW\
WKDQDGYHUVHUHDFWLRQZKLFKPHDQVDQ\DGYHUVHHYHQWFDXVHGE\DGUXJ
 8QH[SHFWHGDGYHUVHUHDFWLRQ
$QDGYHUVHHYHQWRUVXVSHFWHGDGYHUVHUHDFWLRQLVFRQVLGHUHG³XQH[SHFWHG´LILWLVQRWOLVWHGLQ
WKHLQYHVWLJDWRUEURFKXUHRULVQRWOLVWHGDWWKHVSHFLILFLW\RUVHYHULW\WKDWKDVEHHQREVHUYHGRU
LIDQLQYHVWLJDWRUEURFKXUHLVQRWUHTXLUHGRUDYDLODEOHLVQRWFRQVLVWHQWZLWKWKHULVN
LQIRUPDWLRQGHVFULEHGLQWKHJHQHUDOLQYHVWLJDWLRQDOSODQRUHOVHZKHUHLQWKHFXUUHQWDSSOLFDWLRQ
8QH[SHFWHG´DOVRUHIHUVWRDGYHUVHHYHQWVRUVXVSHFWHGDGYHUVHUHDFWLRQVWKDWDUHPHQWLRQHGLQ
WKHLQYHVWLJDWRUEURFKXUHDVRFFXUULQJZLWKDFODVVRIGUXJVRUDVDQWLFLSDWHGIURPWKH
SKDUPDFRORJLFDOSURSHUWLHVRIWKHGUXJEXWDUHQRWVSHFLILFDOO\PHQWLRQHGDVRFFXUULQJZLWKWKH
SDUWLFXODUGUXJXQGHULQYHVWLJDWLRQ
 6HULRXV
$Q8QDQWLFLSDWHG3UREOHPRU3URWRFRO'HYLDWLRQLVVHULRXVLILWPHHWVWKHGHILQLWLRQRID6HULRXV
$GYHUVH(YHQWRULILWFRPSURPLVHVWKHVDIHW\ZHOIDUHRUULJKWVRIVXEMHFWVRURWKHUV
 6HULRXV$GYHUVH(YHQW
$QDGYHUVHHYHQWRUVXVSHFWHGDGYHUVHUHDFWLRQLVFRQVLGHUHGVHULRXVLILQWKHYLHZRIWKH
LQYHVWLJDWRURUWKHVSRQVRULWUHVXOWVLQDQ\RIWKHIROORZLQJ
x
'HDWK
x
$OLIHWKUHDWHQLQJDGYHUVHGUXJH[SHULHQFH
x
,QSDWLHQWKRVSLWDOL]DWLRQRUSURORQJDWLRQRIH[LVWLQJKRVSLWDOL]DWLRQ
x
3HUVLVWHQWRUVLJQLILFDQWLQFDSDFLW\RUVXEVWDQWLDOGLVUXSWLRQRIWKHDELOLW\WRFRQGXFW
QRUPDOOLIHIXQFWLRQV
x
$FRQJHQLWDODQRPDO\ELUWKGHIHFW
x
,PSRUWDQWPHGLFDOHYHQWVWKDWPD\QRWUHVXOWLQGHDWKEHOLIHWKUHDWHQLQJRUUHTXLUH
KRVSLWDOL]DWLRQPD\EHFRQVLGHUHGDVHULRXVDGYHUVHGUXJH[SHULHQFHZKHQEDVHGXSRQ
DSSURSULDWHPHGLFDOMXGJPHQWWKH\PD\MHRSDUGL]HWKHSDWLHQWRUVXEMHFWDQGPD\
UHTXLUHPHGLFDORUVXUJLFDOLQWHUYHQWLRQWRSUHYHQWRQHRIWKHRXWFRPHVOLVWHGLQWKLV
GHILQLWLRQ
 'LVDELOLW\
$VXEVWDQWLDOGLVUXSWLRQRIDSHUVRQ¶VDELOLW\WRFRQGXFWQRUPDOOLIHIXQFWLRQV
 /LIHWKUHDWHQLQJDGYHUVHGUXJH[SHULHQFH
$Q\DGYHUVHHYHQWRUVXVSHFWHGDGYHUVHUHDFWLRQWKDWSODFHVWKHSDWLHQWRUVXEMHFWLQWKHYLHZRI
WKHLQYHVWLJDWRURUVSRQVRUDWLPPHGLDWHULVNRIGHDWKIURPWKHUHDFWLRQDVLWRFFXUUHGLHLW
GRHVQRWLQFOXGHDUHDFWLRQWKDWKDGLWRFFXUUHGLQDPRUHVHYHUHIRUPPLJKWKDYHFDXVHGGHDWK
 3URWRFRO'HYLDWLRQ1,+'HILQLWLRQ
$Q\FKDQJHGLYHUJHQFHRUGHSDUWXUHIURPWKH,5%DSSURYHGUHVHDUFKSURWRFRO


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 1RQFRPSOLDQFH1,+'HILQLWLRQ
7KHIDLOXUHWRFRPSO\ZLWKDSSOLFDEOH1,++XPDQ5HVHDUFK3URWHFWLRQV3URJUDP+533
SROLFLHV,5%UHTXLUHPHQWVRUUHJXODWRU\UHTXLUHPHQWVIRUWKHSURWHFWLRQRIKXPDQUHVHDUFK
VXEMHFWV
 8QDQWLFLSDWHG3UREOHP
$Q\LQFLGHQWH[SHULHQFHRURXWFRPHWKDW
x ,VXQH[SHFWHGLQWHUPVRIQDWXUHVHYHULW\RUIUHTXHQF\LQUHODWLRQWR
DWKHUHVHDUFKULVNVWKDWDUHGHVFULEHGLQWKH,5%DSSURYHGUHVHDUFKSURWRFRODQG
LQIRUPHGFRQVHQWGRFXPHQW,QYHVWLJDWRU¶V%URFKXUHRURWKHUVWXG\GRFXPHQWVDQG
EWKHFKDUDFWHULVWLFVRIWKHVXEMHFWSRSXODWLRQEHLQJVWXGLHG$1'
x ,VUHODWHGRUSRVVLEO\UHODWHGWRSDUWLFLSDWLRQLQWKHUHVHDUFK$1'
x 6XJJHVWVWKDWWKHUHVHDUFKSODFHVVXEMHFWVRURWKHUVDWDJUHDWHUULVNRIKDUPLQFOXGLQJ
SK\VLFDOSV\FKRORJLFDOHFRQRPLFRUVRFLDOKDUPWKDQZDVSUHYLRXVO\NQRZQRU
UHFRJQL]HG

1&,,5%$1'&/,1,&$/',5(&7255(3257,1*
 1&,,5%DQG1&,&'([SHGLWHG5HSRUWLQJRI8QDQWLFLSDWHG3UREOHPVDQG'HDWKV
7KH3URWRFRO3,ZLOOUHSRUWLQWKH1,+3UREOHP)RUPWRWKH1&,,5%DQG1&,&OLQLFDO
'LUHFWRU
x $OOGHDWKVH[FHSWGHDWKVGXHWRSURJUHVVLYHGLVHDVH
x $OO3URWRFRO'HYLDWLRQV
x $OO8QDQWLFLSDWHG3UREOHPV
x $OOQRQFRPSOLDQFH
5HSRUWVPXVWEHUHFHLYHGZLWKLQGD\VRI3,DZDUHQHVVYLDL5,6
 1&,,5%5HTXLUHPHQWVIRU3,5HSRUWLQJDW&RQWLQXLQJ5HYLHZ
7KHSURWRFRO3,ZLOOUHSRUWWRWKH1&,,5%
 $VXPPDU\RIDOOSURWRFROGHYLDWLRQVLQDWDEXODUIRUPDWWRLQFOXGHWKHGDWHWKH
GHYLDWLRQRFFXUUHGDEULHIGHVFULSWLRQRIWKHGHYLDWLRQDQGDQ\FRUUHFWLYHDFWLRQ
 $VXPPDU\RIDQ\LQVWDQFHVRIQRQFRPSOLDQFH
 $WDEXODUVXPPDU\RIWKHIROORZLQJDGYHUVHHYHQWV
x $OO*UDGHXQH[SHFWHGHYHQWVWKDWDUHSRVVLEO\SUREDEO\RUGHILQLWHO\UHODWHGWRWKH
UHVHDUFK
x $OO*UDGHDQGHYHQWVWKDWDUHSRVVLEO\SUREDEO\RUGHILQLWHO\UHODWHGWRWKH
UHVHDUFK
x $OO*UDGHHYHQWVUHJDUGOHVVRIDWWULEXWLRQ
x $OO6HULRXV(YHQWVUHJDUGOHVVRIDWWULEXWLRQ


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

127(*UDGHHYHQWVDUHQRWUHTXLUHGWREHUHSRUWHG

6$)(7<5(3257,1*&5,7(5,$727+(3+$50$&(87,&$/&2//$%25$7256
 5HSRUWLQJRI6HULRXV$GYHUVH(YHQWV
:LWKLQWZHQW\IRXUKRXUVRIILUVWDZDUHQHVVRIWKHHYHQWLPPHGLDWHO\LIWKHHYHQWLVIDWDO
RUOLIHWKUHDWHQLQJ3ULQFLSDO,QYHVWLJDWRUZLOOUHSRUWWR3IL]HUE\IDFVLPLOHDW
DQ\6HULRXV$GYHUVH(YHQW³6$(´6XFK6$(VDUHWREHUHSRUWHGIRU6WXG\VXEMHFWVZKR
DUHDVVLJQHGRULQGLYLGXDOVRWKHUZLVHH[SRVHGWRWKH3IL]HU3URGXFW3ULQFLSDO,QYHVWLJDWRU
VKRXOGUHSRUW6$(VDVVRRQDVWKH\DUHGHWHUPLQHGWRPHHWWKHGHILQLWLRQHYHQLIFRPSOHWH
LQIRUPDWLRQLVQRW\HWDYDLODEOH
 3UHJQDQF\([SRVXUHRU/DFNRI(IIHFW
(YHQWKRXJKWKHUHPD\QRWEHDQDVVRFLDWHG6$(H[SRVXUHWRWKH3IL]HU3URGXFWGXULQJ
SUHJQDQF\H[SRVXUHWRWKH3IL]HU3URGXFWGXULQJODFWDWLRQDQGRFFXSDWLRQDOH[SRVXUHWRWKH
3IL]HU3URGXFWDUHUHSRUWDEOHDQGODFNRIHIIHFWRIWKH3IL]HU3URGXFWPD\DOVREHUHSRUWDEOH
7KHWHUP6$(ZLOOEHXQGHUVWRRGWRLQFOXGHH[SRVXUHGXULQJSUHJQDQF\H[SRVXUHGXULQJ
ODFWDWLRQRFFXSDWLRQDOH[SRVXUHDQGUHSRUWDEOHLQVWDQFHVRIODFNRIHIIHFW
 +\¶V/DZ&DVHV
&DVHVRISRWHQWLDOGUXJLQGXFHGOLYHULQMXU\DVDVVHVVHGE\ODERUDWRU\WHVWYDOXHV³+\¶V/DZ
&DVHV´DUHDOVRUHSRUWDEOHWR3IL]HU,ID6WXG\VXEMHFWGHYHORSVDEQRUPDOYDOXHVLQDVSDUWDWH
DPLQRWUDQVIHUDVH³$67´RUDODQLQHDPLQRWUDQVIHUDVH³$/7´RUERWKFRQFXUUHQWZLWK
DEQRUPDOHOHYDWLRQVLQWRWDOELOLUXELQDQGQRRWKHUNQRZQFDXVHRIOLYHULQMXU\WKDWHYHQWZRXOG
EHFODVVLILHGDVD+\¶V/DZ&DVH7KHWHUP6$(ZLOOEHXQGHUVWRRGWRDOVRLQFOXGH+\¶V/DZ
&DVHV
 5HSRUWLQJ
 )RUPV
3ULQFLSDO,QYHVWLJDWRUZLOOUHSRUW6$(VXVLQJRQHRIWKHIROORZLQJIRUPVDUHSRUWLQJIRUP
DSSURYHGE\WKHORFDOUHJXODWRU\DXWKRULW\D&,206IRUPD3IL]HUSURYLGHG
,QYHVWLJDWRU,QLWLDWHG5HVHDUFK6HULRXV$GYHUVH(YHQW)RUPRUDQ\RWKHUIRUP
SURVSHFWLYHO\DSSURYHGE\3IL]HU7KH5HSRUWDEOH(YHQW)D[&RYHU6KHHWSURYLGHGE\3IL]HU
PXVWDOVREHLQFOXGHGZLWKHDFK6$(VXEPLWWHG
 6$(5HSRUWLQJ3HULRG
7KH6$(VWKDWDUHVXEMHFWWRWKLVUHSRUWLQJSURYLVLRQDUHWKRVHWKDWRFFXUIURPDIWHUWKHILUVW
GRVHRIWKH3IL]HU3URGXFWWKURXJKWZHQW\HLJKWFDOHQGDUGD\VDIWHUWKHODVWDGPLQLVWUDWLRQ
RIWKH3IL]HU3URGXFW,QDGGLWLRQLI3ULQFLSDO,QYHVWLJDWRUEHFRPHVDZDUHRIDQ6$(RFFXUULQJ
DQ\WLPHDIWHUWKHDGPLQLVWUDWLRQRIWKHODVWGRVHRIWKH3IL]HU3URGXFW3ULQFLSDO,QYHVWLJDWRU
VKRXOGUHSRUWWKDW6$(WR3IL]HULIWKH3ULQFLSDO,QYHVWLJDWRUVXVSHFWVDFDXVDOUHODWLRQVKLS
EHWZHHQWKH3IL]HU3URGXFWDQGWKH6$(
 ([FOXVLRQVIURP6$(5HSRUWLQJ5HTXLUHPHQWV
6SHFLILFDOO\H[FOXGHGIURPWKHUHSRUWLQJUHTXLUHPHQWVIRU6$(VXQGHUWKLVSURWRFROLVDQ\6$(
LGHQWLILHGLQWKH3URWRFRODVDQWLFLSDWHGWRRFFXULQWKH6WXG\SRSXODWLRQDWVRPHIUHTXHQF\
LQGHSHQGHQWRIGUXJH[SRVXUHXQOHVVWKH3ULQFLSDO,QYHVWLJDWRUDVVHVVHVVXFKDQHYHQWDVUHODWHG


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

WRWKH3IL]HU3URGXFW$OVRVSHFLILFDOO\H[FOXGHGIURPWKHUHSRUWLQJUHTXLUHPHQWVLVDQ\6$(
MXGJHGE\WKH3ULQFLSDO,QYHVWLJDWRUWRUHSUHVHQWSURJUHVVLRQRIWKHPDOLJQDQF\XQGHUVWXG\
XQOHVVLWUHVXOWVLQGHDWKZLWKLQWKH6$(5HSRUWLQJ3HULRG

'$7$$1'6$)(7<021,725,1*3/$1
 3ULQFLSDO,QYHVWLJDWRU5HVHDUFK7HDP
7KHFOLQLFDOUHVHDUFKWHDPZLOOPHHWRQDZHHNO\EDVLVZKHQSDWLHQWVDUHEHLQJDFWLYHO\WUHDWHG
RQWKHWULDOWRGLVFXVVHDFKSDWLHQW'HFLVLRQVDERXWGRVHOHYHOHQUROOPHQWDQGGRVHHVFDODWLRQLI
DSSOLFDEOHZLOOEHPDGHEDVHGRQWKHWR[LFLW\GDWDIURPSULRUSDWLHQWV
$OOGDWDZLOOEHFROOHFWHGLQDWLPHO\PDQQHUDQGUHYLHZHGE\WKHSULQFLSDOLQYHVWLJDWRURUDOHDG
DVVRFLDWHLQYHVWLJDWRU$GYHUVHHYHQWVZLOOEHUHSRUWHGDVUHTXLUHGDERYH$Q\VDIHW\FRQFHUQV
QHZLQIRUPDWLRQWKDWPLJKWDIIHFWHLWKHUWKHHWKLFDODQGRUVFLHQWLILFFRQGXFWRIWKHWULDORU
SURWRFROGHYLDWLRQVZLOOEHLPPHGLDWHO\UHSRUWHGWRWKH,5%XVLQJL5,6
7KHSULQFLSDOLQYHVWLJDWRUZLOOUHYLHZDGYHUVHHYHQWDQGUHVSRQVHGDWDRQHDFKSDWLHQWWRHQVXUH
VDIHW\DQGGDWDDFFXUDF\7KHSULQFLSDOLQYHVWLJDWRUZLOOSHUVRQDOO\FRQGXFWRUVXSHUYLVHWKH
LQYHVWLJDWLRQDQGSURYLGHDSSURSULDWHGHOHJDWLRQRIUHVSRQVLELOLWLHVWRRWKHUPHPEHUVRIWKH
UHVHDUFKVWDII

67$7,67,&$/&216,'(5$7,216

*(1(5$/$3352$&+
:HPRQLWRUWKH255XVLQJWKH%D\HVLDQRSWLPDOSKDVH%23GHVLJQ>@6SHFLILFDOO\OHW
݊GHQRWHWKHLQWHULPVDPSOHVL]HDQGܰGHQRWHWKHPD[LPXPVDPSOHVL]H/HW݌GHQRWHWKH255
DQGGHILQHWKHQXOOK\SRWKHVLVܪ଴: ݌൑0.2UHSUHVHQWLQJWKDWWKHWUHDWPHQWLVLQHIILFDFLRXV:H
ZLOOVWRSHQUROOLQJSDWLHQWVDQGFODLPWKDWWKHWUHDWPHQWLVQRWSURPLVLQJLI
ܲݎ(݌> 0.2 פ ݀ܽݐܽ) < ߣ(݊
ܰ)ఈ,
ZKHUHߣ DQGߙ DUHGHVLJQSDUDPHWHUVRSWLPL]HGWRPLQLPL]HWKHFKDQFHRILQFRUUHFWO\
FODLPLQJWKDWDQHIILFDFLRXVWUHDWPHQWLVQRWSURPLVLQJLHW\SH,,HUURUXQGHUWKHDOWHUQDWLYH
K\SRWKHVLVܪଵ: ݌= 0.4ZKLOHFRQWUROOLQJWKHW\SH,HUURUUDWHDWLHWKHFKDQFHRI
LQFRUUHFWO\FODLPLQJWKDWDQLQHIILFDFLRXVWUHDWPHQWLVSURPLVLQJLVQRPRUHWKDQ
$VVXPLQJD%HWDSULRUGLVWULEXWLRQIRU݌WKHDERYHGHFLVLRQUXOHFRUUHVSRQGVWRWKH
IROORZLQJVWRSSLQJERXQGDULHVDQG\LHOGVDVWDWLVWLFDOSRZHURIXQGHUܪଵ
7DEOH6WRSSLQJERXQGDULHV
SDWLHQWVWUHDWHG 6WRSLIUHVSRQVHV 






%DVHGRQ7DEOHZHSHUIRUPWKHLQWHULPDQGILQDODQDO\VLVZKHQWKHQXPEHURIHQUROOHG
SDWLHQWVUHDFKHVDQG,IWKHQXPEHURIUHVSRQVHVIDLOVWRH[FHHGWKHVWRSSLQJ
ERXQGDU\ZHZLOOVXVSHQGDFFUXDOLQVSHFWWKHHIILFDF\GDWDDQGPDNHWKHJRQRJRGHFLVLRQ
EDVHGRQERWKWKH255DQGRWKHUFOLQLFDOFRQVLGHUDWLRQVHJ3)6


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

%HORZDUHWKHRSHUDWLQJFKDUDFWHULVWLFVRIWKHGHVLJQEDVHGRQVLPXODWLRQVXVLQJWKH
%23ZHEDSSOLFDWLRQZKLFKLVDYDLODEOHDWKWWSZZZWULDOGHVLJQRUJ
255 (DUO\VWRSSLQJ &ODLPSURPLVLQJ 6DPSOHVL]H





















:HPRQLWRUWKHUDWHRI'RVH/LPLWLQJ7R[LFLW\'/7LQGHSHQGHQWO\IRUHDFKFRKRUWXVLQJWKH
IROORZLQJ%D\HVLDQUXOHVWRSHQUROOLQJSDWLHQWVWRDFRKRUWLI3U'/7!_GDWD!7KDW
LVZHZLOOVWRSHQUROOLQJSDWLHQWVWRDFRKRUWLIWKHGDWDLQGLFDWHWKDWWKHUHLVPRUHWKDQ
FKDQFHWKDWWKHWUXH'/7UDWHLVKLJKHUWKDQ7KLVSRVWHULRUSUREDELOLW\LVFDOFXODWHGEDVHG
RQWKHEHWDELQRPLDOPRGHO7KHGHFLVLRQUXOHJLYHVWKHIROORZLQJVWRSSLQJUXOHDVVXPLQJD
%HWDSULRUGLVWULEXWLRQIRU'/7UDWH
6WRSHQUROOLQJSWVLI>RISWVZLWK'/7@>RISWVHYDOXDWHG@DQG
%HORZDUHWKHRSHUDWLQJFKDUDFWHULVWLFVRIWKHWR[LFLW\PRQLWRULQJUXOH

7UXHWR[LFLW\UDWH






(DUO\VWRSSUREDELOLW\





$YHUDJHVDPSOHVL]H







6$03/(6,=(-867,),&$7,21
:LWKWKHPD[LPXPVDPSOHVL]HRISDWHQWVSHUFRKRUWWKHFRQILGHQFHLQWHUYDORIWKH
HVWLPDWHG255ZLOOQRWEHZLGHUWKDQLQHDFKGLUHFWLRQ$WWKHWZRVLGHGVLJQLILFDQFHOHYHO
RIZHKDYHSRZHUWRGHWHFWWKH255RIYHUVXV

67$7,67,&$/$1$/<6,6
6XPPDU\VWDWLVWLFVLQFOXGLQJPHDQVWDQGDUGGHYLDWLRQDQGFRQILGHQFHLQWHUYDOZLOOEH
XVHGWRGHVFULEHWKH255.DSODQ0HLHUFXUYHZLOOEHXVHGWRHVWLPDWHWKH3)6:HZLOO
FDOFXODWHPHDQVWDQGDUGGHYLDWLRQDQGFRQILGHQFHLQWHUYDORI3)6DQGPHGLDQ3)6
6DIHW\ZLOOEHDVVHVVHGE\UHSRUWLQJWKHJUDGHVRIWR[LFLW\DQGWKHW\SHRIWR[LFLW\REVHUYHGIRU
DOOSDWLHQWVDQGVXPPDUL]LQJGDWDXVLQJWKHGHVFULSWLYHVWDWLVWLFVLQFOXGLQJPHDQVWDQGDUG
GHYLDWLRQDQGFRQILGHQFHLQWHUYDOV


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

7UHDWPHQWHIIHFWRIVXQLWLQLEZLOOEHHYDOXDWHGXVLQJDGYDQFHG05,RIWKHEUDLQ3HUIXVLRQDQG
GLIIXVLRQEDVHG05,SDUDPHWHUVLQFOXGLQJEXWQRWUHVWULFWHGWREORRGYROXPHPHDQDQGPHGLDQ
$'&DQGVWUXFWXUDOYROXPHVZLOOEHDQDO\]HG5HVXOWVZLOOEHVXPPDUL]HGDQGPHDQDQG
PHGLDQYDOXHVDWGLIIHUHQWWLPHSRLQWVZLOOEHWDEXODWHG&KDQJHVLQVXFKSDUDPHWHUVZLOOEH
FKHFNHGIRUVWDWLVWLFDOVLJQLILFDQFHDQGFRUUHODWHGZLWKWKHGLVHDVHVWDWXV7KHUHODWLRQVKLS
EHWZHHQELRPDUNHUVDQGUHVSRQVHZLOOEHHYDOXDWHGXVLQJ6SHDUPDQFRUUHODWLRQDQGUHJUHVVLRQ
DQDO\VLVWKHOHYHOVRIELRPDUNHUVZLOOEHFRPSDUHGEHWZHHQUHVSRQGHUVDQGQRQUHVSRQGHUV
XVLQJDQH[DFW:LOFR[RQUDQNVXPWHVWDQGWWHVW

3$7,(175(3257('287&20(6
5HFHLYHG0'$6,%7IRUPVZLOOEHFKHFNHGYHUVXVWKHWLPLQJVFKHGXOHDQGFRQVLGHUHGDVYDOLG
LIWKH\IDOOZLWKLQGD\VRIWKHVFKHGXOHGDVVHVVPHQW&RPSOLDQFHUDWHVZLOOEHFDOFXODWHGDV
WKHQXPEHURIUHFHLYHGYDOLGIRUPVRYHUWKHQXPEHURIH[SHFWHGIRUPV'LIIHUHQFHVEHWZHHQ
JURXSVLQFRPSOLDQFHZLOOEHWHVWHGE\XVHRI)LVKHU¶VH[DFWWHVWDWHYHU\WLPHSRLQW
:HZLOOXVHGHVFULSWLYHVWDWLVWLFVWRGHVFULEHKRZSDWLHQWVUDWHV\PSWRPVHYHULW\DQG
LQWHUIHUHQFHZLWKIXQFWLRQDWHDFKWLPHSRLQW(UURUEDUJUDSKVIRUHDFKRIWKHV\PSWRPVZLOOEH
FRQVWUXFWHGDWHDFKWLPHSRLQW7KHSURSRUWLRQRISDWLHQWVUDWLQJWKHLUV\PSWRPVWREHRU
JUHDWHURQDVFDOHZLOODOVREHUHSRUWHG:HZLOOFRQVWUXFWLQGLYLGXDOSDWLHQWSURILOHVIRU
HDFKRIWKHVHOHFWHGV\PSWRPVWRGHVFULEHWKHLQGLYLGXDOSDWLHQWV¶SDWWHUQVRIFKDQJHRYHUWLPH
:HZLOOFDOFXODWHWKHPHDQV\PSWRPVHYHULW\DQGPHDQV\PSWRPLQWHUIHUHQFHDWWKHWLPHRI
FOLQLFDOHYDOXDWLRQ(VWLPDWHVRIGLIIHUHQFHVLQWKHPHDQV\PSWRPVHYHULW\DQGPHDQV\PSWRP
LQWHUIHUHQFHEHWZHHQUHVSRQGHUVDQGQRQUHVSRQGHUVZLOOEHHVWLPDWHGLQWKHLQWHQWWRWUHDW
SRSXODWLRQ$OOSDWLHQWVZLWKDWOHDVWRQHYDOLGTXHVWLRQQDLUHZLOOEHLQFOXGHGLQWKHDQDO\VHV
4XHVWLRQQDLUHVFRPSOHWHGDWVWXG\UHJLVWUDWLRQZLOOEHFRQVLGHUHGEDVHOLQH$OOTXHVWLRQQDLUH
GDWDUHFHLYHGDIWHUUDQGRPL]DWLRQZLOOEHXVHGLQWKHSULPDU\DQDO\VHV
'LIIHUHQFHVRIDWOHDVWSRLQWVZLOOEHFODVVLILHGDVWKHPLQLPXPFOLQLFDOO\PHDQLQJIXOFKDQJH
LQWKHV\PSWRPVHYHULW\DQGV\PSWRPLQWHUIHUHQFHPHDVXUHV)RUH[DPSOHDQLQFUHDVHRI
SRLQWVRUPRUHZRXOGPHDQDPRGHUDWHLPSURYHPHQWZKHUHDVDGHFUHDVHRISRLQWVRUPRUH
ZRXOGEHLQWHUSUHWHGDVPRGHUDWHZRUVHQLQJ)RULQGLYLGXDOV\PSWRPVDULVHLQDV\PSWRP
VFRUHPHDQVGHWHULRUDWLRQZKHUHDVDUHGXFHGVFRUHPHDQVLPSURYHPHQWRIWKHVSHFLILF
V\PSWRP

&2//$%25$7,9($*5((0(176

$*5((0(177<3(
6XQLWLQLELVSURYLGHGE\3IL]HU,QFXQGHUD&OLQLFDO7ULDOV$JUHHPHQW&7$&7$
HIIHFWLYHZKLFKKDVEHHQDPHQGHG&7$$PHQGPHQWHIIHFWLYH

 +80$168%-(&763527(&7,216
 5$7,21$/()2568%-(&76(/(&7,21
7KLVVWXG\ZDVGHVLJQHGWRLQFOXGHZRPHQDQGPLQRULWLHVEXWZDVQRWGHVLJQHGWRPHDVXUH
GLIIHUHQFHVRILQWHUYHQWLRQHIIHFWV0HQDQGZRPHQZLOOEHUHFUXLWHGZLWKQRSUHIHUHQFHWR
JHQGHU1RH[FOXVLRQWRWKLVVWXG\ZLOOEHEDVHGRQUDFH0LQRULWLHVZLOODFWLYHO\EHUHFUXLWHG
WRSDUWLFLSDWH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 3$57,&,3$7,212)&+,/'5(1
%HFDXVHVDIHW\RIVXQLWLQLEKDVQRWEHHQHVWDEOLVKHGLQFKLOGUHQVXEMHFWVOHVVWKDQ\HDUVRI
DJHDUHH[FOXGHG
 3$57,&,3$7,212):20(12)&+,/'%($5,1*327(17,$/
3UHJQDQWZRPHQDUHH[FOXGHGIURPWKLVVWXG\EHFDXVHVXQLWLQLEKDVSRWHQWLDOIRUWHUDWRJHQLFRU
DERUWLIDFLHQWHIIHFWV7KHHIIHFWVRIVXQLWLQLERQWKHGHYHORSLQJKXPDQIHWXVDUHXQNQRZQ)RU
WKLVUHDVRQDQGEHFDXVHDQWLDQJLRJHQLFDJHQWVDUHNQRZQWREHWHUDWRJHQLFZRPHQRIFKLOG
EHDULQJSRWHQWLDODQGPHQPXVWDJUHHWRXVHDGHTXDWHFRQWUDFHSWLRQKRUPRQDORUEDUULHU
PHWKRGRIELUWKFRQWURODEVWLQHQFHSULRUWRVWXG\HQWU\DQGIRUWKHGXUDWLRQRIVWXG\WUHDWPHQW
 3$57,&,3$7,21)25+,93$7,(176
3DWLHQWVZLWKNQRZQ+,9KLVWRU\RQFRPELQDWLRQDQWLUHWURYLUDOWKHUDS\DUHLQHOLJLEOHEHFDXVHRI
WKHSRWHQWLDOIRUSKDUPDFRNLQHWLFLQWHUDFWLRQVZLWKVXQLWLQLE,QDGGLWLRQWKHVHSDWLHQWVDUHDW
LQFUHDVHGULVNRIOHWKDOLQIHFWLRQVZKHQWUHDWHGZLWKPDUURZVXSSUHVVLYHWKHUDS\
 3$57,&,3$7,212)68%-(&7681$%/(72*,9(&216(17
$GXOWVXQDEOHWRJLYHFRQVHQWDUHH[FOXGHGIURPHQUROOLQJLQWKHSURWRFRO+RZHYHUUHFRQVHQW
PD\EHQHFHVVDU\DQGWKHUHLVDSRVVLELOLW\WKRXJKXQOLNHO\WKDWVXEMHFWVFRXOGEHFRPH
GHFLVLRQDOO\LPSDLUHG)RUWKLVUHDVRQDQGEHFDXVHWKHUHLVDSURVSHFWRIGLUHFWEHQHILWIURP
UHVHDUFKSDUWLFLSDWLRQ6HFWLRQDOOVXEMHFWVZLOOEHRIIHUHGWKHRSSRUWXQLW\WRILOOLQWKHLU
ZLVKHVIRUUHVHDUFKDQGFDUHDQGDVVLJQDVXEVWLWXWHGHFLVLRQPDNHURQWKH³1,+$GYDQFH
'LUHFWLYHIRU+HDOWK&DUHDQG0HGLFDO5HVHDUFK3DUWLFLSDWLRQ´IRUPVRWKDWDQRWKHUSHUVRQFDQ
PDNHGHFLVLRQVDERXWWKHLUPHGLFDOFDUHLQWKHHYHQWWKDWWKH\EHFRPHLQFDSDFLWDWHGRU
FRJQLWLYHO\LPSDLUHGGXULQJWKHFRXUVHRIWKHVWXG\1RWH7KH3,RU$,ZLOOFRQWDFWWKH1,+
$ELOLW\WR&RQVHQW$VVHVVPHQW7HDP$&$7IRUHYDOXDWLRQDVQHHGHGIRUWKHIROORZLQJDQ
LQGHSHQGHQWDVVHVVPHQWRIZKHWKHUDQLQGLYLGXDOKDVWKHFDSDFLW\WRSURYLGHFRQVHQWDVVLVWDQFH
LQLGHQWLI\LQJDQGDVVHVVLQJDQDSSURSULDWHVXUURJDWHZKHQLQGLFDWHGDQGRUDQDVVHVVPHQWRI
WKHFDSDFLW\WRDSSRLQWDVXUURJDWH)RUWKRVHVXEMHFWVWKDWEHFRPHLQFDSDFLWDWHGDQGGRQRW
KDYHSUHGHWHUPLQHGVXEVWLWXWHGHFLVLRQPDNHUWKHSURFHGXUHVGHVFULEHGLQ0$63ROLF\
DQG1,++533623(IRUDSSRLQWLQJDVXUURJDWHGHFLVLRQPDNHUIRUDGXOWVXEMHFWVZKRDUH
DGHFLVLRQDOO\LPSDLUHGDQGEZKRGRQRWKDYHDOHJDOJXDUGLDQRUGXUDEOHSRZHURI
DWWRUQH\ZLOOEHIROORZHG
 (9$/8$7,212)%(1(),76$1'5,6.6',6&20)2576
7KHSULPDU\ULVNWRSDWLHQWVSDUWLFLSDWLQJLQWKLVUHVHDUFKVWXG\LVIURPWR[LFLW\RIVXQLWLQLEDV
GHVFULEHGLQWKHSURWRFRO
 $OWHUQDWLYH$SSURDFKHVRU7UHDWPHQWV
'XULQJWKHFRQVHQWLQJSURFHVVDOOULVNVSRWHQWLDOEHQHILWVWUHDWPHQWUHTXLUHPHQWVDQG
DOWHUQDWLYHWKHUDSHXWLFDSSURDFKHVWRSDUWLFLSDWLRQZLOOEHGLVFXVVHG
 3URFHGXUHIRU3URWHFWLQJ$JDLQVWRU0LQLPL]LQJ$Q\3RWHQWLDO5LVNV
$OOFDUHZLOOEHWDNHQWRPLQLPL]HVLGHHIIHFWVEXWWKH\FDQEHXQSUHGLFWDEOHLQQDWXUHDQG
VHYHULW\7KLVVWXG\PD\LQYROYHULVNVWRSDWLHQWVZKLFKDUHFXUUHQWO\XQIRUHVHHDEOH$OO


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

SDWLHQWVZLOOKDYHEORRGWHVWVH[DPLQDWLRQVDQGVFDQVDVGHVFULEHGLQWKHVWXG\FDOHQGDU
6HFWLRQ3DWLHQWVZLOODOVREHUHTXLUHGWRKDYHDORFDOSK\VLFLDQWRSURYLGHORQJWHUPFDUH
DQGWRPRQLWRUIRUFRPSOLFDWLRQV,ISDWLHQWVVXIIHUDQ\SK\VLFDOLQMXU\DVDUHVXOWRI
SDUWLFLSDWLRQLQWKLVVWXG\LPPHGLDWHPHGLFDOWUHDWPHQWLVDYDLODEOHDWWKH&OLQLFDO&HQWHU
1DWLRQDO&DQFHU,QVWLWXWH%HWKHVGD0DU\ODQG$OWKRXJKQRFRPSHQVDWLRQLVDYDLODEOHDQ\
LQMXU\ZLOOEHHYDOXDWHGDQGWUHDWHGLQNHHSLQJZLWKWKHEHQHILWVRUFDUHWRZKLFKSDWLHQWVDUH
HQWLWOHGXQGHUDSSOLFDEOHUHJXODWLRQV
 5,6.6%(1(),76$1$/<6,6
 %HQHILWV
7KHSRWHQWLDOEHQHILWWRDSDWLHQWRQWKLVVWXG\LVDUHGXFWLRQLQWKHVL]HRIWKHEUDLQWXPRU
ZKLFKPD\RUPD\QRWKDYHIDYRUDEOHLPSDFWRQV\PSWRPVDQGRUVXUYLYDO
 5LVNV
5LVNLQFOXGHVWR[LFLW\DVDUHVXOWRIDGPLQLVWHUHGVWXG\DJHQW)UHTXHQWPRQLWRULQJIRUDGYHUVH
HIIHFWVVKRXOGKHOSWRPLQLPL]HWKHULVNVDVVRFLDWHGZLWKDGPLQLVWUDWLRQRIVXQLWLQLE
 5LVNV%HQHILWV$QDO\VLV
7KHSRWHQWLDOEHQHILWIURPWKLVWKHUDS\LVGLVHDVHVWDELOL]DWLRQRUWXPRUVKULQNDJHDQGD
UHGXFWLRQLQV\PSWRPVFDXVHGE\WKHEUDLQWXPRUVXFKDVQHXURORJLFDOGHILFLWVDQGKHDGDFKH
(YHQZLWKHIIRUWVWRPLQLPL]HULVNVSDUWLFLSDWLRQLQWKLVSURWRFROLQYROYHVJUHDWHUWKDQPLQLPDO
ULVNEXWSUHVHQWVWKHSRWHQWLDOIRUGLUHFWEHQHILWWRLQGLYLGXDOVXEMHFWV
 &216(17352&(66$1''2&80(17$7,21
$OOSDWLHQWVZKRDUHEHLQJFRQVLGHUHGIRUWKLVWULDOZLOOXQGHUJRLQIRUPHGFRQVHQWSULRUWREHLQJ
HQUROOHGRQWKHWULDO7KH3,RUDVVRFLDWHLQYHVWLJDWRUZLOOSHUIRUPWKHFRQVHQWLQJSURFHVV
3DWLHQWVDQGIDPLO\PHPEHUVZKHQDSSOLFDEOHZLOOEHDVNHGWRUHDGWKHFRQVHQWDQGZLOOEH
HQFRXUDJHGWRDVNTXHVWLRQV,WZLOOEHVWDWHGFOHDUO\WKDWSDUWLFLSDWLRQLQWKHUHVHDUFKVWXG\LV
YROXQWDU\DQGWKDWSDUWLFLSDQWVFDQZLWKGUDZIURPWKHVWXG\ZLWKRXWORVLQJEHQHILWVWKH\ZRXOG
RWKHUZLVHEHHQWLWOHGWR3DWLHQWVZLOOEHHQUROOHGDIWHUWKHFRQVHQWGRFXPHQWKDVEHHQVLJQHG
6HSDUDWHFRQVHQWVZLOOEHREWDLQHGIRUDQ\VXUJLFDOSURFHGXUHVSHUIRUPHG7KHLQIRUPHG
FRQVHQWSURFHVVZLOOEHGRFXPHQWHGLQWKHSDWLHQW¶VPHGLFDOUHFRUG
,IQHZVDIHW\LQIRUPDWLRQUHVXOWVLQVLJQLILFDQWFKDQJHVLQWKHULVNEHQHILWDVVHVVPHQWWKH
FRQVHQWIRUPZLOOEHUHYLHZHGDQGXSGDWHGDVQHFHVVDU\$OOVXEMHFWVLQFOXGLQJWKRVHDOUHDG\
EHLQJWUHDWHGZLOOEHLQIRUPHGRIWKHQHZLQIRUPDWLRQEHJLYHQDFRS\RIWKHUHYLVHGIRUPDQG
EHDVNHGWRJLYHWKHLUFRQVHQWWRFRQWLQXHLQWKHVWXG\
 ,QIRUPHG&RQVHQWRI1RQ(QJOLVK6SHDNLQJ6XEMHFWV
,IWKHUHLVDQXQH[SHFWHGHQUROOPHQWRIDUHVHDUFKSDUWLFLSDQWIRUZKRPWKHUHLVQRWUDQVODWHG
H[WDQW,5%DSSURYHGFRQVHQWGRFXPHQWWKHSULQFLSDOLQYHVWLJDWRUDQGRUWKRVHDXWKRUL]HGWR
REWDLQLQIRUPHGFRQVHQWZLOOXVHWKH6KRUW)RUP2UDO&RQVHQW3URFHVVDVGHVFULEHGLQ0$6
3ROLF\02+653623&)5E7KHVXPPDU\WKDWZLOOEHXVHGLVWKH
(QJOLVKYHUVLRQRIWKHH[WDQW,5%DSSURYHGFRQVHQWGRFXPHQW6LJQHGFRSLHVRIERWKWKH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

(QJOLVKYHUVLRQRIWKHFRQVHQWDQGWKHWUDQVODWHGVKRUWIRUPZLOOEHJLYHQWRWKHVXEMHFWRUWKHLU
OHJDOO\DXWKRUL]HGUHSUHVHQWDWLYHDQGWKHVLJQHGRULJLQDOZLOOEHILOHGLQWKHPHGLFDOUHFRUG
8QOHVVWKH3,LVIOXHQWLQWKHSURVSHFWLYHVXEMHFW¶VODQJXDJHDQLQWHUSUHWHUZLOOEHSUHVHQWWR
IDFLOLWDWHWKHFRQYHUVDWLRQXVLQJHLWKHUWKHORQJWUDQVODWHGIRUPRUWKHVKRUWIRUP3UHIHUDEO\
VRPHRQHZKRLVLQGHSHQGHQWRIWKHVXEMHFWLHQRWDIDPLO\PHPEHUZLOODVVLVWLQSUHVHQWLQJ
LQIRUPDWLRQDQGREWDLQLQJFRQVHQW:KHQHYHUSRVVLEOHLQWHUSUHWHUVZLOOEHSURYLGHGFRSLHVRI
WKHUHOHYDQWFRQVHQWGRFXPHQWVZHOOEHIRUHWKHFRQVHQWFRQYHUVDWLRQZLWKWKHVXEMHFWWR
KRXUVLISRVVLEOH
:HUHTXHVWSURVSHFWLYH,5%DSSURYDORIWKHXVHRIWKHVKRUWIRUPSURFHVVIRUQRQ(QJOLVK
VSHDNLQJVXEMHFWVDQGZLOOQRWLI\WKH,5%DWWKHWLPHRIFRQWLQXLQJUHYLHZRIWKHIUHTXHQF\RI
WKHXVHRIWKH6KRUW)RUP
 3+$50$&(87,&$/$1'0(',&$/'(9,&(,1)250$7,21
 5$7,21$/()25,1'(;(037,21
7KLVLQYHVWLJDWLRQRIVXQLWLQLEDPDUNHWHGGUXJLVH[HPSWIURPWKH,1'UHTXLUHPHQWVEHFDXVH
DOOWKHFULWHULDIRUDQH[HPSWLRQLQEDUHPHW
x
7KHGUXJSURGXFWLVODZIXOO\PDUNHWHGLQWKH8QLWHG6WDWHV
x
7KHLQYHVWLJDWLRQLVQRWLQWHQGHGWREHUHSRUWHGWR)'$DVDZHOOFRQWUROOHGVWXG\LQ
VXSSRUWRIDQHZLQGLFDWLRQDQGWKHUHLVQRLQWHQWWRXVHLWWRVXSSRUWDQ\RWKHU
VLJQLILFDQWFKDQJHLQWKHODEHOLQJRIWKHGUXJ
x
,QWKHFDVHRIDSUHVFULSWLRQGUXJWKHLQYHVWLJDWLRQLVQRWLQWHQGHGWRVXSSRUWD
VLJQLILFDQWFKDQJHLQWKHDGYHUWLVLQJIRUWKHGUXJ
x
7KHLQYHVWLJDWLRQGRHVQRWLQYROYHDURXWHRIDGPLQLVWUDWLRQGRVHSDWLHQWSRSXODWLRQRU
RWKHUIDFWRUWKDWVLJQLILFDQWO\LQFUHDVHVWKHULVNRUGHFUHDVHVWKHDFFHSWDELOLW\RIWKH
ULVNDVVRFLDWHGZLWKWKHXVHRIWKHGUXJSURGXFW&)5ELLL
x
7KHLQYHVWLJDWLRQLVFRQGXFWHGLQFRPSOLDQFHZLWKWKHUHTXLUHPHQWVIRUUHYLHZE\DQ
,5%&)5SDUWDQGZLWKWKHUHTXLUHPHQWVIRULQIRUPHGFRQVHQW&)5SDUW
x
7KHLQYHVWLJDWLRQLVFRQGXFWHGLQFRPSOLDQFHZLWKWKHUHTXLUHPHQWVRILHWKH
LQYHVWLJDWLRQLVQRWLQWHQGHGWRSURPRWHRUFRPPHUFLDOL]HWKHGUXJSURGXFW
 681,7,1,%0$/$7(687(17
6XQLWLQLELVDQRUDOPXOWLWDUJHWHGW\URVLQHNLQDVHLQKLELWRURI.,73'*)5V9(*)5V5(7
DQG)/7DSSURYHGPXOWLQDWLRQDOO\IRUWKHWUHDWPHQWRIJDVWURLQWHVWLQDOVWURPDOWXPRUDIWHU
GLVHDVHSURJUHVVLRQRQRULQWROHUDQFHWRLPDWLQLEDGYDQFHGUHQDOFHOOFDUFLQRPDDQG
XQUHVHFWDEOHZHOOGLIIHUHQWLDWHGPHWDVWDWLFSDQFUHDWLFQHXURHQGRFULQHWXPRUV1(7
 6RXUFH
6XQLWLQLEZLOOEHSURYLGHGE\3IL]HU,QFIURPFRPPHUFLDOVXSSO\
 7R[LFLW\
3OHDVHVHHSDFNDJHLQVHUWIRUDFRPSOHWHOLVWRIWR[LFLWLHV


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

,QRYHUVXEMHFWVZLWKVROLGPDOLJQDQWWXPRUVGLDUUKHDIDWLJXHQDXVHD
GHFUHDVHGDSSHWLWHYRPLWLQJSDOPDUSODQWDUHU\WKURG\VDHVWKHVLD
V\QGURPHK\SHUWHQVLRQVWRPDWLWLVG\VJHXVLDDQGPXFRVDO
LQIODPPDWLRQZHUHWKHPRVWFRPPRQO\UHSRUWHGWUHDWPHQWHPHUJHQWDGYHUVHHYHQWV
2YHUDOOH[SHULHQFHGWUHDWPHQWUHODWHG$(VRI*UDGHRUVHYHULW\*UDGHLQ
RIVXEMHFWV*UDGHDQGJUDGHLQDQGRIVXEMHFWVUHVSHFWLYHO\7KHPRVW
FRPPRQO\UHSRUWHGZHUHQHXWURSHQLDIDWLJXHWKURPERF\WRSHQLD
SDOPDUSODQWDUHU\WKURG\VDHVWKHVLDV\QGURPHGLDUUKHDK\SHUWHQVLRQDQG
DVWKHQLD1HXWURSHQLDIDWLJXHSDOPDUSODQWDUHU\WKURG\VDHVWKHVLD
V\QGURPHWKURPERF\WRSHQLDGLDUUKHDDQGK\SHUWHQVLRQZHUHWKH
PRVWFRPPRQO\UHSRUWHGWUHDWPHQWUHODWHG$(VRI*UDGHVHYHULW\1HXWURSHQLD
WKURPERF\WRSHQLDDQGDQHPLDZHUHWKHPRVWFRPPRQO\UHSRUWHGWUHDWPHQW
UHODWHG$(VRI*UDGHVHYHULW\3XOPRQDU\HPEROLVPFDUGLDFIDLOXUHGHDWKFHUHEUDO
KHPRUUKDJHUHQDOIDLOXUHP\RFDUGLDOLQIDUFWLRQKHSDWLFIDLOXUHJDVWURLQWHVWLQDOKHPRUUKDJH
PXOWLRUJDQIDLOXUHUHVSLUDWRU\IDLOXUHSQHXPRQLDVHSWLFVKRFNFDUGLDFDUUHVWVHSVLVVXGGHQ
GHDWKWXPRUKHPRUUKDJHDQGKHPRUUKDJHZHUHDPRQJWKH*UDGHWUHDWPHQWUHODWHG$(V
UHSRUWHGLQDWOHDVWVXEMHFWV
%R[HG:DUQLQJ
6XQLWLQLEKDVEHHQDVVRFLDWHGZLWKKHSDWRWR[LFLW\ZKLFKPD\UHVXOWLQOLYHUIDLOXUHRUGHDWK
/LYHUIDLOXUHKDVEHHQREVHUYHGLQFOLQLFDOWULDOV>@DQGSRVWPDUNHWLQJH[SHULHQFH
/LYHUIDLOXUHVLJQVLQFOXGHMDXQGLFHHOHYDWHGWUDQVDPLQDVHVDQGRUK\SHUELOLUXELQHPLDLQ
FRQMXQFWLRQZLWKHQFHSKDORSDWK\FRDJXORSDWK\DQGRUUHQDOIDLOXUH0RQLWRUOLYHUIXQFWLRQ
WHVWV$/7$67ELOLUXELQEHIRUHLQLWLDWLRQRIWUHDWPHQWGXULQJHDFKF\FOHRIWUHDWPHQWDQGDV
$EEUHYLDWHG7LWOH7DUJHWHG5[LQ$GYDQFHG1(7V9HUVLRQ'DWH&RQILGHQWLDO
FOLQLFDOO\LQGLFDWHG6XQLWLQLEVKRXOGEHLQWHUUXSWHGIRU*UDGHRUGUXJUHODWHGKHSDWLF
DGYHUVHHYHQWVDQGGLVFRQWLQXHGLIWKHUHLVQRUHVROXWLRQ'RQRWUHVWDUWVXQLWLQLELISDWLHQWV
VXEVHTXHQWO\H[SHULHQFHVHYHUHFKDQJHVLQOLYHUIXQFWLRQWHVWVRUKDYHRWKHUVLJQVDQG
V\PSWRPVRIOLYHUIDLOXUH6DIHW\LQSDWLHQWVZLWK$/7RU$67!î8/1RULIGXHWROLYHU
PHWDVWDVHV!î8/1KDVQRWEHHQHVWDEOLVKHG
 )RUPXODWLRQDQG3UHSDUDWLRQ
+DUG*HODWLQ&DSVXOHV
6XQLWLQLEFDSVXOHVFRQVLVWRIKDUGJHODWLQFDSVXOHVFRQWDLQLQJVXQLWLQLEHTXLYDOHQWWR
PJDQGPJVXQLWLQLEWRJHWKHUZLWKPDQQLWROFURVFDUPHOORVHVRGLXP
SRYLGRQHDQGPDJQHVLXPVWHDUDWH7KHFDSVXOHVPD\EHSULQWHGRUXQSULQWHGDQGDUHFRORU
FRGHGIRUSRWHQF\GLIIHUHQWLDWLRQDVGHVFULEHGLQWDEOHEHORZ


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH


&$368/(675(17+$1''(6&5,37,21
PJ
/LJKWJUH\6L]HKDUGJHODWLQFDSVXOH

PJ
6ZHGLVK2UDQJH6L]HKDUGJHODWLQFDSVXOH

PJ
6ZHGLVK2UDQJH&DUDPHO6L]HKDUGJHODWLQFDSVXOH
PJ
6WDQGDUG<HOORZ6L]HKDUGJHODWLQFDSVXOH
PJ
&DUDPHO6L]HKDUGJHODWLQFDSVXOH

PJFDSVXOHVWUHQJWKLVFRPPHUFLDOO\DYDLODEOHLQVRPHPDUNHWVVLQFHKRZHYHUWKLVVWUHQJWKKDVQRW
EHHQXVHGLQFOLQLFDOLQYHVWLJDWLRQV


 6WDELOLW\DQG6WRUDJH
7KHVXQLWLQLEFDSVXOHVDUHSDFNDJHGLQRSDTXHSODVWLFERWWOHVDQGVKRXOGEHVWRUHGDWFRQWUROOHG
URRPWHPSHUDWXUHWRq&
7KHFDSVXOHFRQWHQWVZKHQVSULQNOHGRQDSSOHVDXFHRU\RJXUWDUHVWDEOHIRUXSWR
PLQXWHVXQGHUFRQGLWLRQVRIDPELHQWOLJKWDQGWHPSHUDWXUH
6HOI$GPLQLVWHUHG6WXG\'UXJV3ROLF\
$OORUDOVHOIDGPLQLVWHUHGLQYHVWLJDWLRQDODJHQWVZLOOEHSURSHUO\DFFRXQWHGIRUKDQGOHGDQG
GLVSRVHGLQDFFRUGDQFHZLWKH[LVWLQJIHGHUDOUHJXODWLRQVDQGSULQFLSOHVRI*RRG&OLQLFDO
3UDFWLFH$OORUDOVWXG\GUXJVZLOOEHUHFRUGHGLQWKHSDWLHQWGLDULHVIRXQGLQ$SSHQGL[7KLV
ZLOOEHXVHGDVDPHPRU\DLGHIRUVXEMHFWV$FOLQLFDOUHVHDUFKWHDPPDLQWDLQVWKHSULPDU\
VRXUFHUHFRUG
 ,QFRPSDWLELOLWLHV
&RQFRPLWDQWDGPLQLVWUDWLRQRIVXQLWLQLEZLWKWKHVWURQJ&<3$LQKLELWRUNHWRFRQD]ROH
UHVXOWHGLQDDQGLQFUHDVHRIWKHFRPSOH[>VXQLWLQLESULPDU\DFWLYHPHWDEROLWH@
&PD[DQG$8&fYDOXHVUHVSHFWLYHO\DIWHUDVLQJOHGRVHRIVXQLWLQLELQKHDOWK\YROXQWHHUV
$GPLQLVWUDWLRQRIVXQLWLQLEZLWKVWURQJLQKLELWRUVRIWKH&<3$IDPLO\HJULWRQDYLU
LWUDFRQD]ROHHU\WKURP\FLQFODULWKURP\FLQJUDSHIUXLWMXLFHPD\LQFUHDVHVXQLWLQLE
FRQFHQWUDWLRQV&RQFRPLWDQWDGPLQLVWUDWLRQZLWKLQKLELWRUVVKRXOGWKHUHIRUHEHDYRLGHGRU
WKHVHOHFWLRQRIDQDOWHUQDWHFRQFRPLWDQWPHGLFDWLRQZLWKQRRUPLQLPDOSRWHQWLDOWRLQKLELW
&<3$VKRXOGEHFRQVLGHUHG,IWKLVLVQRWSRVVLEOHWKHGRVDJHRIVXQLWLQLEPD\QHHGWREH
UHGXFHG



$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 :*7;%7
7KHXVHRIWKHZ*7;%7IRULQYHVWLJDWLRQLQWKLVVWXG\LVH[HPSWIURP,'(UHJXODWLRQV
7KHZ*7;%7LVDOHJDOO\PDUNHWHGGHYLFHWKDWLVD)'$FOHDUHG&ODVV,,ZLWKLQWKH867KH
Z*7;%WLVLQWHQGHGIRUXVHLQDSSOLFDWLRQVZKHUHTXDQWLILDEOHPHDVXUHPHQWDQGVWRUDJHRI
SK\VLFDOPRYHPHQWLVGHVLUHG)RUWKLVVWXG\Z*7;%7ZLOOEHXVHGWRPHDVXUHDQGUHFRUG
SK\VLFDOPRYHPHQWDVVRFLDWHGZLWKGDLO\DFWLYLW\DQGVOHHSZKLFKLVLQDOLJQPHQWZLWKLWV
LQGLFDWLRQ
7KHZ*7;%7GRHVQRWPHHWWKHFULWHULDRIDVLJQLILFDQWULVNGHYLFH,WLVQRWLQWHQGHGDVDQ
LPSODQWQRUGRHVLWSUHVHQWDSRWHQWLDOIRUVHULRXVULVNWRWKHKHDOWKVDIHW\RUZHOIDUHRID
VXEMHFWSXUSRUWHGRUUHSUHVHQWHGWREHIRUDXVHLQVXSSRUWLQJRUVXVWDLQLQJKXPDQOLIHQRU
SUHVHQWVDSRWHQWLDOIRUVHULRXVULVNWRWKHKHDOWKVDIHW\RUZHOIDUHRIDVXEMHFWIRUDXVHRI
VXEVWDQWLDOLPSRUWDQFHLQGLDJQRVLQJFXULQJPLWLJDWLQJRUWUHDWLQJGLVHDVHRURWKHUZLVH
SUHYHQWLQJLPSDLUPHQWRIKXPDQKHDOWKQRUSUHVHQWVDSRWHQWLDOIRUVHULRXVULVNWRWKHKHDOWK
VDIHW\RUZHOIDUHRIDVXEMHFWRU,WGRHVQRWRWKHUZLVHSUHVHQWDSRWHQWLDOIRUVHULRXVULVNWR
WKHKHDOWKVDIHW\RUZHOIDUHRIDVXEMHFW
 3URGXFW'HVFULSWLRQ
7KHZ*7;%7DFWLYLW\PRQLWRUFRQWDLQVDD[LV0(06DFFHOHURPHWHUZLWKDG\QDPLFUDQJH
RI*$FFHOHUDWLRQGDWDDUHVDPSOHGE\DELWDQDORJWRGLJLWDOFRQYHUWHUDWXVHUVSHFLILHG
UDWHVUDQJLQJIURP+]WR+]DQGVWRUHGLQDUDZQRQILOWHUHGDFFXPXODWHGIRUPDWLQWKH
XQLWVRIJUDYLW\*¶V'DWDDUHVWRUHGGLUHFWO\LQWRDQRQYRODWLOHIODVKPHPRU\
 0DQXIDFWXUHU$FWL*UDSK
 'LPHQVLRQV[[FP
 :HLJKWJUDPV
 6RXUFH
$,VLQWKH'LDEHWHV(QGRFULQRORJ\DQG2EHVLW\%UDQFKRI1,''.ZLOOSURYLGHWKHDFWLJUDSK\
HTXLSPHQW
 6WRUDJH
,QRUGHUWRPD[LPL]HEDWWHU\OLIH$FWL*UDSKUHFRPPHQGVGHYLFHVEHVWRUHGLQDSDUWLDOO\FKDUJHG
VWDWH±EDWWHU\FDSDFLW\LVLGHDOLQORZDPELHQWWHPSHUDWXUHV7KHGHYLFHVKRXOGQHYHU
EHVWRUHGORZHUWKDQ&RUKLJKHUWKDQ&
 $GPLQLVWUDWLRQ
3DUWLFLSDQWVZLOOEHJLYHQDVPDOOSRUWDEOHSDJHUW\SHDQGZDWFKOLNHDFFHOHURPHWHUVWRZHDUDW
WKHKLSRUQRQGRPLQDQWZULVW


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 3UHFDXWLRQV
7KHUHDUHQRVLJQLILFDQWULVNVDVVRFLDWHGZLWKDFWLJUDSK\6RPHSDWLHQWVPD\ILQGLWDQ
LQFRQYHQLHQFHWRZHDUWKHGHYLFH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 5()(5(1&(6



+DQ6-HWDO&OLQLFDOFKDUDFWHULVWLFVDQGRXWFRPHVIRUDPRGHUQVHULHVRISULPDU\
JOLRVDUFRPDSDWLHQWV&DQFHUS

+DQ6-HWDO3ULPDU\JOLRVDUFRPDNH\FOLQLFDODQGSDWKRORJLFGLVWLQFWLRQVIURP
JOLREODVWRPDZLWKLPSOLFDWLRQVDVDXQLTXHRQFRORJLFHQWLW\-1HXURRQFRO
S

&DFKLD'HWDO3ULPDU\DQGVHFRQGDU\JOLRVDUFRPDVFOLQLFDOPROHFXODUDQGVXUYLYDO
FKDUDFWHULVWLFV-1HXURRQFROS

5HLV50HWDO0ROHFXODUFKDUDFWHUL]DWLRQRI3'*)5DOSKD3'*)$DQGF.,76&)
LQJOLRVDUFRPDV&HOO2QFROS

0F'RQDOG3$*XKDDQG-3URYLDV3ULPDU\LQWUDFUDQLDOILEURVDUFRPDZLWK
LQWUDWXPRUDOKHPRUUKDJHQHXURSDWKRORJLFDOGLDJQRVLVZLWKUHYLHZRIWKHOLWHUDWXUH-
1HXURRQFROS

3DW\QD6DQG*3HQJ'LVWULEXWLRQRIVXQLWLQLEDQGLWVDFWLYHPHWDEROLWHLQEUDLQDQG
VSLQDOFRUGWLVVXHIROORZLQJRUDORULQWUDYHQRXVDGPLQLVWUDWLRQLQURGHQWVDQGPRQNH\V
(MF6XSSOHPHQWVS

6]DOHN(HWDO7KHSHQHWUDWLRQRIVXQLWLQLEWKURXJKWKHEORRGEUDLQEDUULHUDIWHUWKH
DGPLQLVWUDWLRQRIFLSURIOR[DFLQ$FWD3RO3KDUPS

)LQNH-+HWDO6XQLWLQLEUHYHUVHVW\SHLPPXQHVXSSUHVVLRQDQGGHFUHDVHV7
UHJXODWRU\FHOOVLQUHQDOFHOOFDUFLQRPDSDWLHQWV&OLQ&DQFHU5HVS


.R-6HWDO6XQLWLQLEPHGLDWHVUHYHUVDORIP\HORLGGHULYHGVXSSUHVVRUFHOO
DFFXPXODWLRQLQUHQDOFHOOFDUFLQRPDSDWLHQWV&OLQ&DQFHU5HVS

)LQNH-HWDO0'6&DVDPHFKDQLVPRIWXPRUHVFDSHIURPVXQLWLQLEPHGLDWHGDQWL
DQJLRJHQLFWKHUDS\,QW,PPXQRSKDUPDFROS

.RED\DVKL0HWDO&KDQJHVLQSHULSKHUDOEORRGLPPXQHFHOOVWKHLUSURJQRVWLF
VLJQLILFDQFHLQPHWDVWDWLFUHQDOFHOOFDUFLQRPDSDWLHQWVWUHDWHGZLWKPROHFXODUWDUJHWHG
WKHUDS\0HG2QFROS

$UPVWURQJ76HWDO9DOLGDWLRQRIWKH0'$QGHUVRQ6\PSWRP,QYHQWRU\%UDLQ7XPRU
0RGXOH0'$6,%7-1HXURRQFROS

$WNLQVRQ%-HWDO&OLQLFDORXWFRPHVIRUSDWLHQWVZLWKPHWDVWDWLFUHQDOFHOOFDUFLQRPD
WUHDWHGZLWKDOWHUQDWLYHVXQLWLQLEVFKHGXOHV-8UROS

.RQGR7HWDO6XSHULRUWROHUDELOLW\RIDOWHUHGGRVLQJVFKHGXOHRIVXQLWLQLEZLWK
ZHHNVRQDQGZHHNRIILQSDWLHQWVZLWKPHWDVWDWLFUHQDOFHOOFDUFLQRPDFRPSDULVRQWR
VWDQGDUGGRVLQJVFKHGXOHRIZHHNVRQDQGZHHNVRII-SQ-&OLQ2QFRO
S


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH


%ULQGD%-HWDO$QWL9(*),QGXFHG+\SHUWHQVLRQD5HYLHZRI3DWKRSK\VLRORJ\DQG
7UHDWPHQW2SWLRQV&XUU7UHDW2SWLRQV&DUGLRYDVF0HGS

:HQ3<HWDO8SGDWHGUHVSRQVHDVVHVVPHQWFULWHULDIRUKLJKJUDGHJOLRPDVUHVSRQVH
DVVHVVPHQWLQQHXURRQFRORJ\ZRUNLQJJURXS-&OLQ2QFROS



$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 $33(1',;
 3(5)250$1&(67$786&5,7(5,$
(&2*3HUIRUPDQFH6WDWXV6FDOH

.DUQRIVN\3HUIRUPDQFH6FDOH
*UDGH
'HVFULSWLRQV
3HUFHQW
'HVFULSWLRQ

1RUPDODFWLYLW\)XOO\DFWLYH
DEOHWRFDUU\RQDOOSUHGLVHDVH
SHUIRUPDQFHZLWKRXWUHVWULFWLRQ

1RUPDOQRFRPSODLQWVQR
HYLGHQFHRIGLVHDVH

$EOHWRFDUU\RQQRUPDODFWLYLW\
PLQRUVLJQVRUV\PSWRPVRI
GLVHDVH

6\PSWRPVEXWDPEXODWRU\
5HVWULFWHGLQSK\VLFDOO\VWUHQXRXV
DFWLYLW\EXWDPEXODWRU\DQGDEOH
WRFDUU\RXWZRUNRIDOLJKWRU
VHGHQWDU\QDWXUHHJOLJKW
KRXVHZRUNRIILFHZRUN

1RUPDODFWLYLW\ZLWKHIIRUW
VRPHVLJQVRUV\PSWRPVRI
GLVHDVH

&DUHVIRUVHOIXQDEOHWRFDUU\RQ
QRUPDODFWLYLW\RUWRGRDFWLYH
ZRUN

,QEHGRIWKHWLPH
$PEXODWRU\DQGFDSDEOHRIDOO
VHOIFDUHEXWXQDEOHWRFDUU\RXW
DQ\ZRUNDFWLYLWLHV8SDQG
DERXWPRUHWKDQRIZDNLQJ
KRXUV

5HTXLUHVRFFDVLRQDODVVLVWDQFH
EXWLVDEOHWRFDUHIRUPRVWRI
KLVKHUQHHGV

5HTXLUHVFRQVLGHUDEOHDVVLVWDQFH
DQGIUHTXHQWPHGLFDOFDUH

,QEHG!RIWKHWLPH
&DSDEOHRIRQO\OLPLWHGVHOIFDUH
FRQILQHGWREHGRUFKDLUPRUH
WKDQRIZDNLQJKRXUV

'LVDEOHGUHTXLUHVVSHFLDOFDUH
DQGDVVLVWDQFH

6HYHUHO\GLVDEOHG
KRVSLWDOL]DWLRQLQGLFDWHG'HDWK
QRWLPPLQHQW

EHGULGGHQ&RPSOHWHO\
GLVDEOHG&DQQRWFDUU\RQDQ\
VHOIFDUH7RWDOO\FRQILQHGWREHG
RUFKDLU

9HU\VLFNKRVSLWDOL]DWLRQ
LQGLFDWHG'HDWKQRWLPPLQHQW

0RULEXQGIDWDOSURFHVVHV
SURJUHVVLQJUDSLGO\

'HDG

'HDG


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 3,//$1'%/22'35(6685(',$5<
NCI Neuro-oncology Branch 
9030 Old Georgetown Road, Room 233 
Bethesda, MD 20892 
Telephone:  Fax:  
7LWOH3KDVH,,6WXG\RI6XQLWLQLELQ6DUFRPDVRIWKH&HQWUDO1HUYRXV6\VWHP
3,//DQG%/22'35(6685(',$5<)25681,7,1,%
'D\V±RIHDFKF\FOH&\FOH GD\V 
7RGD\¶VGDWHBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB

&\FOH1XPEHUBBBBBBBBBBBBBBBBBBBBB
3DWLHQW1DPHRULQLWLDOVBBBBBBBBBBBBBBBBBBBBBBB

3DWLHQW6WXG\,'BBBBBBBBBBBBBBBBBBBB



$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH
  
Sunitinib Dose/Frequency: 
 
 
 
Route: 
Oral 
 
  
mg/day 
 
 
Daily 
 
 BLOOD PRESSURE 
 
 BASELINE 
_________ 
 
 WEEKLY 
 
 
  
 
 
DAY # 
DATE- 
TIME 
INITIALS 
Blood Pressure 
DATE 
TIME 
INITIALS 
1 



 




2 



 




3 



 



4 



 



5 



 



6 



 



7 



 



8 



 



9 



 



10 



 



11 



 



12 



 



13 



 



14 



 






$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

DAY # 
DATE 
TIME 
INITIALS 
Blood Pressure 
DATE 
TIME 
INITIALS 
15 
2IIGD\


 



16 
2IIGD\


 



17 
2IIGD\


 



18 
2IIGD\


 



19 
2IIGD\


 



20 
2IIGD\


 



21 
2IIGD\


 




0\VLJQDWXUHVLJQLILHVWKDWWKHVWXG\GUXJVKDYHEHHQWDNHQDVLQGLFDWHG

3DWLHQW¶V6LJQDWXUHBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBBB
'DWHBBBBBBBBBBBBBBBBBBBB


7KLVFDOHQGDULVIRU\RXWRLQGLFDWHWKDW\RXWRRNWKHGUXJVDFFRUGLQJWRWKHLQVWUXFWLRQV 3OHDVH
SXWDFKHFNPDUNRU\RXULQLWLDOVDIWHUHDFKGRVH 3OHDVHVLJQWKLVFDOHQGDUDWWKHHQGRIWKH
F\FOHDQGEULQJWKHFDOHQGDUDQGDOOVWXG\GUXJERWWOHVEDFNWR\RXUQH[W FOLQLFYLVLW

127(6723$7,(17
x %HLQVWUXFWHGWRVWRUH6XQLWLQLEDWURRPWHPSHUDWXUH
x 6XQLWLQLEVKRXOGEHWDNHQRQFHGDLO\ZLWKRUZLWKRXWIRRGDVGHVLUHG
x <RXVKRXOGGULQNSOHQW\RIZDWHURUWDNHUHK\GUDWLRQIOXLGVWRDYRLGGHK\GUDWLRQLI
GLDUUKHDRFFXUV
x 3OHDVHEHDZDUHWKHUHLVDSRVVLELOLW\WKDW6XQLWLQLEFDSVXOHVFDQFDXVHD\HOORZ
GLVFRORUDWLRQRIWKHVNLQRQGLUHFWFRQWDFW,IWKLVKDSSHQV\RXVKRXOGZDVKLPPHGLDWHO\
ZLWKVRDSDQGZDWHU


$EEUHYLDWHG7LWOH 3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH
 0' $1'(56216<03720,19(1725<0'$6,%7


$EEUHYLDWHG7LWOH 3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH


$EEUHYLDWHG7LWOH3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH

 $&7,*5$3+<3$7,(177($&+,1*722/
<RXZLOOEHDVNHGWRSDUWLFLSDWHLQDQRSWLRQDOSRUWLRQRIWKHSURWRFROWRPRQLWRU\RXURYHUDOO
SK\VLFDODFWLYLW\OHYHOVVOHHSGXUDWLRQDQGHIILFLHQF\DPRXQWRIWLPHVSHQWLQVHGHQWDU\
PRGHUDWHYLJRURXVLQWHQVLW\FDWHJRULHV,I\RXFKRRVHWRSDUWLFLSDWH\RXZLOOEHDVNHGWRZHDUD
VPDOOQRQLQYDVLYHZDWFKOLNHGHYLFHFDOOHGDQ$FWL*UDSKVLPLODUWRD)LW%LW
<RXZLOOEHDVNHGWRZHDUWKH$FWL*UDSKKRXUVSHUGD\IRUWKHILUVWF\FOHVRIWKHSURWRFRO
<RXPD\ZHDULWLQWKHVKRZHU<RXVKRXOGUHPRYHLWSULRUWRDQ\05,¶VDVLWFRQWDLQVPHWDO
$WHDFK1,+YLVLWZHZLOOFKDQJHWKHEDWWHULHVIRU\RX2FFDVLRQDOO\\RXPD\EHDVNHGWRPDLO
LWWR1,+WRFKDQJHWKHEDWWHULHVIRU\RX
7KHVHVPDOOPRQLWRUVPD\FDXVHVOLJKWGLVFRPIRUWWRVXEMHFWV1RRWKHUNQRZQULVNVDUH
DVVRFLDWHG



$EEUHYLDWHG7LWOH 3K,,6XQLWLQLE&166DUFRPDV
9HUVLRQ'DWH
 0$1$*(0(172)+<3(57(16,21,1'8&('%<9(*) ,1+,%,7256