Extended Treatment and Follow-up of Subjects Treated With Belumosudil in Study KD025-208 or Study KD025-213
Phase: PHASE2
Conditions: Chronic Graft-versus-host-disease
Sponsor: Kadmon, a Sanofi Company

C o nfi de nti alit y St ate me nt  
T he i nf or mati o n c o ntai ne d her ei n is c o nfi de ntial a n d t he pr o prietar y pr o pert y of Ka d m o n C or p orati o n 
a n d a n y u na ut h orize d use or discl os ure of s uc h i nf or mati o n wit h o ut t he pri or writte n a ut h orizati o n of 
Ka d m o n C or p orati o n is e x pressl y pr o hi bite d.  
C LI NI C A L  S T U D Y P R O T O C O L  
E xte n de d Tre at me nt a n d F oll o w -u p of S u bjects Tre ate d wit h Bel u m os u dil i n  
St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3  
P r ot oc ol N u m ber:  
K D 0 2 5 -2 1 7  
St u d y Dr u g:  
Bel u m os u dil  (f or merl y K D 0 2 5) 
I N D N u m ber: 
I N D 1 2 5 8 9 0 
P h ase : 
2  
S p o ns or:  
Ka d m o n C or p orati o n , L L C 
4 5 0 East 2 9t h Street  
Ne w Y or k, N Y 1 0 0 1 6  
Ori gi n al  P r ot oc ol:  
2 6  J uly  2 0 2 1  
A me n d me nt 1:  
0 1 Se pte m ber  2 0 2 1  
V V- C LI N- 0 6 3 8 9 9 6 1. 0
          N C T: N C T 0 5 3 0 5 9 8 9

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
I N D 1 2 5 8 9 0 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Pr o ce d ures i n C ase of E mer ge nc y  
 
Seri o us A d verse E ve nts  
A n y  s eri o us a d verse e v e nt ( S A E) * occ urri n g i n a s u bject w hile recei vi n g st u d y dr u g or wit hi n 
2 8  da ys  of recei vi n g t heir last d ose of st u d y dr u g, e ve n t h o u g h t he e v e nt ma y n ot a p pear t o be 
st u d y dr u g relate d, m ust be pr o m ptl y re p orte d (wit hi n 2 4 h o urs ) b y tele p h o ne, e-mail,  or telefa x 
t o t he S p o ns or  ( or desi g n ee).   
E mer ge nc y C o nt a ct I nf or m ati o n:  
F or me dic al q uesti o ns c o nt act t he m e dic al m o nit or , 
: 
E mail:
 
P h o ne: 
 
F or S A E re p orti n g, se n d t he S A E f or m, pre g n a nc y f or m or f oll o w -u p wit hi n 2 4  h o urs of 
bec o mi n g a w are t o:  
Ka d m o n P har mac o vi gila nce  
 
or  
Fa x: 
S A E C RI T E RI A  
* A S A E is a n y u nt o war d me dical occ urre nce t hat at a n y d ose res ults i n a n y of t he f oll o wi n g o utc o mes, 
re gar dless of relati o ns hi p t o st u d y dr u g (see Secti o n 7. 3. 1 , Seri o us A d verse E ve nts, f or a d diti o nal 
i nf or mati o n): 
•  
Deat h  
•  
Life -t hreate ni n g a d verse dr u g e ve nt 
•  
I n patie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n 
•  
A persiste nt or si g nifica nt disa bilit y/ i nca pacit y  
•  
A c o n ge nital a n o mal y/ birt h defect  
•  
A n i m p orta nt me dical e ve nt t hat ma y j e o par dize t he s u bj ect a n d ma y re q uire me dical or 
s ur gical i nter ve nti o n t o pre ve nt o ne of t he o utc o mes liste d a b o ve. 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
I N D 1 2 5 8 9 0 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S P O N S O R A P P R O V A L SI G N A T U R E  P A G E   
 
I h a ve rea d a n d a p pr o ve t his pr ot oc ol. M y si g nat ur e, i n c o nj u ncti o n wit h t he si g nat ur e of t he 
I n v esti gat or, c o nfir ms t h e a gree me nt of b ot h parties t hat t he cli nical st u d y will be c o n d ucte d i n 
acc or da nce wit h t he pr ot oc ol a n d all a p plica ble l a ws a n d re g ulati o ns i ncl u di n g, b ut n ot li mite d 
t o, t he I nter nati o nal C o nfere nce o n Har m o nizati o n G ui deli ne f or G o o d Cli nical Practice ( G C P) 
E 6 ( R 2) , a n d t he et hical pri nci ples t hat ha ve t heir ori gi ns i n t he Declarati o n of Helsi n ki. 
 
 
 
 
 
Date of Si g nat ure  
E x ec uti ve Me dical Direct or, Cli nical a n d Re g ulat or y 
De vel o p me nt  
 
( D D M M M Y Y Y Y) 
Ka d m o n C or p orati o n, L L C  
 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
Ka d m o n C or p orati o n  
P a ge 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
I N V E S TI G A T O R SI G N A T UR E P A G E  
I h a ve rea d a n d a p pr o ve t his pr ot oc ol. M y si g nat ur e, i n c o nj u ncti o n wit h t he si g nat ur e of t he 
S p o ns or , c o nfir ms t he a gree me nt of b ot h p arties t hat t he cli nical st u d y will be c o n d ucte d i n 
acc or da nce wit h t he pr ot oc ol a n d all a p plica ble l a ws a n d re g ulati o ns i ncl u di n g, b ut n ot li mite d 
t o, t he I nter nati o nal C o nfere nce o n Har m o nizati o n G ui deli ne f or G o o d Cli nical Practice ( G C P) 
E 6 ( R 2 ), t he C o de of Fe d eral Re g ulati o ns ( C F R), a n d t he et hical pri n ci ples t hat ha ve t heir ori gi ns 
i n t he Declarati o n of Helsi n ki. 
N ot hi n g i n t his d oc u me nt is i nte n de d t o li mit t he a ut h orit y of a p h ysici a n t o pr o vi de e mer ge nc y 
me dical ca re u n der a p pli ca ble re g ulati o ns.  
I n v esti gat or Si g nat ure 
Date of Si g nat ure  
( D D M M M Y Y Y Y) 
Na me of I n v esti gat or ( pl ease pri nt)  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S Y N O P SI S   
St u d y Title  
E xte n de d Treat me nt a n d F oll o w -u p of S u bj ects Treate d wit h Bel u m os u dil i n 
St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3  
Cli nic al P h ase  
2  
St u d y B ac k gr o u n d  
C hr o nic graft -vers us -h ost dise ase (c G V H D) re mai ns a maj or c o m plicati o n of 
all o ge neic he mat o p oietic cell tra ns pla ntati o n ( H C T) occ urri n g i n a p pr o xi matel y 
5 0 % of tra ns pla nt reci pie nts a n d i n v ol vi n g m ulti ple or ga ns. P atie nts wit h 
c G V H D re q uire pr ol o n ge d i m m u n os u p pressi ve treat me nt f or a n a vera ge of 2 t o 
3 years fr o m t he i nitial dia g n osis, wit h 1 0 % of t h ose s ur v i vi n g f or at least 
7  years still re q uiri n g i m m u n os u p pressi ve treat me nt at t hat ti me a n d be y o n d.  
T here re mai ns s u bsta ntial u n met me dical nee d f or t hera pies wit h i m pr o ve d 
t olera bilit y a n d effecti ve ness f or a d ults a n d a d olesce nts wit h c G V H D.  
B el u m os u dil ( pre vi o usl y  k n o w n as K D 0 2 5) is a n orall y a vaila ble R h o -ass ociate d 
c oile d -c oil ki nase 2 ( R O C K 2) selecti ve i n hi bit or t hat has bee n s h o w n t o be 
acti ve a n d well -t olerate d i n c G V H D.  St u d y K D 0 2 5-2 0 8 e nr olle d s u bj ects wit h 
acti ve c G V H D w h o ha d pre vi o usl y recei ve d n o  m ore t ha n 3 pri or li nes of 
treat me nt.  St u d y K D 0 2 5-2 1 3 e nr olle d s u bj ects w h o ha d pre vi o usl y recei ve d 2  t o 
5  pri or li nes of treat me nt.  O ver t w o -t hir ds of c G V H D patie nts treate d wit h 
bel u m os u dil i n t hese 2  trials a c hie ve d cli nical res p o nses.  
I n b ot h St u d y K D 0 2 5 -2 0 8 a n d St u d y K D 0 2 5 -2 1 3, s u bj ects were treate d wit h 
bel u m os u dil u ntil c G V H D pr o gressi o n or u nacce pta ble t o xicit y.  Se veral 
s u bj ects re mai n o n acti ve treat me nt.   
T his st u d y will pr o vi de e xte n de d  treat me nt a n d f oll o w-u p f or t hese s u bj ects 
utilizi n g t he sa me d ose a n d treat me nt sc he d ule of bel u m os u dil t hat eac h s u bj ect 
was recei vi n g i n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3.  
St u d y O bjecti ve  
T he o bj ecti ve of t his st u d y is t o e val uate l o n g -ter m safet y a n d efficac y of 
bel u m os u dil i n s u bj ects wit h c G V H D w h o ha ve pre vi o usl y bee n treate d wit h 
bel u m os u dil .  
St u d y  Desi g n  
T his will b e a P hase 2, o pe n -la bel, l o n g-ter m treat me nt a n d f oll o w-u p st u d y i n 
s u bj ects wit h c G V H D w h o ha ve bee n pre vi o usl y treate d wit h bel u m os u dil i n 
St u d y K D 0 2 5 -2 0 8 or i n St u d y K D 0 2 5 -2 1 3.  
S u bj ects will n ot be scree ne d.  
S u bj ects w h o ha ve si g ne d t he  i nf or me d c o nse nt f or m will be e nr olle d i n 
St u d y  K D 0 2 5 -2 1 7 if t he y ha ve met 1 of t he f oll o wi n g c o n diti o ns:  
•  
Acti vel y recei vi n g bel u m os u dil or i n l o n g -ter m f oll o w-u p ( L T F U) i n 
St u d y  K D 0 2 5 -2 0 8  or St u d y K D 0 2 5 -2 1 3  
•  
E nr olle d i n t he C o m pa ni o n St u d y as s pecifie d i n St u d y K D 0 2 5 -2 1 3 
A me n d me nt 2 a n d recei ve d at least 6 m o nt hs of treat me nt or is i n L T F U  
After si g ni n g t he I C F, at Baseli ne , s u bj ects will u n der g o effi cac y assess me nts b y 
Cli nicia n -re p orte d  Gl o bal c G V H D Acti vit y Assess me nt, res p o nse assess me nt, 
p ul m o nar y f u ncti o n tests, Lee S y m pt o m Scale ( L S S) sc ore, a n d d oc u me ntati o n 
of c ortic oster oi d d osa ge a n d/ or ot her t hera pies f or c G V H D.  S u bj ects will 
u n der g o safet y assess me nts i ncl u di n g s y m pt o m -directe d  p h ysica l e xa mi nati o n 
( P E), vital si g ns, wei g ht, hei g ht, Kar n ofs k y P erf or ma nce St at us  ( K P S) sc ore, 
he mat ol o g y a n d cli nical c he mistr y la b orat or y testi n g, pre g na nc y testi n g, 1 2 -lea d 
electr ocar di o gra m ( E C G ), d oc u me nti n g c o nc o mita nt me dicati o ns, a n d 
m o nit ori n g f or a d verse e ve nts ( A Es ).  S u bj ects will c o nti n ue o n t heir sa me 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
d osi n g re gi me n as t he y recei ve d i n St u d y K D 0 2 5 -2 0 8 or St u d y  K D 0 2 5 -2 1 3: 
bel u m os u dil 2 0 0 m g o nce dail y ( Q D ), 2 0 0 m g t wice dail y (BI D ), or 4 0 0 m g Q D.  
If t he I n vesti gat or re d uce d t he d ose, i.e., a s ubject recei ve d a re d uce d d ose of 
bel u m os u dil i n eit her St u d y  K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3, t he s u bj ect w o ul d 
c o nti n ue t o recei ve t hat sa me re d uce d d ose treat me nt wit h bel u m os u dil 
t hr o u g h o ut St u d y K D 0 2 5-2 1 7  or u ntil t he A E  t hat le d t o t he t e m p orar y d ose 
re ducti o n ha d  res ol ve d, i n w hi c h t he d ose treat me nt ca n res u me at t he ori gi nal 
d ose at t he discreti o n of t he I n vesti gat or.   S u bj ects will be gi ve n a st u d y dr u g 
diar y t o rec or d dail y d osi n g.  S u bj ects ma y be a d mi nistere d t he first d ose eit her 
i n t he cli nic or self-a d mi nistere d at h o me.  
At 3 m o nt hs after Baseli ne  a n d e ver y 3 m o nt hs t hereafter ( ± 1 4 da ys), s u bj ects 
will re p ort t o t he cli nic f or t he sa me efficac y a n d safet y assess me nts a n d 
dis pe nsi n g of bel u m os u dil  as Baseli ne .  T he st u d y dr u g diaries f or t he past 
3  m o nt hs will be c ollecte d, a n d ne w st u d y dr u g diaries dis pe nse d.  A n y 
re mai ni n g bel u m os u dil will be c ollecte d. 
S u bj ects ma y recei ve bel u m os u dil  i n St u d y  K D 0 2 5 -2 1 7 f or u p t o a n a d diti o nal 
2  years , at t he discreti o n of t he In vesti gat or (a n d wit h g ui da nce fr o m t he me dical 
m o nit or) , be y o n d w hat t he y ha d recei ve d i n St u d y K D 0 2 5-2 0 8 or St u d y  K D 0 2 5 -
2 1 3 .  S u bj ects will be treate d wit h bel u m os u dil u ntil c G V H D pr o gressi o n or 
u nacce pta ble t o xicit y.  
S u bj ects will ret ur n t o t he cli nic f or a 2 8 -da y F oll o w -u p Visit  2 8 ( ± 7 da ys) at 
2 8  da ys after t he last d ose of st u d y dr u g.  After t he 2 8 -da y  F oll o w -U p  Visit has 
bee n c o m plete d, s u bj ects will ha ve L T F U  a p pr o xi matel y e ver y 3  m o nt hs u ntil a 
fail ure-free s ur vi val ( F F S) e ve nt occ urs.   T his L T F U assess me nt wi ll occ ur b y 
s u bj ects bei n g  c o ntacte d b y tel e p h o ne, e -mail, or p ostal mail t o c o nfir m s ur vi val 
stat us, a n y i nitiati o n of ne w s yste mic c G V H D t hera pies, a n d rela pse of 
u n derl yi n g disease.  Alter nati vel y, t his i nf or mati o n ma y be o btai ne d fr o m t he 
s u bj ect’s me dical rec or ds. 
N u m ber of St u d y Ce nters  
A p pr o xi matel y 2 0  
N u m ber of S u bjects  
A p pr o xi matel y 7 0  
A p pr o xi m ate D ur ati o n of 
S u bject P artici p ati o n  
S u bj ects ma y recei ve bel u m os u dil  u p t o a n a d diti o nal 2 years  be y o n d w hat t he y 
ha d recei ve d i n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3 , at t he discreti o n of t he 
In vesti gat or a n d wit h g ui da nc e fr o m t he me dical m o nit or.  
S u bj ects will be treate d wit h bel u m os u dil u ntil c G V H D pr o gressi o n or 
u nacce pta ble t o xicit y.  
S u bj ects will ret ur n t o t he cli nic f or a 2 8 -da y F oll o w -u p Visit at 2 8 da ys 
( ± 7  da ys) after  t he last d ose of st u d y dr u g.  S u bj ects will ha ve L T F U  
a p pr o xi matel y e ver y 3 m o nt hs u ntil a F F S e ve nt occ urs .  Aft er t he 2 8-da y 
F oll o w -u p Visit has bee n c o m plete d, s u bj ects will be c o ntacte d a p pr o xi matel y 
e ver y 3 m o nt hs b y tele p h o ne, e -mail, or p ostal mail t o c o nfir m s ur vi val stat us, 
a n y i nitiati o n of ne w s yste mic c G V H D t hera pies, a n d rela pse of u n derl yi n g 
disease.   
St u d y Tre at me nt  
B el u m os u dil will be a d mi nistere d orall y at t he sa me d ose t he s u bj ect recei ve d i n 
St u d y K D 0 2 5 -2 0 8 or i n St u d y K D 0 2 5 -2 1 3.  
S u bj ects will be pr o vi de d wit h a n a de q uate s u p pl y of bel u m os u dil.  St u d y dr u g 
acc o u nti n g will be perf or me d at eac h visit.  
Criteri a f or I ncl usi o n a n d 
E xcl usi o n  
I ncl usi o n Criteri a: 
1.  S u bj ects m ust ha ve bee n treat e d wit h bel u m os u dil f or at least 1 of t he 
f oll o wi n g: 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
a. 
Acti vel y r ecei v i n g bel u m os u dil o n St u d y  K D 0 2 5 -2 0 8  or 
St u d y  K D 0 2 5 -2 1 3  (e xcl u di n g a d ults i n t he C o m pa ni o n St u d y 
a n d e xcl u di n g a d olesce nts e nr olle d u n der K D 0 2 5 -2 1 3 
A me n d me nt 2 [0 1  J u ne 2 0 2 0]). 
b.  Is i n L o n g -ter m F oll o w -u p ( L F T U) o n St u d y K D 0 2 5 -2 0 8  or 
St u d y  K D 0 2 5 -2 1 3 .  L o n g-ter m F oll o w -u p  will be defi ne d as 
t he peri o d after e n di n g treat me nt wit h bel u m os u dil a n d u ntil a 
F F S e ve nt occ urs.  
c. 
A d ult e nr olle d i n t he C o m pa ni o n St u d y u n der K D 0 2 5 -2 1 3 
A me n d me nt 2 ( 0 1  J u ne 2 0 2 0) a n d has recei ve d at least 
6  m o nt hs of treat me nt of bel u m os u dil or is i n L T F U  
2.  Fe male s u bj ects of c hil d beari n g p ote ntial ha ve a ne gati ve pre g na nc y test 
at e nr oll me nt. Fe males of c hil d beari n g p ote ntial are defi ne d as se x uall y 
mat ure fe males wit h o ut pri or h ysterect o m y or w h o ha ve ha d a n y  
e vi de nce of me nses i n t he past 1 2 m o nt hs. H o we ver, fe males w h o ha ve 
bee n a me n orr heic f or 1 2 or m ore m o nt hs are still c o nsi dere d t o be of 
c hil d beari n g p ote ntial if t he a me n orr hea is p ossi bl y d ue t o pri or 
c he m ot hera p y, a nti -estr o ge ns, or o varia n s u p pressi o n . 
3.  Se x uall y acti ve fe males of c hil d beari n g p ote ntial e nr olle d i n t he st u d y 
m ust a gree t o use 2  f or ms of a cce pte d met h o ds of c o ntrace pti o n d uri n g 
t he c o urse of t he st u d y a n d f or 3 m o nt hs after t heir last d ose of st u d y 
dr u g. Effecti ve birt h c o ntr ol i ncl u des:  
a. 
I ntra uteri ne de vice pl us 1 barrier met h o d 
b.  Sta ble d oses of h or m o nal c o ntrace pti o n f or at least 3 m o nt hs 
(e. g., oral, i nj ecta ble, i m pla nt, tra ns der mal) pl us 1  barrier 
met h o d  
c. 
2  barrier met h o ds.  Effecti ve barrier met h o ds are male or 
fe male c o n d o ms, dia p hra g ms, a n d s per mici des (crea ms or gels 
t hat c o ntai n a c he mical t o kill s per m) or 
d.  A vasect o mize d part ner  
4.  F or male s u bj ects w h o are se x uall y acti ve a n d w h o are part ners of 
fe males of c hil d beari n g p ote ntial: a gree me nt t o use 2  f or ms of 
c o ntrace pti o n a n d t o n ot d o n at e s per m d uri n g t he treat me nt p eri o d a n d 
f or at least 3 m o nt hs after t he l ast d ose of st u d y dr u g. 
5.  S u bj ect ( or t he s u bj ect’s le gall y a ut h orize d re prese ntati ve) is a ble t o 
pr o vi de writte n i nf or me d c o ns e nt pri or t o t he perf or ma nce of a n y st u d y -
s pecific pr oced ures.  
6.  It is i n t he best i nterest of t he s u bj ect t o partici pate i n t he st u d y. 
 
E xcl usi o n Criteri a  
1.  Fe male s u bj ect w h o is pre g na nt or breastfee di n g  
2.  S u bj ect c o nsi dere d u nli kel y t o a d here t o treat me nt a n d/ or f oll o w 
pr ot oc ol i n t he o pi ni o n of t he I n vesti gat or  
Effic ac y F oll o w -u p 
V ari a bles  
 
•  
D urati o n of Res p o nse s (D O R ):  Res p o nse  is defi ne d b y t he 2 0 1 4 
Nati o nal I nstit utes of Healt h ( NI H) C o nse ns us De vel o p me nt Pr oj ect o n 
cli nical trials i n c G V H D a n d are assesse d b y i n vesti gat ors  
•  
C ha n ge i n Lee S y m pt o m Scal e Sc ore ( L S S)  
•  
Ti me t o Ne xt Treat me nt  ( T T N T) 
•  
F F S  
•  
O verall S ur vi val ( O S)  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  
P erce nta ge of s u bj ects w h o ha ve a best res p o nse of P R a n d perce nta ge 
of s u bj ects w h o ha ve a best res p o nse of C R  
•  
Res p o nse b y i n di vi d ual or ga n  
•  
C ha n ge i n cortic oster oi d d ose  
•  
C ha n ge i n c G V H D Gl o bal Se verit y Rati n g base d o n t he 
Cli nicia n -re p orte d Gl o bal c G V H D Acti vit y Assess me nt  
S afet y F oll o w -u p V ari a bles  
Safet y assess me nts will be perf or me d at re g ular i nter vals a n d will i ncl u de A Es, 
Gra d e ≥ 3 A Es, seri o us a d vers e e ve nts (S A Es ), P Es, vital si g n meas ure me nts, 
cli nical la b orat or y e val uati o ns, a n d E C Gs.  Reas o ns f or treat me nt 
disc o nti n uati o n will be d oc u me nte d.   
T he A E re p orti n g peri o d f or a s u bj ect e nr olle d i n t he st u d y will be gi n w he n t he 
s u bj ect si g ns t he i nf or me d c o nse nt a n d is c o nti n ue d t hr o u g h t he 2 8-da y F oll o w -
u p Visit at 2 8 da ys  ( ± 7 da ys) after t heir last d ose st u d y  dr u g.  
St atistic al A n al ysis  
A n i nteri m a nal ysis will be perf or me d w he n all patie nts ha ve c o m plete d at least 
3  years of treat me nt wit h bel u m os u dil or wit h dre w earlier ( n ot i ncl usi ve of t he 
c o m pa ni o n st u d y s u bj ects).   
 
St u d y S u bjects  
De m o gra p hic (e. g., ge n der, a ge, a n d race) a n d Baseli ne  c har acteristics will be 
s u m marize d.   
 
Effic ac y A n al yses:  
T he efficac y e n d p oi nt a nal yses i ncl u de  
•  
D O R  
•  
C ha n ge i n L S S  
•  
T T N T  
•  
F F S  
•  
O S  
•  
P r o p orti o n of s u bj ects wit h a C R a n d pr o p orti o n wit h a P R 
•  
Res p o nse b y i n di vi d ual or ga n  
•  
C ha n ge i n c ortic oster oi d use  
•  
C ha n ge i n c G V H D gl o bal se verit y rati n g base d o n t he 
Cli nicia n -re p orte d Gl o bal c G V H D Acti vit y Assess me nt.  
 
S afet y A n al yses:  
Safet y a nal yses will be perf or me d o n all s u bj ects w h o recei ve at least 1  d ose of 
bel u m os u dil . 
A d verse e ve nts  will be c o de d usi n g t he Me dical Dicti o nar y of Re g ulat or y 
Acti vities ( Me d D R A v ersi o n 2 4 . 0 or greater).  T he n u m ber a n d perce nta ges of 
s u bj ects e x perie nci n g treat me nt-e mer ge nt A Es will be ta b ul ate d b y S yste m  
O r ga n C lass a n d P referre d T er m ( P T).  T he n u m ber of e ve nts b y P T  will als o be 
s u m marize d.  T a b ulati o n b y ma xi m u m se verit y a n d relati o ns h i p t o treat me nt will 
als o be i ncl u de d b y treat me nt gr o u p.  S u m mar y s u bj ect listi n g will be pr o vi de d 
f or S A Es, A Es res ulti n g i n st u d y disc o nti n uati o n, a n d deat hs. 
T he A Es, S A Es, relate d A Es, relate d S A Es, Gra de ≥ 3 A Es, relate d Gra de ≥ 3 
A Es, deat hs, a n d A E s lea di n g t o wit h dra wal a n d treat me nt disc o nti n uati o n will 
be s u m marize d.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
Ka d m o n C or p orati o n  
P a ge 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
La b orat or y res ults  a n d i nci de nce of la b orat or y a b n or malities  will be s u m marize d 
b y treat me nt gr o u p.   T he w orst o n -st u d y gra de d uri n g t he treat me nt peri o d will 
be s u m marize d. T he i nci de nce of G ra de ≥ 3 la b orat or y a b n or malities u n der 
treat me nt a n d s hifts i n t o xicit y gra di n g fr o m Baseli ne  t o hi g hest gra de 
p ost -baseli ne will be dis pla ye d.  
Vital si g n meas ure me nts a n d E C Gs will be s u m marize d b y treat me nt gr o u p at 
eac h sc he d ule d ti me p oi nt usi n g descri pti ve statistics a n d i ncl u de d i n data 
listi n gs.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
T A B L E  O F C O N T E N T S  
C LI NI C A L S T U D Y P R O T O C O L  ............................................................................................................... 1  
S P O N S O R A P P R O V A L SI G N A T U R E P A G E  ........................................................................................... 3  
I N V E S TI G A T O R SI G N A T U R E P A G E ...................................................................................................... 4  
S Y N O P SI S  .................................................................................................................................................... 5  
T A B L E O F C O N T E N T S  ............................................................................................................................ 1 0  
LI S T O F T A B L E S  ...................................................................................................................................... 1 3  
LI S T O F FI G U R E S  .................................................................................................................................... 1 4  
LI S T O F A B B R E VI A TI O N S  ..................................................................................................................... 1 5  
1  
I N T R O D U C TI O N ................................................................................................................................ 1 7  
1. 1  
C hr o nic Graft -vers us -H ost Disease  ............................................................................................ 1 7  
1. 2  
R h o -Ass ociate d Pr otei n Ki nases ................................................................................................. 1 7  
1. 3  
N o n -cli nical Bac k gr o u n d of Bel u m os u dil  .................................................................................. 1 8  
1. 4  
Cli nical Bac k gr o u n d of Bel u m os u dil  ......................................................................................... 1 9  
1. 4. 1  St u d y K D 0 2 5 -2 0 8  ....................................................................................................................... 1 9  
1. 4. 2  St u d y K D 0 2 5 -2 1 3  ....................................................................................................................... 2 4  
1. 5  
St u d y Rati o nale  ........................................................................................................................... 2 9  
1. 6  
S u m mar y of  K n o w n a n d P ote ntial Ris ks a n d Be nefits t o H u ma n S u bj ects  ............................... 3 0  
2  
S T U D Y O BJ E C TI V E S  ........................................................................................................................ 3 1  
3  
I N V E S TI G A TI O N A L P L A N .............................................................................................................. 3 2  
3. 1  
St u d y Desi g n ............................................................................................................................... 3 2  
3. 2  
Esti mate d St u d y D urati o n  ........................................................................................................... 3 3  
4  
S T U D Y P O P U L A TI O N  ....................................................................................................................... 3 4  
4. 1  
N u m ber of S u bjects  .................................................................................................................... 3 4  
4. 2  
St u d y Ce nters  .............................................................................................................................. 3 4  
4. 3  
I ncl usi o n Criteria ........................................................................................................................ 3 4  
4. 4  
E xcl usi o n Criteria  ....................................................................................................................... 3 5  
4. 5  
Scree ni n g  .................................................................................................................................... 3 5  
4. 6  
Wit h dra wal Criteria  .................................................................................................................... 3 5  
4. 7  
Re place me nts  .............................................................................................................................. 3 6  
4. 8  
Treat me nt Di sc o nti n uati o n ......................................................................................................... 3 6  
5  
S T U D Y T R E A T M E N T  ....................................................................................................................... 3 7  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5. 1  
I n vesti gati o nal Pr o d uct ............................................................................................................... 3 7  
5. 2  
D osa ge a n d A d mi nistrati o n  ........................................................................................................ 3 7  
5. 3  
Treat me nt Assi g n me nt  ................................................................................................................ 3 7  
5. 4  
Bli n di n g  ...................................................................................................................................... 3 8  
5. 5  
Treat me nt C o m pli a nce ............................................................................................................... 3 8  
5. 6  
Misse d D oses  .............................................................................................................................. 3 8  
5. 7  
Pr o d uct Acc o u nta bilit y  ............................................................................................................... 3 9  
5. 8  
C o nc o mita nt Me dicati o ns a n d Pr oce d ures  ................................................................................. 3 9  
5. 8. 1  C ortic oster oi ds  ............................................................................................................................ 3 9  
5. 8. 2  S yste mic c G V H D T hera pies ....................................................................................................... 3 9  
5. 8. 3  T o pical / Or ga n S pecific T hera pies f or c G V H D  ........................................................................ 3 9  
5. 8. 4  C Y P 3 A 4 I n d ucers  ...................................................................................................................... 3 9  
5. 8. 5  Dr u gs Pr ol o n gi n g t he Q Tc I nter val  ............................................................................................ 4 0  
5. 8. 6  Pr o hi bite d C o nc o mita nt Me dicati o ns  ......................................................................................... 4 0  
5. 9  
Treat me nt of O ver d ose  ............................................................................................................... 4 0  
5. 1 0  
D ose M o dificati o n G ui deli nes  .................................................................................................... 4 0  
6  
S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S  ............................................................................... 4 2  
6. 1  
Sc he d ule of Assess me nts  ............................................................................................................ 4 2  
6. 2  
St u d y Visits ................................................................................................................................. 4 2  
6. 2. 1  Scree ni n g  .................................................................................................................................... 4 2  
6. 2. 2  Baseli ne Visit  .............................................................................................................................. 4 2  
6. 2. 3  M o nt h 3 Visit a n d E ver y 3 M o nt h Visits T hereafter ( ± 1 4 da ys)  ............................................... 4 3  
6. 2. 4  2 8 Da y F oll o w -U p Visit  ............................................................................................................. 4 4  
6. 2. 5  L o n g -ter m F oll o w-u p  ................................................................................................................. 4 5  
6. 2. 6  U nsc he d ule d Visit  ....................................................................................................................... 4 5  
6. 3  
Effica c y E n d p oi nts ..................................................................................................................... 4 5  
6. 4  
Safet y E n d p oi nts  ......................................................................................................................... 4 6  
7  
S A F E T Y  ............................................................................................................................................... 4 8  
7. 1  
Safet y Para meters  ....................................................................................................................... 4 8  
7. 2  
A d verse E ve nt Defi niti o n  ........................................................................................................... 4 8  
7. 3  
E val uati n g A d verse E ve nts  ......................................................................................................... 4 8  
7. 3. 1  Seri o us A d verse E ve nts  .............................................................................................................. 4 9  
7. 3. 2  Pr ot oc ol -Relate d A d verse E ve nts  ............................................................................................... 5 0  
7. 3. 3  Relati o ns hi p t o St u d y Dr u g  ........................................................................................................ 5 0  
7. 3. 4  Rec or di n g A d verse E ve nts  ......................................................................................................... 5 0  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
7. 3. 5  Seri o us A d verse E ve nt Re p orti n g  ............................................................................................... 5 0  
7. 3. 5. 1  
Ti mefra me f or Re p orti n g  ..................................................................................................... 5 0  
7. 3. 5. 2  
S A E I nf or mati o n t o be Pr o vi de d b y t he I n vesti gat or  ........................................................... 5 1  
7. 3. 5. 3  
Pre g na nc y  ............................................................................................................................. 5 2  
7. 3. 5. 4  
Re g ulat or y Re p orti n g  ........................................................................................................... 5 3  
7. 4  
Ot her Safet y C o nsi derati o ns  ....................................................................................................... 5 3  
7. 4. 1  La b orat or y Data  .......................................................................................................................... 5 3  
7. 4. 2  F oll o w -U p of A d verse E ve nts  .................................................................................................... 5 4  
8  
S T U D Y S T O P PI N G R U L E S  ............................................................................................................... 5 5  
9  
S T A TI S TI C A L C O N SI D E R A TI O N S  ................................................................................................. 5 6  
9. 1  
H y p ot hesis  .................................................................................................................................. 5 6  
9. 2  
Sa m ple Size a n d P o wer Calc ulati o n  ........................................................................................... 5 6  
9. 3  
A nal ysis P o p ulati o ns  .................................................................................................................. 5 6  
9. 4  
S u b gr o u p A nal yses  ..................................................................................................................... 5 6  
9. 5  
Data A nal ysis  .............................................................................................................................. 5 6  
9. 6  
I nteri m A nal ysis ......................................................................................................................... 5 6  
9. 7  
Efficac y A nal yses  ....................................................................................................................... 5 6  
9. 8  
E x pl orat or y A nal yses  ................................................................................................................. 5 6  
9. 9  
Safet y A nal yses  .......................................................................................................................... 5 7  
9. 1 0  
P har mac o ki netic A nal yses  .......................................................................................................... 5 7  
9. 1 1  
P har mac o d y na mic A nal yses  ....................................................................................................... 5 7  
1 0  D A T A Q U A LI T Y A S S U R A N C E  ....................................................................................................... 5 8  
1 1  R E G U L A T O R Y O B LI G A TI O N S & C O M P LI A N C E S T A T E M E N T  ............................................... 5 9  
1 2  E T HI C A L A S P E C T S  ........................................................................................................................... 6 0  
1 2. 1  
L ocal Re g ulati o ns  ....................................................................................................................... 6 0  
1 2. 2  
I nf or me d C o nse nt ....................................................................................................................... 6 0  
1 2. 3  
Researc h Et hics C o m mittees  ...................................................................................................... 6 1  
1 2. 4  
F ut ure Use of S u bject Sa m ples  ................................................................................................... 6 1  
1 3  C O N DI TI O N S F O R M O DI F YI N G T H E P R O T O C O L  ...................................................................... 6 2  
1 4  C O N DI TI O N S F O R T E R MI N A TI N G T H E S T U D Y  ......................................................................... 6 3  
1 5  S T U D Y D O C U M E N T A TI O N, C R F S, A N D R E C O R D K E E PI N G  ................................................... 6 4  
1 5. 1  
I n vesti gat or’s Files a n d Rete nti o n of D oc u me nts ....................................................................... 6 4  
1 5. 2  
S o urce D oc u me nts a n d Bac k gr o u n d Data  .................................................................................. 6 4  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 5. 3  
A u dits a n d I ns pecti o ns  ................................................................................................................ 6 5  
1 5. 4  
Electr o nic Case Re p ort F or ms  .................................................................................................... 6 5  
1 6  M O NI T O RI N G O F T H E S T U D Y  ....................................................................................................... 6 6  
1 7  C O N FI D E N TI A LI T Y O F T RI A L D O C U M E N T S A N D S U BJ E C T R E C O R D S  ............................... 6 7  
1 8  P U B LI C A TI O N O F D A T A A N D P R O T E C TI O N O F T R A D E S E C R E T S  ....................................... 6 8  
1 9  R E F E R E N C E S  ..................................................................................................................................... 6 9  
A p pe n di x  A: Sc he d ule of Assess me nts  ...................................................................................................... 7 2  
A p pe n di x  B: Cli nicia n -re p orte d Gl o bal c G V H D Acti vit y Assess me nt ...................................................... 7 4  
A p pe n di x  C: c G V H D Res p o nse Assess me nt  .............................................................................................. 7 8  
A p pe n di x  D: Lee c G V H D S y m pt o m Sc ore  ................................................................................................ 7 9  
A p pe n di x  E: Kar n ofs k y Perf or ma nce Scale  ............................................................................................... 8 0  
A p pe n di x  F: E q uati o ns t o Pre dict Gl o mer ular Filtrati o n Rate ( M D R D -4)  ................................................. 8 1  
A p pe n di x  G: Deter mi ni n g Relati o ns hi p of A Es t o St u d y Dr u g  .................................................................. 8 2  
A p pe n di x  H: Dr u gs t hat I n d uce C Y P 3 A 4  ................................................................................................... 8 4  
A p pe n di x  I: Dr u gs T hat I n d uce a n d I n hi bit C Y P 1 A 2 ................................................................................ 8 5  
A p pe n di x  J: Dr u gs T hat Pr ol o n g Q T c ........................................................................................................ 8 6  
A p pe n di x  K: Pre d nis o ne D ose E q ui vale nts  ................................................................................................ 8 7  
 
L I S T O F T A B L E S  
T a ble 1.  
Pri mar y Efficac y E n d p oi nt Res ults fr o m St u d y K D 0 2 5 -2 0 8  ............................................ 2 2  
T a ble 2.  
Safet y Res ults fr o m St u d y K D 0 2 5 -2 0 8  ............................................................................ 2 3  
T a ble 3.  
Pri mar y Efficac y E n d p oi nt Res ults fr o m St u d y K D 0 2 5 -2 1 3  ............................................ 2 7  
T a ble 4.  
Safet y Res ults fr o m St u d y K D 0 2 5 -2 1 3  ............................................................................ 2 8  
T a ble 5.  
G ui deli nes f or t he Ma na ge me nt of T E A Es wit h Bel u m os u dil Treat me nt  ........................ 4 0  
T a ble 6.  
Bel u m os u dil D ose Decre me nts  ......................................................................................... 4 1  
T a ble 7.  
Sc he d ule of Assess me nts  .................................................................................................. 7 2  
T a ble 8.  
E xa m ples of Cli nical I n d ucers o f C Y P 3 A 4 ...................................................................... 8 4  
T a ble 9.  
E xa m ples of Cli nical I n d ucers/I n hi bit ors of C Y P 1 A 2  ..................................................... 8 5  
T a ble 1 0.  
E xa m ples of Dr u gs t hat Pr ol o n g Q T c  ............................................................................... 8 6  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
L I S T O F FI G U R E S  
N o t a ble of fi g ures e ntries f o u n d.  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
LI S T O F A B B R E VI A TI O N S   
A E  
A d verse e ve nts  
B A/ B E  
Bi oa vaila bilit y/ Bi oe q ui v ale nce  
BI D  
T wice dail y  
CI  
C o nfi de nce i nter val  
C ma x  
Ma xi m u m c o nce ntrati o n o n c o nce ntr ati o n -ti me c ur ve 
C NI  
Calci ne uri n i n hi bit or  
C R  
C o m plete res p o nse  
C S R  
Cli nical St u d y Re p ort  
C T C A E  
C o m m o n Ter mi n ol o g y Criteria f or A d verse E v e nts  
c G V H D  
C hr o nic graft -v ers us -h ost disease  
D O R  
D urati o n of res p o ns e  
E C G  
Electr ocar di o gra m  
E C P  
E xtrac or p oreal p h ot o p heresis  
e C R F 
Electr o nic case re p ort f or m  
E O S  
E n d -of -St u d y  
E O T  
E n d -of -Treat me nt  
F D A  
F o o d a n d Dr u g A d mi nistrati o n  
F F S  
Fail ure -free s ur vi val 
G C P  
G o o d Cli nical Practice  
GI  
Gastr oi ntesti nal  
H C T  
He mat o p oietic cell tr a ns pla ntati o n  
I B 
I n v esti gat or’s Br oc h ure 
I C F 
I nf or me d C o nse nt F or m 
I E C 
I n d e pe n de nt Et hics C o m mittee 
I L 
I nterle u ki n 
I N D 
I n v esti gati o nal Ne w Dr u g 
I R B 
I nstit uti o nal Re vie w B oar d 
K P S  
Kar n ofs k y Perf or ma n ce Scale  
L R  
Lac k of res p o nse  
L S S  
Lee c G V H D S y m pt o m Scale  
L T F U  
L o n g -t er m F oll o w-u p  
Me d D R A  
Me dical Dicti o nar y of Re g ul at or y Acti vities  
M H C  
Maj or H ist oc o m pati bilit y C o m ple x  
mI T T  
M o difie d I nte nt -t o-Treat P o p ulati o n  
NI H  
Nati o nal I nstit ute s of Healt h  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
O S  
O verall s ur vi val  
P E  
P h ysical e x a mi nati o n  
P K  
P har mac o ki netic  
P R  
Partial res p o nse  
P T  
Preferre d Ter m  
Pt R  
P oi nt re d ucti o n  
Q D  
O nce dail y  
R O C K  
R h o -ass ociate d c oile d -c oil ki nases  
S A E  
Seri o us a d verse e ve nt  
T E A E  
Treat me nt -e mer ge nt a d verse e v e nt  
T F H  
T f ollic ular hel per  
T H 1 7  
T hel per cell 1 7  
T T N T  
Ti me t o ne xt treat me nt  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1  I N T R O D U C TI O N  
1. 1  C hr o nic Gr aft -v ers us -H ost Dise ase   
C hr o nic graft vers us h ost disease (c G V H D) re m ai ns a maj or c o m plicati o n of all o ge neic 
he mat o p oietic cell tra ns pla ntati o n ( H C T) i n v ol vi n g m ulti ple or ga ns a n d occ urri n g i n u p t o 
7 0 %  of tra ns pla nt r eci pie nt s de pe n di n g u p o n d o n or a n d tra ns pla nt c haracteristic s.1  M ultice nter 
a n d re gistr y data s h o w a c u m ulati ve i nci de nce of 3 0 % t o 5 0 %. 2 ,3  Patie nts wit h c G V H D re q uire 
pr ol o n ge d i m m u n os u p pressi ve treat me nt f or a n a vera ge of 2 t o 3 years fr o m t he i nitial dia g n osis, 
wit h 1 0 % of t h ose s ur vi vi n g  f or at least 7 years still re q uiri n g i m m u n os u p pressi ve treat me nt at 
t hat ti me a n d be y o n d.4  
Gl uc oc ortic oi ds, wit h or wit h o ut calci ne uri n i n hi bit or s ( C NIs), re mai n t he sta n dar d i nitial 
treat me nt, b ut are ass ociate d wit h si g nifica nt si de effects a n d u nsatisfact or y o utc o mes, 
partic ularl y f or patie nts wit h hi g h -ris k feat ures of c G V H D.5 
Base d u p o n d ata fr o m St u d y K D 0 2 5 -2 1 3, t he F o o d a n d Dr u g A d mi nistrati o n ( F D A) a p pr o ve d 
R E Z U R O C K ( b el u m os u dil)  f or t he treat me nt of a d ult a n d pe diatric patie nts 1 2 years a n d ol d er 
wit h c G V H D  after fail ure of at least 2  pri or li nes of s yste mic t hera p y  (Secti o n  1. 4. 2 ).6  T his is t he 
sec o n d F D A a p pr o ve d dr u g i n dicat e d s pecifi call y f or patie nts wit h c G V H D. 
T he first F D A a p pr o ve d c G V H D t hera p y is I br uti ni b (I M B R U VI C A) f or t he treat me nt of a d ult 
patie nts wit h c G V H D aft er fail ure of o ne or m ore li nes of s yste mic t hera p y base d u p o n data fr o m 
a n o pe n-la b el st u d y ( St u d y 1 1 2 9; N C T 0 2 1 9 5 8 6 9) of 4 2 s u bjects wit h c G V H D w h o ha d faile d 
first-li ne c ortic oster oi d t h era p y a n d re q uir e d a d diti o nal t hera p y.7 
1. 2  R h o -A ss oci ate d P r otei n  K i n ases  
R h o -ass ociate d c oile d -c oil ki nases ( R O C Ks) pla y a ce ntr al r ole i n t he c o ntr ol of acti n 
c yt os kel et o n asse m bl y a n d cell ular f u ncti o ns, s uc h as pr oliferati o n, a d hesi o n, mi grati o n a n d 
p ha g o c yt osis. 8 ,9 ,1 0 ,1 1 T w o is of or ms of R O C K ha ve bee n i de ntifie d, R O C K 1 a n d R O C K 2, w hic h  
are acti vate d b y R h o G T Pases a n d pr o m ote acti n -m y osi n me diate d c o ntractile f orce ge nerati o n 
via seri ne -t hr e o ni ne ph os p h or ylati o n o f n u m er o us d o w nstrea m tar gets.  D uri n g t he i m m u ne 
res p o nse, R O C K si g nali n g is critic al i n t he c o or di nati o n a n d bala nci n g of T-cell -me diate d 
i m m u ne res p o nses, i ncl u di n g cell ular m o ve me nt, T-cell rece pt or ( T C R) si g nali n g a n d t h e 
ac q uisiti o n of t he a p pr o priat e T-cell effect or pr o gra m. 1 2 ,1 3    H o we ver, o nl y t he R O C K 2 is of or m 
was s h o w n t o be p h ysi ol o gic all y acti vate d i n C D 4 + T cells u n der T h el per 1 7 ( T H 1 7) s ke wi n g, 
lea di n g t o i ncreas e d secreti o n of i nterle u ki n- (I L-)1 7 a n d I L -2 1 i n b ot h mice a n d h u ma ns. 1 4 ,1 5  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
M ore o ver, tar get e d R O C K 2 i n hi biti o n effecti vel y decrease d I L -1 7 pr o d u cti o n i n vi v o a n d 
a meli orate d t he s p o nta n e o us de vel o p me nt of art hritis, dia betes a n d l u p us i n mice.1 5  A d diti o nall y, 
R h o -ass ociate d pr otei n ki nase ( R O C K ) acti vit y was i ncrease d i n p atie nts wit h r he u mat oi d 
art hritis  a n d s yste mic l u p us er yt h e mat os us.1 4 ,1 6 ,1 7  T he s pecific i n hi biti o n of R O C K 2 t heref ore 
has be e n e x a mi ne d f or its p ote ntial as a t hera p y f or a ut oi m m u ne dis or ders.  
1. 3  N o n -cli nic al B ac k gr o u n d of Bel u m os u dil   
Bel u m os u dil  is a n orall y a vaila ble R O C K 2 selecti ve i n hi bit or.  Data fr o m a P hase  1 cli nical trial 
de m o nstrate d  t hat oral a d mi nistrati o n of bel u m os u dil  to healt h y h u ma n s u bj ects d o w n -re g ulates 
t he a bilit y of T cells t o secrete I L-2 1 a n d I L -1 7, b ut n ot i nterfer o n - i n r es p o nse t o T C R 
sti m ulati o n e x vi v o.  Treat me nt wit h bel u m os u dil als o pr o m otes t he s u p pressi ve f u ncti o n of 
re g ulat or y T cells t hr o u g h u p-re g ulati o n of S T A T 5 p h os p h or ylati o n a n d p ositi ve re g ul ati o n of 
F o x p 3 e x pressi o n .1 8 
C hr o nic G V H D re mai ns a maj or c o m plicati o n f oll o wi n g all o ge n eic b o ne m arr o w 
tra ns pla ntati o n. 1 9  T he u n derl yi n g p at h o ge nesis of G V H D is si milar t o a ut oi m m u ne attac k i n a 
n u m ber of res p ects, i ncl u di n g a c o ntri b ut or y r ole of pr o -i nfla m mat or y T H 1 7 a n d T f ollic ular 
hel per ( T F H) cells a n d a pr otecti ve r ole of T  re g ul at or y cells.2 0  I n a d diti o n, t he a berra nt 
acti vati o n of i m m u ne cel ls lea ds t o i ncreas e d secreti o n of tra nsf or mi n g gr o wt h fact or- w hic h 
pr o m otes fi br o blast acti v ati o n, c olla ge n pr o d ucti o n , a n d de vel o p me nt of tiss ue fi br osis .2 1  
Bel u m os u d il effecti vel y a meli orates c G V H D i n m ulti ple m o dels: a f ull maj or hist oc o m pati bilit y 
c o m ple x (M H C )-mis matc h m o del of br o nc hi olitis o blitera ns s y n dr o me t hat i n v ol ve d a wi de 
s pectr u m of tar get or ga ns i ncl u di n g l u n g a n d li ver 2 2 as well as a mi n or M H C -mis matc h m o del of 
scler o der m at o us G V H D. 2 3  Treat me nt wit h bel u m os u dil  res ulte d i n n or malizati o n of pat h o ge nic 
p ul m o nar y f u ncti o n, w hi c h c orrelates wit h a mar ke d re d ucti o n of a nti b o d y a n d c olla ge n 
de p ositi o n i n t he l u n gs of treate d mice t o le vels c o m para ble t o n o n -c G V H D c o ntr ols. 2 4  S plee ns 
of mice treate d wit h bel u m os u dil ha d decrease d fre q ue nc y of T F H a n d i ncrease d fre q ue n c y of T 
f ollic ular re g ulat or y cells, acc o m pa ni e d b y a re d ucti o n i n S T A T 3 a n d c o nc urre nt i ncrease i n 
S T A T 5 p h os p h or ylati o n. To get her t hese d ata hi g hli g ht t he p ote ntial of tar gete d R O C K 2 
i n hi biti o n f or c G V H D t h era p y. 
R efer t o t he Bel u m os u dil  I n v esti gat or’s Br oc h ure (I B)  f or m or e detaile d i nf or mati o n. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 1 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1. 4  Cli nic al B ac k gr o u n d of Bel u m os u dil   
Bel u m os u dil  was well t olerate d i n P hase  1 st u dies of healt h y v ol u nteers at si n gle d oses u p t o 
1 0 0 0  m g, a n d wit h r e peat d oses u p t o 5 0 0  m g t wice dail y ( BI D ) f or 2 8 da ys. 
A d mi nistrati o n of bel u m os u dil  2 0 0  m g ta blet s i n t he fe d state res ulte d i n an a p pr o xi mate 2 -f ol d 
i ncreas e d e x p os ure i n ter ms of ma xi m u m c o nce ntrati o n ( C ma x ) a n d area u n der t he c o n ce ntr ati o n -
ti me c ur ve (A U C ) w he n c o m pare d t o t he fas te d st ate.  P har mac o ki n etic  ( P K) a nal yses s h o w e d 
t hat bel u m os u dil  a d mi nistere d as a 2 0 0  m g t a blet i n t he fe d state  was ra pi dl y a bs or be d wit h a  
me dia n  ti me of ma xi m u m c o nce ntrati o n of a p pr o xi matel y 3  h o urs.  Eli mi nati o n half -life is 
a p pr o xi matel y 7 h o urs .  Varia bilit y i n e x p os ure relate d para m eters C ma x  a n d A U C was re d uce d 
w he n bel u m os u dil  was a d mi nistere d i n t he fe d state w he n c o m pare d t o t he faste d state.  
Bel u m os u dil  s h o ul d be ta ke n wit h f o o d. 
Data fr o m St u d y K D 0 2 5 -2 0 8  a n d St u d y K D 0 2 5 -2 1 3  i n s u bjects wit h c G V H D are s u m marize d i n 
S ecti o n 1. 4. 1  a n d Secti o n  1. 4. 2 , res pecti vel y. 
R efer t o t he Bel u m os u dil  I B f or m ore d etaile d i nf or mati o n. 
1. 4. 1  
St u d y K D 0 2 5 -2 0 8   
Details of t he o bjecti ve, desi g n, efficac y res ults, a n d safet y res ults are a v aila ble i n t he 
St u d y  K D 0 2 5 -2 0 8 C li nic al S t u d y R e p ort ( C S R) , 0 7 J ul y 2 0 2 0 a n d are s u m marize d bel o w.  
O bjecti ves:  
T he pri mar y o bje cti ves of St u d y K D 0 2 5 -2 0 8 were t o e val uate t he acti vit y of bel u m os u dil i n 
s u bjects wit h ster oi d-de p e n de nt c G V H D a n d acti v e disease i n ter ms of p artial res p o nse ( P R) a n d 
c o m plete res p o nse ( C R) ; a n d safet y a n d t olera bilit y of bel u m os u dil i n s u bjects wit h c G V H D. 
I n cl usi o n/ E x cl usi o n Criteria: 
T he maj or i ncl usi o n criteria were: ( 1) mal e  a n d fe male s u bjects ≥ 1 8 years of a ge wit h all o ge n eic 
b o ne marr o w tra ns pla nt or H C T ; ( 2) recei vi n g gl u c oc ortic oi d t hera p y a n d calci ne uri n t hera p y or 
gl uc o c ortic oi d t hera p y al o n g f or c G V H D; ( 3) p ersiste nt acti ve c G V H D ma nifestati o ns ; 
( 4) ≤ 3  pri or li nes of treat me nt f or c G V H D; a n d ( 5) Kar n ofs k y Perf or m a nce Scale  ( K P S) sc ore 
>  4 0.  Details of i ncl usi o n criteria are pr ovi de d i n t he K D 0 2 5 -2 0 8 Pr ot oc ol, Secti o n 7. 2 . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
T he  maj or e x cl usi o n criteria were: ( 1) recei vi n g a n i n vesti gati o nal G V H D treat me nt wit hi n 
2 8  da ys of st u d y e ntr y; ( 2) ac ute G V H D; ( 3) ta ki n g ot her i m m u n os u p pressa nt dr u gs f or G V H D 
i ncl u di n g ma m malia n  tar get of ra p a m yci n ( m T O R) i n hi bit ors; a n d ( 4) ta ki n g a n y m e dicati o n 
k n o w n t o be a m o derate or str o n g i n hi bit or of t he C Y P 3 A 4  is oz y me or a n y dr u gs k n o w n t o b e 
m o derate or str o n g C Y P 3 A 4 i n hi bit ors.  Details of e x cl usi o n criteria are pr o vi de d i n t he 
K D 0 2 5 -2 0 8 Pr ot oc ol, Secti o n  7. 2 . 
St u d y Desi g n  
St u d y K D 0 2 5 -2 0 8 w as a P hase 2a, o pe n -l a bel, d os e-escalati o n, safet y, t olera bilit y, a n d acti vit y 
st u d y of bel u m os u dil i n s u bjects wit h c G V H D.  A p pr o xi matel y 4 8 s u bjects were t o be e nr olle d t o 
recei v e oral b el u m os u dil i n 3 c o h orts, eac h c o h ort c o nsisti n g of 1 6 s u bject s ( 1: 1: 1 fas hi o n): 
b el u m os u dil 2 0 0 m g Q D ( C o h ort 1); b el u m os u dil 2 0 0 m g BI D ( C o h ort 2); a n d b el u m os u dil 4 0 0 
m g Q D ( C o h ort 3).  Bel u m os u dil was t o be a d mi nistere d i n 2 8 -da y c ycles u ntil disease 
pr o gressi o n or u nacce pta ble t o xicit y.  
Efficac y assess me nts i ncl u de d usi n g t he criteria of 2 0 1 4 NI H C o nse ns us De vel o p me nt Pr oject o n 
Cli nical Trials i n c G V H D  res p o nse ( C R, P R, or lac k of res p o nse [u nc ha n ge d, mi x e d, or 
pr o gressi o n ]), c G V H D se verit y (cli nical-re p orte d) a n d s y m pt o m (s u bject-re p orte d), a n d Lee 
c G V H D S y m pt o m Scale ( L S S).  
Safet y assess me nts i ncl u d e d p h ysi cal e xa mi nati o ns ( P Es); vital si g n meas ure me nts; bl o o d 
sa m ple c ollecti o n f or he mat ol o g y a n d c he mistr y; uri nal ysis; electr ocar di o gra ms  ( E C Gs); a d v erse 
e ve nt (A E ) assess me nts; c o nc o mita nt me dicati o n assess me nts ; a n d pre g n a nc y t esti n g f or fe m ales 
of c hil d beari n g p ote ntial.  
A F oll o w -u p Safet y Visit occ urre d 2 8 da ys ( ± 7 d a ys) after t h e last d ose of st u d y dr u g.  
S u bjects were c o ntacte d a p pr o xi matel y e ver y 8 wee ks via tele p h o n e, e mail, or p ostal mail t o 
c o nfir m s ur vi val stat us a n d t he i nitiati o n of a n y a nti-ca ncer treat me nt or a n y c h a n ges i n treat me nt 
of c G V H D . 
Dis p ositi o n of S u bjects  
O verall, 6 4 s u bjects w ere scree n e d f or t h e st u d y  of w h o m 5 4 were i n cl u de d i n t he m o difie d 
I nte nt-t o-Treat ( mI T T ) P o p ulati o n: 1 7 s u bjects i n C o h ort 1, 1 6 s u bjects i n C o h ort 2, a n d 
2 1  s u bjects i n C o h ort 3.  As of t he c ut-off date f or t his a nal ysis ( 1 9 Fe br uar y 2 0 2 0), 4 7 ( 8 7. 0 %) 
s u bjects ha ve disc o nti n ue d treat me nt a n d 7 ( 1 3. 0 %) s u bjects re mai n o n tr eat me nt wit h 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
bel u m os u dil.  T he m ost f re q ue nt r eas o n f or treat m e nt disc o nti n uati o n was disease pr o gressi o n 
( 2 2 [ 4 0. 7 %] s u bjects).  A t otal of 3 7 ( 6 8. 5 %) s u bjects were p artici pati n g i n t he st u d y, eit her bei n g 
acti vel y treat e d wit h bel u m os u dil or bei n g f oll o we d f or s ur vi val (i n L o n g -ter m F oll o w -U p).  
Se ve ntee n ( 3 1. 5 %) s u bjects ha ve disc o nti n ue d fr o m t he st u d y f or t he f oll o wi n g reas o ns: 
1 1  ( 2 0. 4 %) s u bjects die d, 5 ( 9. 3 %) s u bjects w ere l ost t o f oll o w-u p, a n d 1 ( 1. 9 %) s u bject 
disc o nti n ue d f or ot her reas o ns.  T he o verall me dia n f oll o w -u p d urati o n was  2 8. 8 m o nt hs: 
3 5. 9  m o nt hs f or C o h ort 1 ; 3 2. 4 m o nt hs f or C o h ort 2 ; a n d 2 4. 0 m o nt hs f or C o h ort 3.  
De m o gra p hics a n d Baseli ne C haract eristics  
O verall, s u bjects ha d a m e dia n a ge of 5 1. 5 years , were pre d o mi na ntl y male ( 3 4 [ 6 3. 0 %]) , a n d 
W hite ( 4 7 [ 8 7. 0 %]).  T hirt y -ni n e  ( 7 2. 2 %) s u bjects ha d a K P S sc ore ≥ 8 0.   M ost s u bjects ha d n o 
pre vi o us a ut ol o g o us tra ns pla nts ( 4 5 [ 8 3. 3 %] s u bjects) ; all ha d recei ve d a pre vi o us all o ge n eic 
tra ns pla nt.  T he me dia n ti me t o c G V H D dia g n osis fr o m tra ns pla nt was 7. 9  m o nt hs.  T he me di a n 
ti me fr o m c G V H D di a g n osis t o st u d y e nr oll me nt was 2 0. 0 m o nt hs. 
T he o verall me dia n n u m ber of pri or li nes of s yst e mic c G V H D t hera p y was 2. 0.   
T hirt y -fi ve ( 7 2. 9 %) s u bjects were refract or y t o t h e last s yste mic c G V H D treat me nt pri or t o 
e nr oll me nt i n t he st u d y.   All s u bjects ha d recei ve d c o nc o mita nt c ortic oster oi d me dicati o n at st u d y 
i nitiati o n; ot her c o m m o n c o nc o mita nt me dicati o ns recei v e d at Baseli ne  were C NI ( 2 3  s u bjects, 
4 2. 6 %), a n d e xtrac or p oreal p h ot o p h eresis (E C P ; 1 2 s u bjects, 2 2. 2 %).  
Efficac y  
T he p ri mar y efficac y e n d p oi nts are pres e nte d i n  Ta ble 1 .   
T he O R R was 6 4. 8 % ( 9 5 %  c o nfi de n ce i nter val [ CI ]: 5 0. 6 %, 7 7. 3 %) acr oss all 3 c o h orts:  
6 4. 7 %  ( 9 5 % CI: 3 8. 3 %, 8 5. 8 %) i n C o h ort 1 ; 6 8. 8 % ( 9 5 % CI: 4 1. 3 %, 8 9. 0 %) i n C o h ort 2 ; a n d 
6 1. 9 % ( 9 5 % CI: 3 8. 4 %, 8 1. 9 %) i n C o h ort 3.  All res p o nses were P Rs.  T he l o wer b o u n d of t he 
9 5 % CI ar o u n d t he O R R e x cee de d 3 0 % o v erall a n d f or eac h c o h ort.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
Ta ble 1 . 
Pri m ar y Effic ac y E n d p oi nt Res ults fr o m St u d y K D 0 2 5 -2 0 8  
Pri m ar y Effic ac y O utc o me s 
C o h ort 1  
2 0 0 m g Q D  
 N  =  1 7  
C o h ort 2  
2 0 0 m g BI D  
 N  =  1 6  
C o h ort 3  
4 0 0 m g Q D  
 N  =  2 1  
 
O ver all  
 N  =  5 4  
O R R  ( C R or  P R)  - n  ( %) 
1 1  ( 6 4. 7) 
1 1  ( 6 8. 8) 
1 3  ( 6 1. 9) 
3 5  ( 6 4. 8) 
9 5 %  CI of O R R  
( 3 8. 3, 8 5. 8) 
( 4 1. 3, 8 9. 0) 
( 3 8. 4, 8 1. 9) 
( 5 0. 6, 7 7. 3)  
B est res p o nse  
C R  
0  ( 0) 
0  ( 0) 
0  ( 0) 
0  ( 0) 
P R  
1 1  ( 6 4. 7) 
1 1  ( 6 8. 8) 
1 3  ( 6 1. 9) 
3 5  ( 6 4. 8) 
L R  
L R -U nc ha n ge d  
2  ( 1 1. 8) 
3  ( 1 8. 8) 
4  ( 1 9. 0) 
9  ( 1 6. 7) 
L R -Mi xe d  
3  ( 1 7. 6) 
1  ( 6. 3) 
0  ( 0) 
4  ( 7. 4) 
L R -P r o gressi o n 
1  ( 5. 9) 
0  ( 0) 
1  ( 4. 8) 
2  ( 3. 7) 
N o  res p o nse assess me nt  
0  ( 0) 
1  ( 6. 3) 
3  ( 1 4. 3) 
4  ( 7. 4) 
BI D =  t wice dail y; CI  =  c o nfi de nce  i nter val; C R  =  c o m plete res p o nse;  L R  =  Lac k  of  Res p o nse; mI T T  =  m o difie d  I nte nt-t o-Treat;  
NI H  =  Nati o nal I nstit utes  of Healt h; O R R =  O verall Res p o nse  Rate; P R  =  partial  res p o nse; Q D =  o nce  dail y.  
N ote:  mI T T P o p ulati o n . 
N ote:  T he perce nta ges were calc ulate d base d o n t he n u m ber of s u bjects i n t he mI T T P o p ulati o n  
 
Safet y  
T he me dia n d urati o n of treat me nt o verall was 8. 4 m o nt hs: 8. 5 m o nt hs f or C o h ort 1 ; 7. 5 m o nt hs 
f or C o h ort 2; a n d 9. 0 m o nt hs f or C o h ort 3.  O verall, 4 2. 6 % of s u bjects recei ve d > 1 2 m o nt hs of 
bel u m os u dil treat me nt.  T he me dia n relati ve d ose i nte nsit y was 9 8. 3 %: 9 9. 1 % f or C o h ort 1 ; 
9 6. 6 % f or C o h ort 2 ; a n d 9 9. 1 % f or C o h ort 3.  
Safet y res ults are pres e nte d i n  Ta ble 2 . 
I n t otal, 1 8 ( 3 3. 3 %) s u bjects e x perie nce d a treat me nt-e mer ge nt A E ( T E A E ) lea di n g t o 
disc o nti n ua ti o n of treat me nt: 6  ( 3 5. 3 %) s u bjects i n C o h ort 1; 5  ( 3 1. 3 %) s u bjects i n C o h ort 2; a n d 
7  ( 3 3. 3 %) s u bjects i n C o h ort 3.  T w o s u bjects disc o nti n ue d bel u m os u dil treat me nt f or A Es 
c o nsi dere d pr o ba bl y rel ate d t o bel u m os u dil: 1 s u bject i n C o h ort 1 ( hea d ac h e  a n d diarr hea ) a n d 
1  s u bject i n C o h ort 3 (fati g ue).  O verall, 1 1 s u bjects e x perie nce d a seri o us T E A E  ( S A E) t hat le d 
t o disc o nti n uati o n of treat me nt: 3 s u bjects i n C o h ort 1; 2 s u bjects i n C o h ort 2 ; a n d 6 s u bjects i n 
C o h ort 3 .  No ne of t hese seri o us S A Es  were c o nsi dere d relate d t o bel u m os u dil.   I n C o h ort 3, 
4  ( 1 9. 0 %) s u bjects e x perie nce d a S A E  t hat le d t o deat h.  Ho we v er , n o n e were c o nsi dere d relat e d 
t o bel u m os u dil .  N o s u bjects die d i n C o h orts 1 or 2 d ue t o a S A E . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Ta ble 2 . 
S afet y Re s ults fr o m St u d y K D 0 2 5-2 0 8  
S afet y O utc o mes  
C o h ort 1  
2 0 0 m g Q D  
N  =  1 7  
n ( %) 
C o h ort 2  
2 0 0 m g BI D  
N  =  1 6  
n ( %) 
C o h ort 3  
4 0 0 m g Q D  
N  =  2 1  
n ( %) 
 
O ver all  
N  =  5 4  
n ( %) 
S u bj ects  wit h at least 1  T E A E  
1 7  ( 1 0 0) 
1 6  ( 1 0 0) 
2 0  ( 9 5. 2) 
5 3  ( 9 8. 1) 
 
S u bj ects  wit h  T E A Es b y  ma xi m u m  se verit y 
   Gra de 3:  S e vere 
8  ( 4 7. 1) 
8  ( 5 0. 0) 
6  ( 2 8. 6) 
2 2  ( 4 0. 7) 
   Gra de 4:  L ife-t hreate ni n g 
1  ( 5. 9) 
2  ( 1 2. 5) 
4  ( 1 9. 0) 
7  ( 1 3. 0) 
   Gra de 5:  F atal 
0  ( 0) 
0  ( 0) 
4  ( 1 9. 0) 
4  ( 7. 4) 
T E A Es  b y P T  occ urri n g i n  >  2 0 %  s u bjects o verall 
   U p per  res pirat or y tract i nfecti o n 
9  ( 5 2. 9) 
9  ( 5 6. 3) 
7  ( 3 3. 3) 
2 5  ( 4 6. 3) 
   Diarr hea  
6  ( 3 5. 3) 
5  ( 3 1. 3) 
7  ( 3 3. 3) 
1 8  ( 3 3. 3) 
   Na usea  
6  ( 3 5. 3) 
4  ( 2 5. 0) 
8  ( 3 8. 1) 
1 8  ( 3 3. 3) 
   Fati g ue  
6  ( 3 5. 5) 
3  ( 1 8. 8) 
9  ( 4 2. 9) 
1 8  ( 3 3. 3) 
   D ys p nea  
3  ( 1 7. 6) 
6  ( 3 7. 5) 
7  ( 3 3. 3) 
1 6  ( 2 9. 6) 
   Hea dac he  
4  ( 2 3. 5) 
3  ( 1 8. 8) 
6  ( 2 8. 6) 
1 3  ( 2 4. 1) 
   E de ma peri p heral  
3  ( 1 7. 6) 
4  ( 2 5. 0) 
6  ( 2 8. 6) 
1 3  ( 2 4. 1) 
   C o u g h  
1  ( 5. 9) 
4  ( 2 5. 0) 
7  ( 3 3. 3) 
1 2  ( 2 2. 2) 
   H y perte nsi o n  
5  ( 2 9. 4) 
2  ( 1 2. 5) 
4  ( 1 9. 0) 
1 1  ( 2 0. 4) 
 
 
 
 
 
S u bj ects  wit h ≥ 1  st u d y 
dr u g -relate d T E A E  
8  ( 4 7. 1) 
8  ( 5 0. 0) 
1 4  ( 6 6. 7) 
3 0  ( 5 5. 6) 
St u d y dr u g -relate d T E A Es b y P T  occ urri n g  i n >  1 0 % of  s u bjects o verall  
   Fati g ue  
1  ( 5. 9) 
2  ( 1 2. 5) 
3  ( 1 4. 3) 
6  ( 1 1. 1) 
   Na usea  
2  ( 1 1. 8) 
1  ( 6. 3) 
3  ( 1 4. 3) 
6  ( 1 1. 1) 
 
 
 
 
 
S u bj ects  wit h at least 1  Gra de  3  T E A E  
9  ( 5 2. 9) 
1 0  ( 6 2. 5) 
1 4  ( 6 6. 7) 
3 3  ( 6 1. 1) 
Gra de  3  T E A Es  b y P T  occ urri n g  i n  5 % of  s u bj ects o verall 
   D ys p nea  
1  ( 5. 9) 
2  ( 1 2. 5) 
4  ( 1 9. 0) 
7  ( 1 3. 0) 
   G G T  i ncrease d 
2  ( 1 1. 8) 
2  ( 1 2. 5) 
0  ( 0) 
4  ( 7. 4) 
   H y per gl yce mia  
2  ( 1 1. 8) 
0  ( 0) 
2  ( 9. 5) 
4  ( 7. 4) 
   H y p o xia  
1  ( 5. 9) 
1  ( 6. 3) 
2  ( 9. 5) 
4  ( 7. 4) 
   A ne mia  
2  ( 1 1. 8) 
1  ( 6. 3) 
0  ( 0) 
3  ( 5. 6) 
   L u n g i nfecti o n  
0  ( 0) 
1  ( 6. 3) 
2  ( 9. 5) 
3  ( 5. 6) 
S u bj ects  wit h ≥ 1  st u d y dr u g -
relate d Gra de  3  T E A E  
1  ( 5. 9) 
3  ( 1 8. 8) 
2  ( 9. 5) 
6  ( 1 1. 1) 
St u d y dr u g -relate d Gra de   3  T E A Es b y P T  occ urri n g i n  >  3 %  if s u bjects o verall 
   A L T i ncrease d 
1  ( 5. 9) 
1  ( 6. 3) 
0  ( 0) 
2  ( 3. 7) 
   A S T i ncrease d 
1  ( 5. 9) 
1  ( 6. 3) 
0  ( 0) 
2  ( 3. 7) 
 
 
 
 
 
S u bj ects  wit h at least 1  S A E  
5  ( 2 9. 4) 
6  ( 3 7. 5) 
1 2  ( 5 7. 1) 
2 3  ( 4 2. 6) 
S A Es  b y  P T occ urri n g i n  >  2 % s u bjects o verall  
   D ys p nea  
0  ( 0) 
1  ( 6. 3) 
3  ( 1 4. 3) 
4  ( 7. 4) 
   L u n g i nfecti o n  
0  ( 0) 
1  ( 6. 3) 
2  ( 9. 5) 
3  ( 5. 6) 
   H y p o xia  
0  ( 0) 
0  ( 0) 
2  ( 9. 5) 
2  ( 3. 7) 
   I nfl ue nza-li ke ill ness 
0  ( 0) 
0  ( 0) 
2  ( 9. 5) 
2  ( 3. 7) 
 
 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S afet y O utc o mes  
C o h ort 1  
2 0 0 m g Q D  
N  =  1 7  
n ( %) 
C o h ort 2  
2 0 0 m g BI D  
N  =  1 6  
n ( %) 
C o h ort 3  
4 0 0 m g Q D  
N  =  2 1  
n ( %) 
 
O ver all  
N  =  5 4  
n ( %) 
S u bj ects wit h T E A E lea di n g t o d ose 
disc o nti n uati o n  
6 ( 3 5. 3)  
5 ( 3 1. 3)  
7 ( 3 3. 3)  
1 8 ( 3 3. 3)  
 
 
 
 
 
S u bj ects wit h a st u d y dr u g -relate d T E A E 
lea di n g t o d ose disc o nti n uati o n 
2 ( 1 1. 8)  
0  
1 ( 4. 8)  
3 ( 5. 6)  
 
 
 
 
 
S u bj ects wit h T E A E lea di n g t o deat h  
0  
0  
4 ( 1 9. 0)  
4 ( 7. 4)  
A L T  =  ala ni ne a mi n otra nsferase; A S T  =  as partate a mi n otra nsferase;  BI D =  t wice dail y; G G T =  ga m ma  gl uta m yl tra nsferase ; 
Me d D R A  =  Me dical  Dicti o nar y f or Re g ulat or y  Acti vities; P T  =  preferr e d  ter m; Q D  =  o nce  dail y;  S A E = seri o us 
(treat me nt-e mer ge nt a d verse e ve nt); T E A E = treat me nt-e mer ge nt a d verse  e ve nt. 
N ote:  Safet y P o p ulati o n  
 
 
C o ncl usi o ns  
I n t his hea vil y pre-tr eate d p o p ulati o n wit h acti ve c G V H D, b el u m os u dil de m o nstrate d cli nical 
acti vit y a n d a treat me nt effect at all 3 d ose le vels wit h c o nsiste nt res p o nse rates o verall as well as 
i n s u b gr o u p p o p ulati o ns.  N ot o nl y di d bel u m os u dil s h o w hi g h perce nta ge of o verall res p o nse, 
b ut t he res p o nses were cli nicall y mea ni n gf ul, d ura ble, a n d ass ociat e d wit h i m pr o ve me nt i n 
meas ures of s y m pt o m sc ore a n d re d ucti o n i n c orti c oster oi d d ose.   Wit h a me dia n f oll o w -u p 
d urati o n of 2 9 m o nt hs, t hese res ults s u g gest a fa v ora ble be n efit/ris k pr ofile wit h bel u m os u dil f or 
t he treat me nt of s u bje cts wit h c G V H D after 1 t o 3 li nes of pri or t hera p y. 
1. 4. 2  
St u d y K D 0 2 5 -2 1 3   
Details of t he o bjecti ve, desi g n, efficac y res ults, a n d safet y res ults are a v aila ble i n t he 
St u d y  K D 0 2 5 -2 1 3 C S R , 1 6 J ul y 2 0 2 0 , a n d are s u m marize d bel o w. 
O bjecti ves  
T he o bjecti ve of St u d y K D 0 2 5 -2 1 3 was t o e v al uat e t he efficac y a n d safet y of bel u m os u dil at 
d ose le vels of 2 0 0 m g Q D  a n d 2 0 0 m g BI D i n s u bjects wit h c G V H D w h o ha d pre vi o usl y bee n 
treate d wit h at least 2 pri or li nes of s yst e mic t hera p y. 
I n cl usi o n/ E x cl usi o n Criteria 
T he maj or i ncl usi o n criteria were: ( 1) ≥ 1 2 years of a ge w h o ha d all o ge nei c H C T ; ( 2) pre vi o usl y 
recei v e d at least 2 a n d n ot m ore t ha n 5 li nes of s yste mic t hera p y f or c G V H D; ( 3) recei ve d 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
gl uc o c ortic oi d t hera p y wit h a sta ble d ose of t he 2 wee ks pri or t o scree ni n g; a n d ( 4) ha d p ersiste nt 
c G V H D ma nifestati o ns s uc h t hat s yste mic t h era p y was i n dicate d.  Details of i n cl usi o n criteria 
are pr o vi d e d i n t he K D 0 2 5 -2 1 3 Pr ot oc ol, Secti o n 4. 3 . 
T he maj or e x cl usi o n criteria were: ( 1) n ot bee n o n a sta ble d ose/re gi me n of s yste mic c G V H D 
treat me nts f or at least 2 wee ks pri or t o scree ni n g; ( 2) hist ol o gic rela pse of t he u n derl yi n g ca n cer 
or p ost -tra ns pla nt l y m p h o pr oliferati ve dise ase at t he ti me of scree ni n g; a n d (3 ) 3 0 c urre nt 
treat me nts wit h i br uti ni b ( pri or treat me nt wit h i br uti ni b was per mitte d wit h a was h o ut of 
≥ 2 8  da ys pri or t o ra n d o mizati o n ).  Details of e x cl usi o n criteria are pr o vi d e d i n t he 
St u d y  K D 0 2 5 -2 1 3 Pr ot oc ol, Secti o n  4. 4 . 
St u d y Desi g n  
St u d y K D 0 2 5 -2 1 3 w as a n o pe n -la bel, r a n d o mize d, m ultice nter st u d y i n s u bjects ≥ 1 2 years of 
a ge wit h c G V H D w h o ha d pre vi o usl y b ee n treate d wit h ≥ 2 pri or li nes of s yste mic t hera p y.  
I n t he ori gi nal pr ot oc ol, after a 2-wee k s cree ni n g p eri o d, 1 2 6 s u bjects wit h acti ve c G V H D were 
t o be ra n d o mize d i n a 1: 1 fas hi o n t o recei ve 1 of 2 treat me nt re gi me ns wit h bel u m os u dil:  
•  Ar m A:  Bel u m os u dil 2 0 0 m g Q D  
•  Ar m B:  Bel u m os u dil 2 0 0 m g BI D  
H o we ver, wit h A me n d m e nt 2, t he sa m ple siz e was i ncrease d wit h 2 0 a d diti o nal a d olesce nt 
s u bjects a n d 2 0 a d ult s u bjects i nt o a site -s pecific C o m pa ni o n St ud y t o c oll ect bi os peci me ns.  
T hese a d diti o nal 4 0 s u bjects were als o be ra n d o mize d  i n a 1: 1  fas hi o n t o Ar m A or Ar m B.  
Ra n d o mizati o n was stratifie d acc or di n g t o pri or c G V H D treat me nt wit h i br uti ni b ( Yes/ N o) a n d 
se vere c G V H D at Baseli ne  ( Yes/ N o). 
S u bjects r ecei v ed  2 8 -da y treat me nt c ycl es u ntil cli nicall y si g nifica nt pr o gressi o n of c G V H D.  
S u bjects w h o di d n ot ac hie ve d a res p o nse after 1 2 c ycles of b el u m os u dil were wit h dra w n if , i n 
t he I n v esti gat or’s j u d g me nt, t here was n o e vi de nce of cli nical be nefit.  After treat me nt was 
st o p pe d, s u bjects ha d a 4 -wee k F oll o w -u p V isit. 
T he pri mar y e n d p oi nt w as t he O R R, wit h res p o nses as defi ne d b y t he 2 0 1 4 NI H C o nse ns us 
De vel o p me nt Pr oject o n cli nical trials i n c G V H D.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Dis p ositi o n of S u bjects  
O verall, 1 3 2 s u bjects recei ve d at least 1 d ose of bel u m os u dil: 6 6 s u bjects i n Ar m A a n d 
6 6  s u bjects i n Ar m B. 
As of t he c ut off date , 1 9 Fe br uar y 2 0 2 0, t he me di a n f oll o w -u p d urati o n was 7. 9  m o nt hs: 
8. 0  m o nt hs f or Ar m A a n d 7. 9 m o nt hs f or Ar m B.  I n t otal, 6 2 ( 4 7. 0 %) s u bj ects ha d  disc o nti n ue d 
fr o m treat me nt; 7 0 ( 5 3. 0 %) re mai n o n tr eat me nt wit h bel u m os u dil.  T he m ost fre q ue nt reas o ns 
f or treat me nt disc o nti n uati o n were pr o gressi o n of c G V H D ( 1 6 [ 1 2. 1 %] s u bjects) a n d wit h dra wal 
b y s u bject ( 1 4 [ 1 0. 6 %]).  A t otal of 1 1 9 ( 9 0. 2 %) s u bjects  partici pate d  i n t he st u d y, eit her acti vel y 
treate d wit h bel u m os u dil or f oll o we d f or s ur vi val.  T hirtee n ( 9. 8 %) s u bjects ha d  disc o nti n ue d 
fr o m t he st u d y: 8 ( 6. 1 %) s u bjects die d; 3  ( 2. 3 %) s u bjects wit h dre w; 1 ( 0. 8 %) s u bject l ost t o 
f oll o w-u p ; a n d 1 ( 0. 8 %) s u bject  f or w hic h d ata was missi n g. 
De m o gra p hic a n d Baseli ne C haracteristics  
O verall, s u bjects ha d a m e dia n a ge of 5 5. 5 years a n d were pre d o mi na ntl y male ( 7 5 [ 5 6. 8 %] 
s u bjects), W hite ( 1 1 2 [ 8 4. 8 %] s u bjects), a n d n ot His pa nic or Lati n o ( 1 1 0 [ 8 3. 3 %] s u bjects).   I n 
t otal, 1 0 3 ( 7 8. 0 %) s u bjects ha d a K P S  ≥ 8 0.  
All s u bjects ha d recei ve d a pre vi o us all o ge n eic tra ns pla nt.  T he m ost fre q ue nt i n dicati o n s f or t he 
m ost rece nt tra ns pla nt r ecei ve d b y s u bjects i ncl u d e d ac ute m yel o ge n o us le u ke mia ( 5 3 [ 4 0. 2 %] 
s u bjects), ac ute l y m p h o blastic le u ke mia ( 1 9 [ 1 4. 4 %] s u bjects), ot her ( 1 8 [ 1 3. 6 %] s u bjects), a n d 
m yel o d ys plastic  s y n dr o me ( 1 3 [ 9. 8 %] s u bjects).  T he maj orit y of s u bjects ha d pri or ac ute G V H D  
( 9 3 [ 7 0. 5 %] s u bjects): 4 2 ( 6 3. 6 %) s u bjects i n Ar m A a n d 5 1 ( 7 7. 3 %) s u bjects i n Ar m  B.  T h e 
me dia n ti me t o c G V H D dia g n osis fr o m t he m ost rece nt tra ns pl a nt was 6. 8 m o nt hs.  T he me dia n 
ti me fr o m c G V H D di a g n osis t o st u d y e nr oll me nt was 2 8. 9 m o nt hs: 2 5. 2 m o nt hs i n Ar m A a n d 
3 0. 2  m o nt hs i n Ar m B.   T he o verall me dia n n u m ber of pri or li nes of s yst e mic c G V H D t hera p y 
was 3. 0  f or Ar m A a n d 4. 0 f or Ar m B.  O verall , 7 9 ( 7 2. 5 %) s u bjects wit h k n o w n stat us were 
refract or y t o t he last s yst e mic c G V H D treat me nt pri or t o e nr oll me nt i n t he st u d y (sta ble dise ase 
or pr o gressi ve dise ase ): 4 5 ( 8 0. 4 %) s u bjects i n Ar m A a n d 3 4 ( 6 4. 2 %) s u bj ects i n Ar m B.   All 
s u bjects were t a ki n g a c o nc o mita nt c G V H D me di cati o n, m ost fre q ue ntl y pre d nis o ne 
( 1 2 8 [ 9 7. 0 %] s u bjects), tacr oli m us ( 4 8 [ 3 6. 4 %] s u bjects), E C P  ( 4 1 [ 3 1. 1 %] s u bjects), a n d 
sir oli m us ( 3 6 [ 2 7. 3 %] s u bjects). 
Efficac y  
T he pri mar y efficac y e n d p oi nt, O R R, is prese nte d i n  Ta ble 3 . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
At t he c ut off date, 6  m o nt hs after t he last s u bject first visit, t he O R R wit h bel u m os u dil w as 
7 3. 5 % ( 9 5 % CI: 6 5. 1 %, 8 0. 8 %): 7 2. 7 % ( 9 5 % CI: 6 0. 4 %, 8 3. 0 %) i n Ar m A a n d 7 4. 2 % ( 9 5 % CI: 
6 2. 0 %, 8 4. 2 %) i n Ar m  B.  Acr oss b ot h ar ms, 4 ( 3. 0 %) s u bjects a c hie ve d C R a n d 9 3 ( 7 0. 5 %) 
s u bjects ac hie v e d P R.  Res p o nse rates b et wee n t he 2 ar ms were n ot n oticea bl y d iffere nt. 
Ta ble 3 . 
Pri m ar y Effic ac y E n d p oi nt  Res ults fr o m St u d y K D 0 2 5 -2 1 3  
Res p o nse R ate  
Ar m A  
2 0 0 m g  Q D  
N  =  6 6  
Ar m B 
2 0 0 m g  BI D  
N  =  6 6  
O ver all  
N = 1 3 2  
O R R ( C R  or  P R)  - n ( %) 
4 8 ( 7 2. 7) 
4 9 ( 7 4. 2) 
9 7 ( 7 3. 5) 
C R  
3 ( 4. 5) 
1  ( 1. 5) 
4 ( 3. 0) 
P R  
4 5  ( 6 8. 2) 
4 8  ( 7 2. 7) 
9 3  ( 7 0. 5) 
E xact met h o d  
9 5 %  CI of O R R  
( 6 0. 4, 8 3. 0) 
( 6 2. 0, 8 4. 2) 
( 6 5. 1, 8 0. 8) 
BI D = t wice dail y; CI  =  c o nfi de nce i nter val;  C R  = c o m plete res p o nse;  mI T T =  m o difie d I nte nt -t o-Treat;  O R R  = O verall  
Res p o nse Rate; P R = partial res p o nse;  Q D = o nce dail y  
N ote: mI T T P o p ulati o n  
N ote: 2 -si de d, e xact CI was cal c ulate d usi n g t he Cl o p per-P ears o n met h o d.  
N ote: R es ults b ase d o n c ut off dat a date 1 9 Fe br uar y 2 0 2 0.  
 
Safet y  
T he me dia n d urati o n of treat me nt  i n eac h ar m was 6 . 7 m o nt hs.  O verall, 6. 1 % of  s u bjects 
recei v e d > 1 2 m o nt hs of bel u m os u dil treat me nt.  T he me dia n relati ve d ose i nte nsit y ( R DI) was 
9 9. 7 %.   O verall , 1 1 0 ( 8 3. 3 %) s u bjects ha d a n R DI > 9 5 %: 5 4 ( 8 1. 8 %) s u bj ects i n Ar m A a n d 5 6 
( 8 4. 8 %) s u bjects i n Ar m B. 
Safet y res ults are pres e nte d i n Ta ble 4 .  
I n t otal, 1 3 0 ( 9 8. 5 %) s u bjects e x perie nce d ≥ 1 T E A E : 6 5 ( 9 8. 5 %) s u bjects i n Ar m A a n d 
6 5  ( 9 8. 5 %) s u bjects i n Ar m B.  T hirt y -fi ve ( 2 6. 5 %) s u bjects e x perie nce d ≥ 1 T E A E t hat le d t o 
d ose i nterr u pti o n: 1 9 ( 2 8. 8 %) s u bjects i n Ar m A a n d 1 6  ( 2 4. 2 %) s u bjects i n Ar m B.  T he m ost 
fre q ue nt T E A E t hat le d t o d ose i nterr u pti o n b y P T was p ne u m o nia ( 7 [ 5. 3 %] s u bjects): 
4  ( 6. 1 %) s u bjects i n Ar m A an d 3 ( 4. 5 %) s u bjects i n Ar m B.  Fi ve ( 3. 8 %) s u bjects e x perie nce d 
≥ 1 T E A E t hat le d t o d ose re d ucti o n: 2 ( 3. 0 %) s u bjects i n Ar m  A a n d 3 ( 4. 5 %) s u bjects i n 
Ar m  B.  
Fi ve s u bjects e x perie n ce d a S A E  t hat le d t o treat me nt disc o nti n uati o n: 4 s u bjects i n Ar m A 
(cell ulitis; as pirati o n; se ptic s h oc k; m ulti ple or ga n d ysf u ncti o n s y n dr o m e) a n d 1 s u bject i n 
Ar m  B (s e psis a n d micr oa n gi o p at hic he m ol ytic a n e mia).  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Fi ve s u bjects die d wit hi n 2 8 da ys of st u d y tr eat me nt.  F o ur s u bjects die d i n Ar m A d ue t o 
he m ot h ora x; as pirati o n a n d res pirat or y fail ure; se ptic s h oc k, m ulti ple or ga n d ysf u ncti o n 
s y n dr o me; a n d rec urre nt ac ute m yel oi d le u ke mia.  O ne s u bject die d i n Ar m B d ue t o car diac 
arrest.  T h e A E  of m ulti ple or ga n d ysf u ncti o n s y n dr o me was c o nsi d ere d  relate d t o bel u m os u dil.  
All ot her A E s t hat le d t o deat h were n ot c o nsi dere d relate d t o bel u m os u dil. 
Ta ble 4 . 
S afet y Res ults fr o m St u d y K D 0 2 5 -2 1 3  
S afet y O utc o mes  
Ar m A  
2 0 0 m g Q D  
N = 6 6  
n ( %)  
Ar m B  
2 0 0 m g BI D  
N = 6 6  
n ( %)  
O ver all  
N = 1 3 2  
n ( %)  
S u bj ects wit h  at least 1 T E A E  
6 5 ( 9 8. 5)  
6 5 ( 9 8. 5)  
1 3 0 ( 9 8. 5)  
S u bj ects wit h T E A Es b y ma xi m u m se verit y  
Gra de 1: Mil d  
5 ( 7. 6)  
4 ( 6. 1)  
9 ( 6. 8)  
Gra de 2: M o derate  
2 5 ( 3 7. 9)  
3 1 ( 4 7. 0)  
5 6 ( 4 2. 4)  
Gra de 3:  S e vere 
2 9  ( 4 3. 9) 
2 6  ( 3 9. 4) 
5 5  ( 4 1. 7) 
Gra de 4: L ife-t hreate ni n g 
2 ( 3. 0) 
3  ( 4. 5) 
5  ( 3. 8) 
Gra de 5: F atal 
4 ( 6. 1) 
1  ( 1. 5) 
5  ( 3. 8) 
T E A Es  b y  P T occ urri n g i n >  2 0 %  s u bjects o verall 
Fati g ue  
2 6  ( 3 9. 4) 
1 6 ( 2 4. 2) 
4 2 ( 3 1. 8) 
Diarr hea  
2 0  ( 3 0. 3) 
1 8  ( 2 7. 3) 
3 8  ( 2 8. 8) 
Na usea  
1 7 ( 2 5. 8) 
1 7  ( 2 5. 8) 
3 4  ( 2 5. 8) 
C o u g h  
1 9 ( 2 8. 8) 
1 3  ( 1 9. 7) 
3 2  ( 2 4. 2) 
D ys p nea  
2 0 ( 3 0. 3) 
1 1  ( 1 6. 7) 
3 1  ( 2 3. 5) 
U p per  res pirat or y tract i nfecti o n 
1 4  ( 2 1. 2) 
1 6  ( 2 4. 2) 
3 0  ( 2 2. 7) 
E de ma  peri p heral  
1 7  ( 2 5. 8) 
1 1  ( 1 6. 7) 
2 8  ( 2 1. 2) 
 
 
 
 
S u bj ects wit h at least 1  st u d y dr u g-relate d T E A E  
4 7  ( 7 1. 2) 
3 6  ( 5 4. 5) 
8 3  ( 6 2. 9) 
St u d y dr u g -relate d T E A Es b y P T occ urri n g i n >  1 0 % of  s u bjects o verall  
Fati g ue  
1 4  ( 2 1. 2) 
1 1 ( 1 6. 7) 
2 5 ( 1 8. 9) 
Na usea  
8  ( 1 2. 1) 
7  ( 1 0. 6) 
1 5  ( 1 1. 4) 
 
 
 
 
S u bj ects wit h at least 1  Gra de  3  T E A E  
3 5 ( 5 3. 0) 
3 0  ( 4 5. 5) 
6 5  ( 4 9. 2) 
Gra de  3  T E A Es b y  P T occ urri n g  i n  5 % of s u bjects o verall  
P ne u m o nia  
5  ( 7. 6) 
5 ( 7. 6) 
1 0  ( 7. 6) 
H y perte nsi o n  
3  ( 4. 5) 
4 ( 6. 1) 
7 ( 5. 3) 
S u bj ects wit h at least 1  st u d y dr u g -relate d Gra de  3  T E A E  
1 1  ( 1 6. 7) 
9  ( 1 3. 6) 
2 0  ( 1 5. 2) 
St u d y  dr u g -relate d Gra de 3  T E A Es  b y P T  occ urri n g i n  >  1 % of  s u bjects o verall 
Fati g ue  
0  ( 0) 
2  ( 3. 0) 
2  ( 1. 5) 
G G T  i ncrease d 
2 ( 3. 0) 
0  ( 0) 
2  ( 1. 5) 
Hea dac he  
0  ( 0) 
2  ( 3. 0) 
2  ( 1. 5) 
H y perte nsi o n  
0  ( 0) 
2 ( 3. 0) 
2 ( 1. 5) 
Na usea  
1  ( 1. 5) 
1 ( 1. 5) 
2 ( 1. 5) 
 
 
 
 
S u bj ects  wit h at least 1 S A E  
2 7  ( 4 0. 9) 
1 8  ( 2 7. 3) 
4 5  ( 3 4. 1) 
S A E s b y  P T occ urri n g i n >  2 % s u bjects o verall  
P ne u m o nia  
6  ( 9. 1) 
4 ( 6. 1) 
1 0  ( 7. 6) 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 2 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S afet y O utc o mes  
Ar m A  
2 0 0 m g Q D  
N = 6 6  
n ( %)  
Ar m B  
2 0 0 m g BI D  
N = 6 6  
n ( %)  
O ver all  
N = 1 3 2  
n ( %)  
P yre xia  
4  ( 6. 1) 
0 ( 0) 
4 ( 3. 0) 
D ys p nea  
1  ( 1. 5) 
2 ( 3. 0) 
3 ( 2. 3) 
L u n g i nfecti o n  
1  ( 1. 5) 
2 ( 3. 0) 
3 ( 2. 3) 
Se psis  
2  ( 3. 0) 
1  ( 1. 5) 
3  ( 2. 3) 
S u bj ects wit h at least 1  st u d y dr u g -relate d seri o us S A E  
6  ( 9. 1) 
1  ( 1. 5) 
7  ( 5. 3) 
 
 
 
 
S u bj ects wit h T E A E lea di n g t o  d ose disc o nti n uati o n  
1 4  ( 2 1. 2) 
9  ( 1 3. 6) 
2 3  ( 1 7. 4) 
S u bj ects wit h st u d y  dr u g -relate d T E A E lea di n g t o  d ose  
disc o nti n uati o n  
 
8  ( 1 2. 1) 
 
5  ( 7. 6) 
 
1 3  ( 9. 8) 
S u bj ects wit h T E A E lea di n g t o deat h  
4  ( 6. 1) 
1 ( 1. 5) 
5 ( 3. 8) 
BI D  = t wice dail y;  c G V H D = graft vers us  h ost  disease;  G G T  =  ga m ma  gl uta m yl tra nsferase; Me d D R A  = Me dical  Dicti o nar y  
f or Re g ulat or y  Acti vities; P T =  preferre d  ter m; Q D = o nce dail y;  S A E = seri o us (treat me nt -e mer ge nt) a d verse e ve nt; T E A E = 
treat me nt-e mer ge nt a d verse  e ve nt. 
N ote s: 
1. Safet y P o p ulati o n  
2. Me d D R A versi o n 2 0. 0.  
3. Defi nitel y relate d, pr o ba bl y relate d, a n d p ossi bl y relate d were all c o nsi dere d as relate d t o bel u m os u dil.  
4. A  s u bject wit h m ulti ple e ve nts wit hi n a cate g or y was c o u nte d o nl y o nce i n t h at cate g or y.  
5. A s u bject wit h m ulti ple c o n diti o ns wit hi n a P T was c o u nte d o nl y o nce f or t h at P T.  
6. T he res ults prese nte d are base d o n t h e data c ut -off date of 1 9 Fe br uar y 2 0 2 0.  
 
C o ncl usi o ns  
Bel u m os u dil at 2 0 0 m g Q D a n d 2 0 0 m g BI D de m o nstrate d cli nicall y m ea ni n gf ul res p o nses i n a 
p o p ulati o n of s u bjects wit h a d va nce d, h ea vil y pre -treate d c G V H D.  T he O R R f or t he mI T T 
P o p ulati o n was 7 3. 5 % ( 9 5 % CI: 6 5. 1, 8 0. 8): 7 2. 7 % ( 9 5 % CI: 6 0. 4, 8 3. 0) i n Ar m A ( Q D) a n d 
7 4. 2 % ( 9 5 % CI: 6 2. 0, 8 4. 2) i n Ar m B ( BI D).  T he p oi nt esti mates a n d 9 5 % CIs all e x cee d e d 
8 0. 8 %.  Res p o nses were d ura ble.  T h ese fi n di n gs were s u p p orte d b y s u b gr o u p a nal yses, a n d b y 
sec o n dar y a n d e x pl orat or y e n d p oi nts.  W hile t he O R R was si milar wit h b ot h d ose le vels, t here 
was a greater  res p o nse wit h BI D d osi n g i n or ga ns s uc h as t he s ki n a n d e ye, a n d a tre n d t o w ar ds a 
l o n ger D O R wit h BI D d osi n g.  T hes e res ults s u g gest a fa v ora bl e be nefit/ris k pr ofile f or b ot h 
d ose le vels.  
1. 5  St u d y R ati o n ale   
St u d y K D 0 2 5 -2 1 7 is a n e xte nsi o n st u d y of s u bjects e nr olle d a n d treate d i n St u d y K D 0 2 5 -2 0 8 
a n d St u d y K D 0 2 5 -2 1 3 . 
M ost s u bjects i n b ot h  St u d y K D 0 2 5 -2 0 8 a n d St u d y K D 0 2 5 -2 1 3  were tr eate d wit h b el u m os u dil at 
2 0 0 m g Q D or 2 0 0 m g BI D a n d ha d si milar i ncl usi o n/e x cl usi o n criteria.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
St u d y K D 0 2 5 -2 1 7 will b e  a n e xte nsi o n st u d y t o assess t he l o n g -t er m safet y a n d efficac y of t hese 
s u bjects treate d wit h bel u m os u dil, t he b ul k of w h o m were tr eate d wit h 2 0 0 m g Q D or 2 0 0 m g 
BI D, b ut als o s o me treate d wit h 4 0 0 m g Q D.   
1. 6  
S u m m ar y of K n o w n a n d P ote nti al Ris ks a n d Be nefits t o H u m a n S u bjects   
All p ossi ble si de effects r elate d t o bel u m os u dil  are n ot k n o w n ; the B el u m os u dil  I B c o ntai ns data 
o n ris ks ass ociate d wit h t his st u d y dr u g.   
S u bjects ma y recei ve a cli nical be nefit fr o m b el u m os u dil  w hile  s o me s u bjects ma y pr o gress.   
T his st u d y is i nte n de d t o assess t he l o n g -ter m cli ni cal be nefits a n d ris ks of bel u m os u dil f or t he 
treat me nt of c G V H D.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
2  S T U D Y O B J E C TI V E S   
T he o bjecti ve of t his st u d y is t o e val uat e l o n g -ter m safet y a n d effi cac y of bel u m os u dil i n s u bjects 
wit h c G V H D w h o h a ve pre vi o usl y b ee n treate d w it h bel u m os u dil i n St u d y K D 0 2 5-2 0 8 or 
St u d y  K D 0 2 5 -2 1 3.  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
3  I N V E S TI G A TI O N A L P L A N  
3. 1  St u d y Desi g n   
T his wil l be a P hase 2, o pe n -la bel, e xte n de d  treat me nt a n d f oll o w-u p st u d y i n s u bjects wit h 
c G V H D w h o ha ve b ee n pre vi o usl y tr eate d wit h b el u m os u dil i n St u d y K D 0 2 5 -2 0 8 (see 
Secti o n  1. 4. 1 ) or i n St u d y K D 0 2 5-2 1 3 (see Secti o n  1. 4. 2 ). 
S u bjects will n ot be scree ne d.  
S u bjects w h o ha ve si g n e d t he I C F will be e nr olle d i n St u d y K D 0 2 5-2 1 7 if t he y h a ve met a n y of 
t he f oll o wi n g c o n diti o ns: 
•  Acti vel y recei vi n g b el u m os u dil  i n St u d y K D 0 2 5-2 0 8  or i n St u d y K D 0 2 5 -2 1 3  (e x cl u di n g 
a d ults i n t he C o m pa ni o n St u d y a n d e x cl u di n g a d olesce nts e nr olle d u n d er K D 0 2 5 -2 1 3 
A me n d me nt 2 [0 1J u ne 2 0 2 0 ]) 
•  Is i n l o n g-ter m f oll o w-u p  ( L F T U) o n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3.  
L o n g -t er m f oll o w-u p  will be defi ne d as t h e peri o d after e n di n g tr eat me nt wit h 
bel u m os u dil a n d u ntil a n F F S e v e nt occ urs.  
•  A d ult e nr olle d i n t he C o m pa ni o n St u d y as s pecifi e d i n St u d y K D 0 2 5 -2 1 3 A me n d me nt 2 
( 0 1 J u ne 2 0 2 0) a n d recei ve d at least 6 m o nt hs of treat me nt or is i n L T F U  
After si g ni n g t he I C F, at Baseli ne , s u bjects will u n der g o efficac y ass ess me nts b y 
Cli nicia n -re p orte d Gl o b al c G V H D Acti vit y Assess me nt, res p o nse assess m e nt, p ul m o nar y 
f u ncti o n tests ( P F Ts), Lee S y m pt o m Scale ( L S S) sc ore, a n d d o c u me ntati o n of c ortic oster oi d 
d osa ge a n d/ or ot her t hera pies f or c G V H D.  
S u bjects will u n der g o s afet y assess me nts i ncl u di n g s y m pt o m -direct e d  P E, vital si g ns, wei g ht,  
hei g ht,  K P S, he mat ol o g y a n d cli nical c he mistr y la b orat or y testi n g,  pre g n a n c y t esti n g, 1 2lea d 
E C G, d oc u me nti n g c o nc o mita nt me dicati o ns, a n d m o nit ori n g f or A Es.  S u bjects will c o nti n ue o n 
t heir sa me d osi n g re gi me n t he y recei ve d i n St u d y K D 0 2 5-2 0 8 or St u d y  K D 0 2 5 -2 1 3 : bel u m os u dil 
2 0 0 m g Q D, 2 0 0 m g BI D, or 4 0 0 m g Q D.  If t he I n vesti gat or re d uce d t he s u bject’s d ose  of 
bel u m os u dil i n eit her St u d y  K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3, t he s u bject will  c o nti n ue t o 
recei v e t hat sa me re d uce d d ose treat me nt wit h bel u m os u dil t hr o u g h o ut St u d y K D 0 2 5-2 1 7  or 
u ntil t he A E  t hat le d t o t he te m p orar y d os e re d u cti o n has res ol ve d, i n w hic h case t he d os e 
treat me nt ca n res u me at t he ori gi n al d ose at t he discreti o n of the I n v esti gat or .  S u bjects will be 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
gi ve n a st u d y dr u g diar y t o rec or d dail y d osi n g.  S u bjects ma y b e a d mi nistere d t he first d ose 
eit her i n t he cli nic or self -a d mi nistere d at h o me.  
At 3 m o nt hs after Baseli ne  a n d e v er y 3 m o nt hs t hereafter ( ± 1 4 da ys), s u bj ec ts will re p ort t o t he 
cli nic f or t he sa me efficac y a n d safet y assess me nts a n d dis pe nsi n g of bel u m os u dil  at Baseli ne .  
( Hei g ht is o nl y re q uire d at Bas eli ne .)  T h e st u d y dr u g diaries f or t he past 3 m o nt hs will be 
c ollecte d, a n d n e w st u d y dr u g diaries dis pe ns e d.  A n y re mai ni n g bel u m os u dil will be c ollecte d.  
S u bjects ma y recei ve bel u m os u dil o n St u d y K D 0 2 5 -2 1 7 f or u p t o a n a d diti o nal 2 years , at t he 
discreti o n of t he I n v esti gat or (a n d wit h g ui da nce fr o m t he me dical m o nit or),  be y o n d w hat t he y 
ha d recei ve d i n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3,  c G V H D pr o gressi o n , or u nacce pta ble 
t o xicit y. 
Efficac y a n d s afet y e n d p oi nts are descri be d i n Secti o n  6. 3  a n d Secti o n  6. 4 , res pecti vel y. 
S u bjects will ret ur n t o t he cli nic f or a  2 8 -da y  F oll o w -u p Visit at 2 8 da ys ( ± 7 da ys) after t he last 
d ose of st u d y dr u g.  S u bjects will ha ve L F T U  a p pr o xi matel y e ver y 3 m o nt hs u ntil a n  F F S e ve nt 
occ urs .  After t h e 2 8-da y F oll o w -u p Visit has bee n c o m plete d, s u bjects will be c o ntact e d 
a p pr o xi matel y e ver y 3 m o nt hs b y tele p h o ne, e -mail, or p ostal mail t o c o nfir m s ur vi val stat us, 
a n y i nitiati o n of ne w s yst e mic c G V H D t hera pies, a n d rela ps e of u n derl yi n g disease.  
Alter nati vel y, t his i nf or m ati o n ma y b e o btai ne d fr o m t he s u bject ’s me dical rec or ds.  T he 
Sc he d ule of Assess me nts is prese nte d i n  A p pe n di x  A: Sc he d ule of Assess me nts . 
3. 2  Esti m ate d St u d y D ur ati o n   
S u bjects ma y recei ve bel u m os u dil  f or 2 years at t he discreti o n of t he In vesti gat or a n d wit h 
g ui da n ce fr o m t he me dic al m o nit or.  
S u bjects will be treate d wit h bel u m os u dil u ntil c G V H D pr o gressi o n or u n acce pta ble t o xicit y.  
S u bjects will ret ur n t o t he cli nic f or a 2 8 -da y F oll o w -u p Visit ( ± 7 da ys) after t he last d ose of 
st u d y dr u g.  S u bjects will ha ve l o n g -ter m f oll o w-u p a p pr o xi matel y e ver y 3 m o nt hs u ntil a n F F S  
e ve nt occ urs .  After t he 2 8-da y F oll o w -u p Visit has bee n c o m plete d, s u bjects will be c o ntacte d 
a p pr o xi matel y e ver y 3 m o nt hs b y tele p h o ne, e -mail, or p ostal mail t o c o nfir m s ur vi val stat us,  
a n y i nitiati o n of ne w s yst e mic c G V H D t hera pies, a n d rela ps e of u n derl yi n g disease  (see 
Secti o n  3. 1 ).  Alter n ati vel y, t his i nf or mati o n ma y be o btai ne d fr o m t he s u bj ect’s me dical rec or ds. 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
4  S T U D Y P O P U L A TI O N   
4. 1  N u m ber of S u bjects   
A p pr o xi matel y 7 0 s u bj ects  ma y be e nr olle d . 
4. 2  St u d y Ce nters   
T his st u d y will be c o n d u cte d at a p pr o xi matel y 2 0  sites. 
4. 3  I ncl usi o n Criteri a  
1.  S u bjects m ust ha ve bee n treate d wit h bel u m os u dil f or at least 1 of t h e f oll o wi n g  criteria: 
a. Acti vel y recei vi n g b el u m os u dil o n St u d y K D 0 2 5 -2 0 8  or o n St u d y K D 0 2 5 -2 1 3  
(e x cl u di n g a d ults i n t he C o m pa ni o n St u d y a n d e x cl u di n g a d ol esce nts e nr olle d 
u n der K D 0 2 5 -2 1 3 A me n d me nt 2 [0 1  J u ne 2 0 2 0]) 
b.  Is i n L T F U  o n St u d y K D 0 2 5 -2 0 8  or o n K D 0 2 5 -2 1 3 .  L o n g-t er m F oll o w -u p will 
be defi ne d as t he peri o d after e n di n g tr eat me nt wit h bel u m os u d il a n d u ntil a n F F S 
e ve nt occ urs.  
c. A d ult e nr olle d i n t he C o m pa ni o n St u d y u n d er K D 0 2 5 -2 1 3 A me n d m e nt 2 
( 0 1 J u ne 2 0 2 0) w h o has recei ve d at least 6 m o nt hs of treat me nt of b el u m os u dil or 
is i n l o n g-ter m f oll o w-u p  
2.  Fe male s u bjects of c hil d beari n g p ote ntial ha v e a ne gati ve pre g n a nc y test at e nr oll me nt. 
Fe males of c hil d beari n g p ote ntial are defi ne d as s e x uall y m at ure fe males wit h o ut pri or 
h ysterect o m y or w h o h a v e ha d a n y e vi de nce of me nses i n t he past 1 2  m o nt hs.  H o we ver, 
fe males w h o h a ve bee n a me n orr heic f or 1 2 or more m o nt hs are still c o nsi dere d t o be of 
c hil d beari n g p ote ntial if t he a me n orr hea is p ossi bl y d ue t o pri or c he m ot hera p y, 
a nti-estr o ge ns, or o v aria n s u p pressi o n.  
3.  Se x uall y acti ve fe m ales of c hil d beari n g p ote ntial e nr olle d i n t he st u d y m ust a gree t o use 
2  f orms of acce pte d m et h o ds of c o ntrace pti o n d uri n g t he c o urse of t he st u d y a n d f or 
3  m o nt hs after t heir last d ose of st u d y dr u g. Effecti ve birt h c o ntr ol i ncl u des:  
a. I ntr a uteri ne d e vice pl us 1 barrier m et h o d 
b.  Sta ble d oses of h or m o nal c o ntrace pti o n f or at least 3 m o nt hs (e. g., oral, i njecta ble, 
i m pla nt, tra ns der mal) pl us 1  barrier m et h o d  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
c. 2  barrier m et h o ds.  Effecti ve barrier met h o ds are male or fe m ale c o n d o ms, 
dia p hra g ms, a n d s per mici des (crea ms or gels t hat c o ntai n a c h e mical t o kill 
s per m) or 
d.  A vasect o miz e d part ne r 
4.  F or male s u bjects w h o are se x uall y acti ve a n d w h o are part ners of fe mal es of c hil d beari n g 
p ote ntial: a gree me nt t o use 2  f or ms of c o ntr ace pti o n a n d t o n ot d o nate s per m d uri n g t he 
treat me nt peri o d a n d f or at least 3 m o nt hs after t h e last d ose of st u d y dr u g. 
5.  S u bject ( or t he s u bject ’s l e gall y a ut h orize d re prese ntati ve) is a ble t o pr o vi de writte n 
i nf or me d c o nse nt pri or t o t he perf or m a nce of a n y st u d y-s pecific pr oce d ures. 
6.  It is i n t he best i nterest of t he s u bject t o partici pate i n t he st u d y. 
4. 4  E xcl usi o n Criteri a   
1.  Fe male s u bject w h o is pre g n a nt or breastfee di n g  
2.  S u bject c o nsi dere d u nli k el y t o a d here t o treat me nt a n d/ or f oll o w pr ot oc ol i n t he o pi ni o n of 
t he In v esti gat or  
4. 5  Scree ni n g   
N o scree ni n g will be perf or me d i n t his st u d y.  S u bjects w h o meet t he i ncl usi o n /e xcl usi o n criteria 
will be i ncl u de d o nce t he I C F is si g ne d.  
4. 6  Wit h dr a w al Criteri a   
S u bjects will recei ve b el u m os u dil treat me nt u ntil cli nicall y si g nifica nt pr o gressi o n of c G V H D 
( defi ne d as pr o gressi o n re q uiri n g a d diti o n of ne w s yste mic t hera p y f or c G V H D), hist ol o gic 
rec urre nce of u n derl yi n g mali g na n c y, u nacce pta bl e t o xicit y, I n vesti gat or d ecisi o n, s u bject 
prefere nce/ wit h dra w al of c o nse nt, l oss t o f oll o w -u p, S p o ns or  decisi o n, or deat h ( w hic he ver 
occ urs first).  
S u bjects w h o e x perie nce c G V H D pr o gressi o n as d efi ne d b y NI H criteria b u t f or w h o m n o ne w 
s yste mic t hera p y is pla n n e d ma y c o nti n ue t o recei ve bel u m os u dil a n d be assesse d a gai n at t heir 
ne xt visit .  If pr o gressi o n per NI H criteri a is n ot c o nfir me d or n o ne w s yst e mic t hera p y is 
pla n ne d, s u bjects ma y c o nti n ue o n bel u m os u dil at t he In v esti gat or ’s discreti o n u ntil s u bjects 
f ulfill at least 1 criteri o n re q uiri n g disc o nti n uati o n of st u d y dr u g. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
Bel u m os u dil ma y b e t a pere d aft er a s ustai ne d res p o nse f or 6 m o nt hs a n d cessati o n of all ot her 
i m m u n os u p pressa nts f or at least 3 m o nt hs.  T he ta peri n g s c he d ule f or bel u m os u dil is descri be d 
i n D osa ge a n d A d mi nistrati o n  5. 2 . 
S u bjects ma y be wit h dra w n fr o m st u d y tr eat me nt at a n y ti me b y t h e I n vesti gat or or t he S p o ns or  
if it is c o nsi dere d detri me ntal f or t he s u bject t o c o nti n ue i n t he st u d y.  T h e reas o n f or wit h drawal 
will  be ca pt ure d i n t he e C R F.  
S u bjects ha ve t he ri g ht t o wit h dra w fr o m t he st u d y at a n y ti me a n d f or a n y reas o n wit h o ut 
prej u dice t o t heir f ut ure me dical care b y t he p h ysi cia n or at t he i nstit uti o n.  If t he s u bject wis hes 
t o v ol u ntaril y wit h dra w fr o m the st u d y, t he p h ysicia n will c o ns ult wit h t he s u bject re gar di n g 
pr oce d ures f or s afe wit h dra wal.  E v er y eff ort s h o ul d be ma de t o ha ve s uc h s u bjects atte n d 
pr ot oc ol visits i ncl u di n g t he 2 8 -da y F oll o w -u p V isit.  R eas o ns f or wit h dra wal of c o nse nt will be 
ca pt ure d i n t he e C R F.  S u bject data u p t o wit h dra wal of c o nse nt will be i n cl u de d i n t he a nal ysis 
of t he st u d y, a n d w h ere p er mitte d, p u blicl y a v aila ble data ca n be i ncl u de d after wit h dra wal of 
c o nse nt.  
4. 7  Re pl ace me nts   
N o s u bjects will be re pla ce d i n t his st u d y.  
4. 8  Tre at me nt Disc o nti n u ati o n   
Reas o ns f or disc o nti n uati o n of treat me nt wit h bel u m os u dil i ncl u de : 
•  Cli nicall y si g nifica nt c G V H D pr o gressi o n re q uiri n g a d diti o n of s yste mic t hera p y  
•  Pr o gressi o n of u n derl yi n g diseas e  as d efi ne d b y esta blis he d disease s pecific criteri a  
•  A n A E t hat re q uires per ma ne nt disc o nti n uati o n of st u d y dr u g  
•  I n v esti gat or decisi o n  
•  Vol u nta r y disc o nti n uati o n / wit h dra wal fr o m st u d y b y s u bject  (su bject ma y re mai n eli gi ble 
f or f oll o w-u p ) 
•  N o nc o m plia nce t o pr ot oc ol  
•  S u bject l ost t o f oll o w -u p  
•  Ter mi nati o n of t he st u d y b y S p o ns or  
•  S u bject deat h  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5  S T U D Y T R E A T M E N T   
5. 1  I n vesti g ati o n al Pr o d uct  
Bel u m os u dil ( 2-( 3-( 4-( 1 H-i n daz ol-5 -yl a mi n o) q ui naz oli n -2 -yl) p he n o x y) -N -is o pr o p yl aceta mi de-
met ha ne s ulf o nic aci d salt ), pre vi o usl y  k n o w n as  K D 0 2 5 , is a n orall y a v aila ble R O C K 2 selecti ve 
i n hi bit or.  B el u m os u dil  will be pr o vi de d as 2 0 0  m g ta blets.  
5. 2  D os a ge a n d A d mi nistr ati o n   
S u bjects will be treate d wit h t he sa me d osa ge of bel u m os u dil as t he y were assi g ne d i n 
St u d y  K D 0 2 5 -2 0 8 or  St u d y K D 0 2 5 -2 1 3:  
•  St u d y K D 0 2 5 -2 0 8:  bel u m os u dil 2 0 0 m g Q D, bel u m os u dil 2 0 0 m g BI D , or bel u m os u dil 
4 0 0 m g Q D  
•  St u d y K D 0 2 5 -2 1 3:  bel u m os u dil 2 0 0 m g Q D or bel u m os u dil 2 0 0 m g  BI D  
 
Bel u m os u dil will be ta pere d aft er a s ustai ne d res p o nse f or 6 m o nt hs a n d cessati o n of all ot her 
i m m u n os u p pressa nts f or at least 3 m o nt hs.  Ta peri n g is als o e x pecte d if s u bjects wit h dra w f or 
reas o ns ot her t h a n c G V H D pr o gressi o n or a d verse e ve nts.  T he ta peri n g sc h e d ule f or 
bel u m os u dil is as f oll o ws:  
 
•  2 0 0 m g Q D → 2 0 0 m g Q O D f or 1 m o nt h → Disc o nti n ue  
•  2 0 0 m g BI D  → 2 0 0 m g Q D  f or 1 m o nt h →2 0 0 m g Q O D f or 1 m o nt h → Disc o nti n ue  
•  4 0 0 m g Q D  → 2 0 0 m g Q D  f or 1 m o nt h →2 0 0 m g Q O D f or 1 m o nt h → Disc o nti n ue  
 
5. 3  Tre at me nt Assi g n me nt   
S u bjects will c o nti n ue t o recei v e t he sa me d os a ge of bel u m os u dil ( 2 0 0 m g Q D, 2 0 0 m g BI D, or 
4 0 0 m g Q D) as t he y w ere assi g n e d i n St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3.   If t he 
I n v esti gat or re d u ce d t he d ose of bel u m os u dil i n eit her St u d y K D 0 2 5-2 0 8 or St u d y K D 0 2 5 -2 1 3, 
t he s u bject will  c o nti n ue t o recei ve t h at sa me re d u ce d d ose tr eat me nt wit h bel u m os u dil t hr o u g h 
St u d y K D 0 2 5 -2 1 7  or u ntil t he A E  t hat le d t o t he te m p orar y d os e red u cti o n has res ol ve d , i n w hic h 
t he d ose treat me nt ca n res u me at t he ori gi nal d ose at t he discreti o n of t he I n vesti gat or. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5. 4  Bli n di n g   
T his will be a n o pe n -la bel st u d y.  N o s u bjects will be bli n de d. 
5. 5  Tre at me nt C o m pli a nce   
S u bjects will be gi ve n a st u d y dr u g diar y t o rec or d t he details of eac h d ose of st u d y dr u g.  
5. 6  Misse d D oses   
S u bjects s h o ul d ma ke e v er y eff ort t o ta ke t h e st u d y dr u g at t he sa me sc h e d ule d ti me dail y wit h 
t heir m or ni n g/e v e ni n g meal or wit hi n 5 mi n utes of c o m pleti n g t he m eal.  I n t he e ve nt t hat t he 
s u bject misses t he pla n ne d d ose of st u d y dr u g, t he pr ot oc ol  bel o w  s h o ul d be f oll o we d: 
F or s u bjects r ecei vi n g st u d y dr u g o n a Q D d osi n g sc he d ule:  
•  If less t ha n 1 2 h o urs of ti me ha ve el a pse d after t he sc he d ule d d ose, t he dr u g s h o ul d be 
ta ke n. T he s u bject s h o ul d t he n res u me t he re g ular pla n ne d dail y d osi n g s c h e d ule t he 
f oll o wi n g da y. 
•  If m ore t ha n 1 2 h o urs of ti me ha ve ela pse d after t he sc he d ule d d os e, t he dr u g s h o ul d be 
s ki p pe d f or t hat da y. T he s u bject s h o ul d t he n res u me t he re g ular pla n ne d d osi n g sc he d ul e 
t he f oll o wi n g da y. 
F or  s u bjects r ecei vi n g st u d y dr u g o n a BI D d osi n g sc h e d ule:  
•  If less t ha n 6 h o urs of ti me ha ve el a pse d after t he sc he d ule d d ose, t he dr u g s h o ul d be 
ta ke n. T he s u bject s h o ul d t he n res u me t he re g ular pla n ne d d osi n g s c he d ule. 
•  If m ore t ha n 6 h o urs of ti me ha ve el apse d after t he sc he d ule d d ose, t he d os e s h o ul d be 
s ki p pe d a n d t he s u bject s h o ul d res u me d osi n g wit h t he ne xt t he re g ular pla n ne d d ose.    
If t he s u bject s ki ps m ore t ha n 7 c o nsec uti ve d a ys of dr u g, t he s u bject s h o ul d be disc o nti n ue d 
fr o m t he st u d y u nless a p pr o ve d b y t he me dical m o nit or a n d I n vesti gat or. 
I n t he e ve nt of v o miti n g, t he s u bject s h o ul d re p ort t he A E a n d s h o ul d n ot ta ke a d diti o nal d oses of 
st u d y dr u g t o c o m pe ns ate. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 3 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5. 7  Pr o d uct Acc o u nt a bilit y   
I n acc or da n ce wit h re g ul at or y re q uir e me nts, st u d y sites m ust d oc u me nt t he a m o u nt of 
bel u m os u dil  recei ve d fr o m a n d ret ur ne d t o t he S p o ns or , t he a m o u nts of bel u m os u dil dis pe nse d t o 
st u d y s u bjects, a n d t he a m o u nt ret ur ne d b y st u d y s u bjects.  Pr o d uct acc o u nta bilit y rec or ds m ust 
be mai ntai ne d t hr o u g h o ut t he c o urse of t he st u d y .  
5. 8  C o nc o mit a nt Me dic ati o ns a n d Pr oce d ures   
All c o nc o mita nt me dicati o ns i ncl u di n g dietar y/ h er bal/ o ver t he c o u nter s u p ple me nts ta ke n d uri n g 
t he st u d y a n d rele v a nt pr oce d ures will be rec or de d.   I nitiati o n of ne w s yst e mic c G V H D t hera p y 
will be c o nsi dere d a ne w li ne of treat me nt a n d a bel u m os u dil  treat me nt fail ure. 
5. 8. 1  
C ortic ost er oi ds   
C ortic oster oi d d ose data will be c ollecte d t hr o u g h o ut t he st u d y.  C ortic oster oi ds ma y b e ta pere d 
at t he discreti o n of t he I n vesti gat or. 
Tra nsie nt i ncreas es i n c ortic oster oi d d os i n g ( n ot e x cee di n g 1 m g/ k g/ da y pre d nis o ne e q ui vale nt , 
see A p p e n di x  K : Pre d nis o ne D ose E q ui vale nts ) are per mitte d f or t he treat m e nt of c G V H D flare, 
b ut t he d ose m ust be re d uce d wit hi n 6  wee ks.  If t he d ose re m ai ns ele vate d f or m ore t ha n 6  
wee ks,  t his will be c o nsi dere d a b el u m os u dil treat me nt fail ure. 
5. 8. 2  
S yste mic c G V H D T her a pies   
S u bjects ma y be recei vi n g t he sta n d ar d of care s yste mic c G V H D t h era pies s uc h as C NIs  
(tacr oli m us, c ycl os p ori ne), sir oli m us, m yc o p he n ol ate m ofetil , met h otre x ate, rit ux i ma b, or E CP.  
C ha n ges i n d os es of dr u gs t o mai ntai n t hera pe utic le vels are n ot c o nsi dere d as a c ha n ge i n 
d ose/sc he d ule.  
5. 8. 3  
T o pic al / Or g a n S pecific T her a pies f or c G V H D   
Use of t o pical/ or ga n s p ecific t hera pies f or c G V H D is per mitte d  b ut m ust be d oc u me nte d.  
5. 8. 4  
C Y P  3 A 4 I n d ucers   
Use of str o n g C Y P 3 A 4 i n d ucers  decreases bel u m os u dil e x p os ure  (A p pe n di x  H : Dr u gs t hat 
I n d u ce C Y P 3 A 4). 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5. 8. 5  
Dr u gs Pr ol o n gi n g t he Q Tc I nter v al   
Dr u gs t hat pr ol o n g Q T/ Q Tc s h o ul d be use d wit h ca uti o n (A p pe n di x  J: Dr u gs T h at Pr ol o n g Q Tc ). 
5. 8. 6  
Pr o hi bite d  C o nc o mit a nt Me dic ati o ns   
Treat me nt wit h i n vesti gati o nal s yste mic i m m u n os u p pressa nt dr u gs f or c G V H D (i ncl u di n g 
r u x oliti ni b) is pr o hi bite d. 
5. 9  Tre at me nt o f O ver d ose   
D oses of bel u m os u dil  c o nsi dere d t o re prese nt a n o ver d ose ha v e n ot bee n d efi ne d.  I n cli nical 
st u dies of bel u m os u dil  i n healt h y v ol u nteers, re peat d osi n g of 5 0 0 m g BI D f or 2 8 da ys was 
ge n erall y w el l-t olerate d.  T here are n o k n o w n a nti d otes t o bel u m os u dil ; n o s pecific treat me nt is 
rec o m me n de d i n t he e ve nt of a s us pecte d o ver d ose.  T he tr eati n g I n vesti gat or s h o ul d e m pl o y 
cli nical j u d g me nt i n ma n a gi n g s u bjects wit h s us pecte d o ver d ose.   O ver d ose s h o ul d be re p orte d 
as a n A E (Secti o n  7. 2 ) re gar dless of w h et her  t here are a n y ot h er ass o ciate d A E s.  
5. 1 0  D ose M o dific ati o n G ui deli nes   
A n y cli nicall y si g nifica nt t o xicit y will necessitate c o nsi derati o n of eit her a pa use or cessati o n of 
t hera p y.  G ui deli nes f or ma na ge me nt of tr eat me nt -e mer ge nt t o xicities i n s u bjects recei vi n g 
bel u m os u dil  are o utli ne d i n  Ta ble 5 .  W he n d ose re d ucti o n is necessar y, t he d ose s h o ul d be 
decrease d as s h o w n i n Ta ble 6 . 
Ta ble 5 . 
G ui deli nes f or t he M a n a ge me nt of T E A Es wit h Bel u m os u dil Tre at me nt  
T o xicit y  
Rec o m me n de d Acti o n  
Gra d e 4 or ga n t o xicities 
c o nsi dere d at least 
p ossi bl y relate d t o 
bel u m os u dil  
•  
Disc o nti n ue bel u m os u dil  
Gra d e ≥ 3 L F Ts ( A S T, 
A L T or t otal bilir u bi n) 
re gar dless of attri b uti o n 
t o bel u m os u dil  
•  
H ol d bel u m os u dil  d osi n g u ntil res ol uti o n t o Gra de 1 or bel o w le vels  
•  
C o nsi der res u mi n g bel u m o s u dil.  If res u mi n g, t he n res u me at 1  d ose 
decre me nt  
•  
If t o xicit y rec urs, disc o nti n ue bel u m os u dil  
Ot her Gra d e ≥3 
cli nicall y si g nifica nt 
t o xicities c o nsi dere d at 
least p ossi bl y relate d t o 
bel u m os u dil   
•  
H ol d bel u m os u dil  d osi n g u ntil t o xicit y has res ol ve d t o Gra de 1 or bel o w 
t he n c o nsi der res u mi n g bel u m os u dil . If res u mi n g, t he n res u me at 1  d ose 
decre me nt  
•  
If t o xicit y rec urs, h ol d d ose as a b o ve t he n c o nsi der res u mi n g bel u m os u dil  
at o ne d ose decre me nt  
A L T = ala ni n e a mi n otra nsferase; A S T = as partate a mi n otra nsfer ase; e C R F = electr o nic case re p ort f or m; L F T = li ver f u ncti o n 
test; T E A E = treat me nt-e mer ge nt a d verse e ve nt  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
D ose i nterr u pti o n f or u p t o 1 4 da ys f or t o xicit y m a na ge me nt is per mitte d.  S u bjects re q uiri n g 
pa uses of m ore t h a n 1 4  d a ys will be disc o nti n ue d fr o m t he st u d y  u nless a p pr o ve d b y t he m e dical 
m o nit or. 
Ta ble 6 . 
Bel u m os u dil D ose Decre me nts  
Bel u m os u dil D ose  
D ose Re d ucti o n  
4 0 0 m g Q D  
2 0 0 m g Q D  
2 0 0  m g BI D  
2 0 0  m g Q D  
2 0 0  m g Q D  
2 0 0  m g Q O D  
BI D = t wice dail y; Q D =  o nce dail y; Q O D = o nce e ver y ot h er da y  
 
If t he re d u ce d d os e of bel u m os u dil is t olerate d f or 1 m o nt h , t he d ose ma y b e escal ate d t o t he 
pre vi o us d ose.  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
6  S T U D Y A S S E S S M E N T S A N D P R O C E D U R E S   
6. 1  Sc he d ule of Assess me nts   
T he efficac y a n d safet y assess me nts f or t his st u d y are prese nte d i n A p pe n di x  A: Sc he d ule of 
Assess me nts . 
6. 2  St u d y Visits   
6. 2. 1  
Scree ni n g   
T his st u d y will  ha ve n o f or mal scree ni n g.  
S u bjects w h o meet all i ncl usi o n/e x cl usi o n criteria a n d si g n t he I C F will be e nr olle d i n t he st u d y.  
6. 2. 2  
B aseli ne  Visit   
S u bjects will be e val uate d t o deter m i ne if t he y meet all i ncl usi o n/e xcl usi o n criteria.  T h os e 
si g ni n g t he I C F will be e nr olle d i n t he st u d y.  
N ote:  If t he s u bject w as i n L T F U  i n St u d y  K D 0 2 5 -2 0 8 or i n St u d y  K D 0 2 5 -2 1 3, t he  s u bject will 
o nl y ha v e L T F U assess m e nts perf or m e d o nce a p pr o xi matel y e v er y 3 m o nt hs  (Secti o n  6. 2. 5 ).   
Bel u m os u dil  will be a d mi nistere d as f oll o ws:  
•  S u bject recei v es sa me d os e of bel u m os u dil as assi g ne d i n St u d y K D 0 2 5 -2 0 8 or i n 
St u d y  K D 0 2 5 -2 1 3, as a p pr o priate.  T h e first d ose ma y b e ta ke n at h o me or i n t he cli nic.  
•  Dis pe nse a st u d y dr u g di ar y t o t he s u bject  
T he f oll o wi n g d ata will n ee d t o be ca pt ure d fr o m St u d y K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3:  
•  T he d osi n g gr o u p t o w hic h t he s u bject was assi g n e d or ra n d o mize d  
•  Cli nicia n -re p orte d Gl o b al c G V H D Acti vit y A ssess me nt fr o m Da y 1 
•  A n y o n g oi n g  A E s 
T he f oll o wi n g efficac y assess me nts will be perf or me d : 
•  Cli nicia n -re p orte d Gl o b al c G V H D Acti vit y A ssess me nt 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  Res p o nse assess me nt .  ( N ote: all res p o nses will b e  assesse d wit h r es pect t o C ycle 1 Da y 1 
of St u d y  K D 0 2 5 -2 0 8 or St u d y K D 0 2 5 -2 1 3 .) 
•  P F T  (f or s u bj ects wit h l u n g c G V H D or w he n l u n g c G V H D is s us pecte d) 
•  L S S  
•  Use of c ortic oster oi d d os a ge  
•  Use of ot her c G V H D t hera pies  
T he f oll o wi n g s afet y assess me nts will be perf or m e d:  
•  S y m pt o m -dir ecte d P E  
•  Vital si g ns  
•  Wei g ht a n d hei g ht  
•  K P S  
•  He mat ol o g y l a b testi n g  
•  Cli nical c he mistr y la b testi n g  
•  1 2 -lea d E C G 
•  Uri ne pre g n a nc y test ( a n y p ositi ve res ults will be c o nfir me d wit h se r u m testi n g) 
•  Use of c o n c o mita nt me dicati o ns  
•  A Es  
6. 2. 3  
M o nt h 3 Visit  a n d E ver y 3 M o nt h Visits T here after  ( ± 1 4 d a ys)  
T hree m o nt hs ( ± 1 4 da ys) after Baseli ne , s u bjects will ha ve t he f ollo wi n g 
pr oce d ures/assess me nts:  
•  C ollecti o n of a n y re mai ni n g bel u m os u dil fr o m s u bject  
•  Dis pe nsi n g bel u m os u dil me dicati o n at t he sa me d ose.  D oses  ma y be t a ke n at h o me or i n 
t he cli nic. 
•  C ollecti o n of st u d y dr u g diar y  
•  Dis pe nsi n g ne w st u d y dr u g diar y  
•  Cli nicia n -rep orte d Gl o b al c G V H D Acti vit y assess me nt  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  Res p o nse assess me nt  
•  P F T *  
•  L S S  
•  Use of c ortic oster oi d d os a ge  
•  Use of ot her c G V H D t hera pies  
•  S y m pt o m -dir ecte d P E  
•  Vital si g ns  
•  Wei g ht  
•  K P S  
•  He mat ol o g y l a b testi n g  
•  Cli nical c he mistr y la b testi n g  
•  1 2 -lea d E C G 
•  Uri ne pre g n a nc y test  (a n y p ositi ve res ults will be c o nfir me d wit h ser u m testi n g) 
•  Use of c o n c o mita nt me dicati o ns  
•  A Es  
* W he n perf or mi n g P F T , t he sa me e q ui p me nt a n d tester s h o ul d be use d d uri n g t he c o urse of t he 
st u d y w he n p ossi ble.  T h e P F Ts s h o ul d be c o n d u cte d i n acc or da nce wi t h st u d y g ui deli nes a n d t h e 
A merica n T h oracic S ociet y/ E ur o pea n Res pirat or y S ociet y sta n dar dizati o n of l u n g f u ncti o n 
testi n g. 
6. 2. 4  
2 8 D a y F oll o w -U p Visit   
T h is 2 8 -da y F oll o w -u p V isit (±  7 da ys) will be 2 8 da ys after t h e last d ose of bel u m os u dil.  
S u bjects will ha ve t he f oll o wi n g assess me nts a n d pr oce d ures:  
•  C ollecti o n of a n y re mai ni n g bel u m os u dil fr o m s u bject  
•  C ollecti o n of st u d y dr u g diar y  
•  Use of c ortic oster oi d d os a ge  
•  Use of ot her c G V H D t h era pies  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  S y m pt o m -dir ecte d P E  
•  Vital si g ns  
•  Wei g ht  
•  K P S  
•  He mat ol o g y l a b testi n g  
•  Cli nical c he mistr y la b testi n g  
•  1 2 -lea d E C G 
•  Uri ne pre g n a nc y test ( a n y p ositi ve res ults will be c o nfir me d wit h ser u m testi n g)  
•  Use of c o n c o mita nt me dicati o ns  
•  A Es  
6. 2. 5  
L o n g -ter m F oll o w -u p   
L o n g -ter m F oll o w-u p will start at Bas eli ne f or e nr olle d s u bjects w h o ha ve bee n per m a ne ntl y 
disc o nti n ue d fr o m bel u m os u dil i n St u d y K D 0 2 5 -2 0 8 or i n St u d y K D 0 2 5 -2 1 3 w here t he y ha ve 
n ot yet ha d a n F F S  e ve nt.  T he L T F U  will occ ur a fter t he 2 8-da y F oll o w -u p Visit has bee n 
c o m plete d f or e nr olle d s u bjects w h o  were acti vel y d os e d wit h bel u m os u dil at Baseli ne.   
S u bjects will ha ve L T F U  a p pr o xi matel y e ver y 3 m o nt hs u ntil a n F F S  e ve nt occ urs.  T his L T F U 
assess me nt will occ ur b y s u bjects bei n g c o ntact e d b y tele p h o n e, e -m ail, or p ostal mail t o c o nfir m 
s ur vi val stat us, a n y i nitiati o n of ne w s yst e mic c G V H D t hera pies, a n d rela pse of u n derl yi n g 
disease.  Alter nati vel y, t his  i nf or mati o n ma y be o btai ne d fr o m t he s u bject’s me dical rec or ds. 
6. 2. 6  
U nsc he d ule d Visit   
T he assess me nts a n d pr oce d ures p erf or me d at a n y u nsc he d ule d visit will de pe n d o n t he cli nical 
ju d g me nt of t he I n vesti gat or . 
6. 3  Effic ac y  E n d p oi nts   
T he efficac y e n d p oi nts of t his st u d y will be:  
•  D urati o n of Res p o nse  (D O R )  
•  C ha n ge i n L S S  (A p p e n di x  D: Lee c G V H D S y m pt o m Sc ore ) 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
•  Ti me t o Ne xt Treat me nt  ( T T N T):  defi ne d as t he ti me fr o m t he first d ose of bel u m os u dil 
t o t he start of a d diti o nal s yste mic c G V H D t h era p y 
•  F F S:   defi n e d a s t he a bs e nce of c G V H D tr eat me nt c ha n ge, n o n-rela ps e m ortalit y, a n d 
rec urre nt mali g na nc y  
•  O verall S ur vi val ( O S):  d efi ne d as t he ti me fr o m first d ose of bel u m os u dil t o t he date of 
deat h d ue t o a n y ca use  
•  Perce nta ge of s u bjects w h o ha ve a b est res p o nse of C R  a n d perce nta ge  of s u bjects w h o 
ha ve a b est res p o nse of P R  
•  Res p o nse b y in di vi d ual o r ga n 
•  C ha n ge i n cortic oster oi d d ose:  t he c ha n ge i n pre d nis o ne e q ui vale nt d ose of 
c ortic oster oi ds ( m g/ k g/ da y) d uri n g t he st u d y   
•  C ha n ge i n c G V H D Gl o b al Se verit y R ati n g usi n g t he Cli nicia n-re p ort e d Gl o bal c G V H D 
Acti vit y Ass ess me nt  (A p pe n di x  B: Cli nicia n -re p orted Gl o bal c G V H D Acti vit y 
Assess me nt ) 
6. 4  S afet y  E n d p oi nts   
T he f oll o w -u p safet y e n d p oi nts of t his st u d y will b e o btai ne d at r e g ular i nter vals a n d will 
i ncl u de: 
•  A Es  
•  Gra de ≥ 3 A Es  
•  S A Es  
•  Deat hs  
•  P Es  
•  Vital si g ns  
•  Cli nical la b orat or y e val u ati o ns  
o  He mat ol o gi c:  w hite bl o o d cell c o u nt wit h differe ntial, re d bl o o d cell c o u nt, 
he m o gl o bi n, he mat o crit, platelet c o u nt, a n d mea n c or p usc ular v ol u me  
o  Ser u m c he mistr y:  al b u mi n, al kali ne p h os p hatase, A L T, A S T, bl o o d urea 
nitr o ge n , Ca, Cl, C O2, creati ni ne/ gl o mer ular filtratio n rate  (A p pe n di x  F : 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
E q uati o ns t o Pre dict Gl o mer ular Filtrati o n Rate ( M D R D -4) , creati ni ne 
p h os p h o ki nase , t otal a n d direct bilir u bi n, ga m ma gl uta m yl transferas e, 
gl o b uli n, gl u c ose, lact ate de h y dr o ge nas e, M g, P, K, Na, t otal pr otei n, a n d uric 
aci d  
o  Pre g n a nc y testi n g: uri ne pre g na nc y t ests will be d o ne i n fe males of 
c hil d beari n g p ote ntial.  P ositi ve uri ne res ults will  be c o nfir me d wit h ser u m 
testi n g.  If preg na n c y is c o nfir me d wit h ser u m testi n g, bel u m os u dil will be 
disc o nti n ue d . 
•  E C Gs  
T he A E re p orti n g peri o d f or a s u bject e nr olle d i n t he st u d y will be gi n w he n t he s u bject si g ns t he 
I C F a n d c o nti n ues  t hr o u g h t he 2 8-da y F oll o w -u p Visit, i.e., 2 8 da ys after t he l ast d ose of 
bel u m os u dil.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
7  S A F E T Y   
7. 1  S afet y P ar a meters   
T he C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts versi o n 4. 0 3  (C T C A E v 4. 0 3 ) will be 
use d f or classif yi n g la b orat or y res ults a n d gra di n g  A Es .  S u bjects will be m o nit ore d t hr o u g h o ut 
t he treat me nt a n d f oll o w-u p peri o d f or occ urre nce of A E s (ac ute, dela ye d, a n d/or c u m ulati ve) as 
well as f or c h a n ges i n cli nical stat us, vital si g n meas ure me nts, a n d la b orat or y d ata.  Safet y 
para meters t o be meas ure d/assesse d i ncl u de vital si g n meas ure me nts ; P E ; he mat ol o g y  a n d ser u m 
c he mistr y  res ults; a n d E C G  rec or di n gs. 
7. 2  A d verse E ve nt  D efi niti o n   
A n A E is defi n e d as a n y u nt o war d me dical o cc urre nce i n a cli nical trial s u bject ass ociate d wit h 
t he use of a dr u g, w het her or n ot c o nsi dere d dr u g-relate d.  A n A E  ca n b e a n u nfa v ora bl e a n d 
u ni nte n de d si g n (e .g ., a n a b n or mal la b orat or y val u e fi n di n g), a s y m pt o m, or a disease te m p orall y 
ass ociate d wit h t he use of a dr u g, wit h o ut j u d g m e nt as t o ca usalit y.  A n A E ca n aris e fr o m use of 
t he dr u g (e.g ., us e i n c o m bi nati o n wit h a n ot her dr u g) a n d fr o m a n y r o ute of a d mi nistrati o n, 
f or m ulati o n or d ose, i ncl u di n g a n o v er d ose.  A n A E als o i ncl u des, b ut is n ot li mite d t o, a n y 
cli nicall y si g nifica nt w orse ni n g of a pre -e xisti n g c o n diti o n.   E x a m ples i ncl u de:  
•  A n y si g n, s y m pt o m, p h ysi cal fi n di n g, or l a b orat or y res ult t hat has w orse n e d i n nat ure, 
se verit y or fre q ue n c y c o m pare d t o Baseli ne  
•  Reacti o ns fr o m a n i n vesti gati o nal pr o d u ct i ncl u di n g t h ose o cc urri n g as a res ult of a n 
o ver d ose, a b us e of t he st u d y dr u g, wit h dra wal p h e n o me na, se nsiti vit y or t o xicit y  
•  C o nc urre nt ill ness t hat w as n ot prese nt or w orse ns i n nat ure, se verit y, or fre q ue nc y 
c o m pare d t o Baseli ne   
•  I nj ur y or acci de nt a n d/ or 
•  E x acer bati o n of a pre -e xisti n g c o n diti o n  
F or t he p ur p os e of dat a c ollecti o n, all u nt o war d e v e nts t hat occ u r after i nf or me d c o nse nt t hr o u g h 
t he 2 8-da y F oll o w -u p Visit  are t o be rec or de d o n e C R Fs b y t he i n vesti gati o nal site.   
7. 3  E v al u ati n g A d verse E ve nts   
T he I n vesti gat or will det er mi ne t he seri o us n ess, i nte nsit y, a n d ca us alit y of A E s bas e d o n t he 
defi niti o ns t hat f oll o w.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 4 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
7. 3. 1  
Seri o us A d verse E ve nts   
T he S p o ns or  or desi g nee m ust be n otifie d wit hi n 2 4 h o urs.  
T he S A E defi niti o n a n d re p orti n g re q uire m e nts will be i n  acc or da nce wit h Title 2 1 Part C o de of 
Fe deral Re g ulati o ns ( C F R ) 3 1 2. 3 2 a n d t he G ui da nce f or I n d ustr y a n d I n v esti gat ors Safet y 
Re p orti n g Re q uir e me nts f or I n vesti gati o nal N e w Dr u g (I N Ds) a n d 
Bi oa vaila bilit y /Bi oe q ui v ale nce  St u dies  ( B A/ B E). 
S A E: A n a d verse e v e nt is c o nsi dere d "seri o us" if, i n t he vie w of eit her t he I n vesti gat or or 
S p o ns or , it res ults i n a n y of t he f oll o wi n g o ut c o mes: 
•  Deat h:   T his i ncl u des a n y deat h t hat occ urs w hile t he s u bject is “o n st u d y ” as well as a n y 
deat h t hat occ urs wit hi n 2 8 da ys after st u d y dr u g disc o nti n uati o n .  N ote:  Deat h is a n 
o utc o me of a n A E, n ot a n A E i n itself.  T he e ve nt(s) t hat ca use d d eat h ( e. g., ill nes s, 
acci de nt) is t he S A E.  D eat h d ue t o a n y ot her ca us e(s) m ust als o be re p orte d as a n 
o utc o me of t he re p orta bl e S A E.  
•  Lif e -t hreate ni n g A E :  A n A E or s us pecte d a d verse reacti o n is c o nsi dere d 
“life-t hreate ni n g” if, i n t h e vie w of eit her t he I n v esti gat or or S p o ns or , its occ urre n ce 
places t he s u bje ct at i m me diate ris k of deat h.   It d oes n ot i ncl u de a n A E or s us pecte d 
a d verse reacti o n t hat, ha d it occ urre d i n a m ore se v ere f or m, mi g ht ha ve ca use d deat h .  
•  I n p atie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n:  T he I n vesti gat or 
s h o ul d n ot re p ort h os pitalizati o n or pr ol o n gati o n of h os pitalizati o n i n t he f oll o wi n g 
sit uati o ns: ( 1) hos pitaliz ati o n or pr ol o n gati o n of h os pitalizati o n is nee de d f or a pr oce d ure 
re q uire d b y t he pr ot oc ol; ( 2) h os pitalizati o n o r pr ol o n gati o n of h os pitalizati o n is part of 
r o uti ne pr oce d ure f oll o w e d b y st u d y ce nter; or ( 3) h os pitalizati o n f or s ur ve y visits or 
a n n ual p h ysicals.  N ote: a  h os pitalizati o n pla n ne d bef ore t h e start of t he st u d y f or a 
pre -e xisti n g c o n diti o n w hic h has n ot  w orse n e d d o es n ot c o u nt as a n S A E .  
•  Persiste nt or si g nifica nt i nca pacit y or s u bsta ntial disr u pti o n of t he a bilit y t o c o n d uct 
n or mal life f u ncti o ns  
•  C o n ge nital a n o mal y/ birt h defect  
•  I m p ort a nt me dical e v e nt:  A n e ve nt t hat ma y n ot res ult i n deat h, be life -t hr eate ni n g, or 
re q uire h os pitaliz ati o n ma y b e c o nsi dere d seri o us w he n, base d u p o n a p pr o priate me dical 
j u d g me nt, it ma y je o par diz e t he s u bject a n d ma y re q uire me dical or s ur gical i nter ve nti o n 
t o pre ve nt o ne  of t h e o utc o mes liste d i n t his defi niti o n.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
7. 3. 2  
Pr ot oc ol -R el ate d A d ve rse E ve nts   
A d verse e ve nts  t hat are n ot st u d y dr u g relate d ma y ne vert heless b e c o nsi dere d b y t h e 
I n v esti gat or or t he m e di cal m o nit or t o be relate d t o t he c o n d uct of  t he cli nical st u d y, i.e., t he 
e ve nt ma y be relate d t o t he fact t hat a s u bject is p artici pati n g i n t he st u d y.  F or e x a m ple, a 
pr ot oc ol -relat e d A E  m a y be a n e v e nt t hat occ urs d uri n g a was h o ut peri o d or t hat is relate d t o a 
pr oce d ure re q uire d b y t h e pr ot oc ol . 
7. 3. 3  
Rel ati o ns hi p t o St u d y Dr u g   
T he I n vesti gat or will atte m pt t o assess t he relati o ns hi p of t he e ve nt  t o st u d y dr u g usi n g a 5-p oi nt 
scale (n ot relate d, u nli kel y-relate d, p ossi bl y rel ate d, pr o ba bl y relat e d, or defi nitel y relate d; 
(A p pe n di x  G : Deter mi ni n g Relati o ns hi p of  A Es t o St u d y Dr u g ). 
7. 3. 4  
Rec or d i n g A d verse E ve nts  
All A E s a n d S A Es  are t o be acc uratel y rec or de d o n t he A d verse E ve nt p a ge of t he s u bject ’s 
e C R F d uri n g t he s u bject’s partici pati o n i n t he st u d y.  T he se verit y of eac h A E  will be gra de d 
usi n g t he C T C A E v 4. 0 3  scale.  T h e date of o ns et as well as t he e n d d ate of t he e ve nt als o s h o ul d 
be rec or de d  or t h e e ve nt s h o ul d be e ntere d as “o n g oi n g ”.  I n a d diti o n, t he met h o d use d t o treat 
t he A E  a n d t h e o utc o me o f t he A E  als o will be n ote d.  I n t he e v e nt t hat t he gra de of a n A E  
w orse ns , a n e n d date s h o ul d be e ntere d t o t he i niti al A E a n d a ne w A E e ntere d wit h t he u p date d 
gra de a n d d ate of o ns et.  T he I n vesti gat or will ass ess t he relati o ns hi p of t he e ve nt t o st u d y dr u g.    
N ote: All S A Es als o are t o be e ntere d o nt o a n S A E f or m a n d se nt t o t he S p o ns or  or desi g nee  
wit hi n 2 4 h o urs . 
7. 3. 5  
Seri o us A d verse E ve nt Re p orti n g   
7. 3. 5. 1  
Ti mefr a me  f or Re p orti n g  
A n y d eat h, S A E , or  pre g na nc y  (i ncl u di n g pre g na n c y of a part ner) e x perie n ce d b y a s u bject w hile 
recei vi n g or wit hi n 2 8 da ys of recei vi n g st u d y dr u g, re gar dl ess of rel ati o ns hi p t o  st u d y dr u g, 
i ncl u di n g f oll o w-u p i nf or mati o n,  or a n y S A E t h at occ urs m ore t h a n 2 8 da ys after recei vi n g st u d y 
dr u g, a n d is belie ve d t o b e st u d y dr u g -rel ate d, m ust be pr o m ptl y re p orte d ( wit hi n 2 4 h o urs of t he 
I n v esti gat or bec o mi n g a ware of t he e v e nt) b y e -ma il t o t he S p o ns or  ( or desi g nee). 
S A E F or m o r Pre g n a nc y F or m (i niti al re p ort or f oll o w-u p re p ort) m ust be se nt 
wit hi n 2 4 h o urs  of bec o mi n g a w are t o:  cli nic al S A Ere p orti n g @ K a d m o n.c o m . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A d diti o nall y, t he I n vesti gat or will be a ble t o c o ntact t he m e dical m o nit or at all ti mes .  Refer t o 
s p o ns or a n d C R O c o ntact list f or u p t o date c o ntact i nf or mati o n. 
7. 3. 5. 2  
S A E I nf or m ati o n t o be Pr o vi de d b y t he I n vesti g at or  
T he S A Es  f or all e nr olle d s u bjects m ust be rec or de d o n t he S A E f or m  ( d uri n g st u d y 
partici pati o n) .  T his re q uire me nt i ncl u des all S A Es t hat occ ur after i nf or me d c o nse nt a n d t hr o u g h 
t he 2 8-da y F oll o w -u p Visit at 2 8  da ys after last d os e of st u d y dr u g .  In a d diti o n, a n y S A Es t hat 
are ass esse d as at least p ossi bl y relate d t o st u d y dr u g  b y t h e I n vesti gat or, e ve n if t he S A E occ urs 
m ore t ha n 2 8 da ys after t he last d ose of st u d y dr u g , m ust be re p orte d t o t he Ka d m o n 
P har mac o vi gila nce ( or d esi g nee)  as descri b e d bel o w:  
Re p ort S A Es o n a n S A E f or m wit hi n 2 4 h o urs of bec o mi n g a w are t o:  
cli nic al S A Ere p orti n g @ K a d m o n.c o m . 
A d diti o n all y, t he I n vesti g at or will be a ble t o c o nt act t he me dic al m o nit or at all ti mes at:  
A. Wo olf re y @ me d p ace. c o m . 
T he mi ni m u m i nf or mati o n re q uire d f or S A E re p orti n g i ncl u des i de ntit y of I n vesti gat or, site 
n u m ber, s u bject n u m ber, a n e ve nt des cri pti o n, S A E ter m(s), o nset dat e, reas o n w h y t he e ve nt is 
c o nsi dere d t o  be s eri o us ( i.e., t he seri o us ness criteria), a n d t he I n v esti gat or’s assess me nt of t he 
relati o ns hi p of t he e ve nt t o st u d y dr u g .  A d diti o nal S A E i nf or mati o n i ncl u di n g me dicati o ns or 
ot her t hera p e utic meas ures use d t o treat t he e ve nt, acti o n ta ke n wit h t he st u d y dr u g  d u e t o t he 
e ve nt, a n d t he o utc o m e/r es ol uti o n of t he e ve nt will be rec or de d o n t he S A E f or m .  F or ms f or 
re p orti n g S A E will be pr o vi de d t o t he st u d y sites. 
W he n re p orti n g S A E, t he f oll o wi n g a d diti o nal p oi nts s h o ul d be n ote d:  
•  W he n t he dia g n osis of a n S A E is k n o w n or s us pecte d, t he I n vesti gat or s h o ul d re p ort t he 
dia g n osis or s y n dr o m e as t he pri mar y S A E ter m, r at her t ha n as si g ns or s y m pt o ms . Si g ns 
a n d s y m pt o ms ma y t he n be descri b e d i n t he e ve nt descri pti o n .  F or e x a m ple, d ys p nea 
s h o ul d n ot be use d as a n S A E ter m if t he dia g n osis w hic h ca use d t h e d ys p n ea is k n o w n t o 
be m ali g n a nt p le ural eff usi o n.   
•  Deat h s h o ul d n ot be re p orte d as a n S A E b ut as a n o utc o me of a s pecific S A E, u nless t he 
e ve nt prece di n g t he deat h is u n k n o w n .  I n t he e x ce pti o nal case w here t he e ve nts lea di n g 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
t o deat h are u n k n o w n, t he n d eat h ma y b e use d as a n e ve nt ter m .  If a n a ut o ps y was 
perf or me d, t h e a ut o ps y re p or t s h o ul d be pr o vi de d.  
W hile m ost h os pitaliz ati o ns necessitate re p orti n g a n S A E, s o me h os pitalizati o ns d o n ot re q uire 
S A E re p orti n g: ( 1) ele cti ve or pre vi o usl y sc h e d ule d s ur ger y (e.g ., a pre vi o usl y sc he d ul e d ve ntral 
her nia re pair ); ( 2) pr oce d ures f or pre-existi n g c o n diti o ns t hat ha ve n ot w orse ne d aft er i nitiati o n 
of treat me nt ; ( 3) pre-s p ecifie d st u d y hos pitalizati o ns f or o bser vati o n ; a n d ( 4) eve nts t hat res ult i n 
e mer ge n c y r o o m sta ys of less t ha n 2 4 h o urs a n d t h at d o n ot re q uire a d missi o n. 
H o we ver, S A E s m ust be re p orte d f or a n y s ur gical or pr oce d ural c o m plicati o n res ulti n g i n 
pr ol o n gati o n of t h e h os pitaliz ati o n.  
I n all cases, t he I n vesti gat or s h o ul d c o nti n ue t o m o nit or t he cli nical sit uati o n a n d re p ort all 
material facts relati n g t o t he pr o gressi o n or o ut c o me of t he S A E as a f oll o w -u p i n t he sa me 
ti mefra me a n d ma n ner as t he i nitial S A E re p ort.  F urt her m ore, t he I n vesti gat or ma y b e re q uir e d 
t o pr o vi de s u p ple me ntar y i nf or mati o n as re q u este d b y t he Ka d m o n P har mac o vi gila nce or 
desi g nee.  
Re p ort f oll o w -u p S A E i n f or m ati o n wit hi n 2 4 h o urs of bec o mi n g a w are t o: 
cli nic al S A Ere p orti n g @ K a d m o n.c o m . 
7. 3. 5. 3  
Pre g n a nc y   
Pre g n a ncies o cc urri n g i n s u bject s e nr olle d i n a st u d y or i n a fe mal e part ner of a male st u d y 
partici pa nt m ust be re p orte d a n d f oll o we d t o o utc o me.  If a fe male s u bject i na d verte ntl y bec o mes 
pre g na nt w hile o n st u d y treat me nt, t he s u bject will i m me diatel y be re m o ve d fr o m t he st u d y.  A n y 
pr e g na nci es of fe male st u d y s u bjects a n d part ners of male st u d y s u bject t hat occ ur wit hi n 
1 2 0  da ys f oll o wi n g t he l ast d ose of st u d y tr eat me nt m ust be ca pt ure d i n t he e C R F.  
T he I n vesti gat or s h o ul d c o m plete t he initial Pre g n a nc y  Re p ort  F or m a n d f or war d it t o t he 
S p o ns or ( or desi g nee) wit hi n 2 4 h o urs of bec o mi n g a ware of t he pre g na n c y as descri be d i n 
Secti o n  7. 3. 5. 1  of t he pr ot oc ol.  If t here is a n ass ociate d seri o us o utc o me, t h e n b ot h t he initial 
Pre g n a nc y R e p ort F or m a n d S A E Re p ort F or m s h o ul d be c o m plete d.  
T he site will f oll o w -u p wit h t he s u bject at least m o nt hl y a n d d oc u m e nt t he s u bject ’s stat us u ntil 
t he pre g na n c y has bee n c o m plete d or ter mi nate d.  T he In vesti gat or will ma ke e ver y eff ort t o 
o btai n per missi o n t o f oll o w t he o utc o me of t he pre g n a nc y a n d re p ort t he c o n diti o n of t he fet us or 
ne w b or n t o t he S p o ns or .  T he Pre g na n c y Re p ort  F or m s h o ul d be u p date d a n d s u b mitte d t o t he 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
S p o ns or  wit hi n 2 4 h o urs of bec o mi n g a ware of t he pre g na nc y o ut c o me.  If a n S A E occ urre d, 
t he n t he S A E Re p ort F or m m ust be c o m plete d a n d s u b mitte d as well. 
I n t he e ve nt t he pre g na n c y o utc o me o cc urs f oll o wi n g t he e n d of t he st u d y a n d data base l oc k, t h e 
I n v esti gat or will re p ort t he pre g na n c y o utc o me t o t he S p o ns or ( or desi g nee) wit hi n 2 4 h o urs after 
t he o utc o me of t he pre g n a nc y is k n o w n t o t he I n v esti gat or i n acc or da nce wit h t he pr oce d ure f or 
re p orti n g S A Es (Secti o n  7. 3. 5. 1 ). 
Pre g n a nc y al o n e is n ot re gar de d as a n A E u nless t here is a p ossi bilit y t hat t he st u d y dr u g m a y 
ha ve i nterfere d wit h t he effecti ve ness of a c o ntrace pti ve me dicati o n.   Electi ve a b orti o ns wit h o ut 
c o m plicati o ns s h o ul d n ot be c o nsi dere d A Es u nless t he y were t h era p e utic a b orti o ns b ut s h o ul d be 
re p orte d t o t he S p o ns or.  H os pitalizati o n f or n or mal deli ver y of a healt h y n e w b or n s h o ul d n ot be 
c o nsi dere d a n S A E.  Pre g na n c y is n ot c o nsi dere d a n S A E u nles s t here is a n ass ociate d seri o us 
o utc o me. S p o nta ne o us a b orti o ns s h o ul d al wa ys b e re p ort e d as S A Es.  
A n y S A E t hat o cc urs d uri n g pre g n a nc y m ust be rec or de d o n t he S A E Re p ort F or m (e .g ., 
mater nal seri o us c o m plicati o ns, t hera pe utic a b orti o n, ect o pic pre g n a nc y, still birt h, ne o natal 
deat h, c o n ge nital a n o mal y, birt h defect) a n d re p ort e d wit hi n 2 4 h o urs i n acc or da nce wit h t he 
pr oce d ure f or re p orti n g S A Es.  
T he Pre g na n c y Re p ort F or m  a n d a n y relate d S A E Re p ort F or ms m ust be re p orte d t o t he S p o ns or 
as o utli ne d f or S A Es i n Secti o n  7. 3. 5. 2 . 
7. 3. 5. 4  
Re g ul at or y Re p orti n g   
Ka d m o n P har mac o vi gila nce ( or d esi g n ee) will s u b mit S A E s t hat meet t he criteria f or e x pe dite d 
re p orti n g t o t he Re g ulat or y A ut h orities i n acc or da nce wit h l ocal r e g ulati o ns g o ver ni n g s afet y 
re p orti n g.  Re p orti n g of S A E s b y t he I n v esti gat or t o his or her I R B/I E C will be d o ne i n 
acc or d a nce wit h t he sta n dar d o perati n g pr oce d ures a n d p olicies of t he I R B /I E C.  A de q u ate 
d oc u me ntati o n m ust be mai ntai ne d s h o wi n g t hat t he I R B /I E C was pr o perl y n otifie d.  
7. 4  Ot her S afet y C o nsi der ati o ns   
7. 4. 1  
L a b or at or y D at a   
All la b orat or y data o bt ai ne d d uri n g t he c o urse of t he st u d y  s h o ul d be re vie we d.  A n y a b n or mal 
val ue t hat lea ds t o a c ha n ge i n s u bje ct ma na ge m e nt ( e.g ., d os e re d ucti o n or dela y, re q uire me nt 
f or a d diti o nal me dicati o n or m o nit ori n g) or is c o nsi dere d t o be of cli nical si g nifica nce b y t h e 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
I n v esti gat or s h o ul d be re p orte d as a n A E a n d/or S A E  as a p pr o priate, u nless t his val ue is 
c o nsiste nt wit h t he s u bject ’s prese nt disease state or is c o nsiste nt wit h val ues o btai ne d bef ore  
e ntr y i nt o t he st u d y.  
La b orat or y res ults will be classifie d usi n g t he C T C A E v 4. 0 3 . 
7. 4. 2  
F oll o w -U p of A d verse E ve nts   
All  S A E s a n d T E A Es  (i n cl u di n g cli nicall y si g nifica nt a b n or mal la b orat or y val ues t hat meet t hese 
criteria) will be f oll o we d u ntil eit her res ol uti o n of t he e ve nt or d eter mi nati o n b y t he I n vesti gat or 
t hat t he e ve nt has bec o m e sta ble or irre versi ble.  T he stat us of all ot her c o nti n ui n g A Es will be 
d oc u me nte d as of 2 8 d a ys after last d ose of st u d y dr u g .   
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
8  S T U D Y S T O P PI N G R U L E S   
T here are n o st o p pi n g r ul es f or t his st u d y.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
9  S T A TI S TI C A L C O N SI D E R A TI O N S   
9. 1  H y p ot hesis   
T his will be a l o n g -ter m f oll o w-u p st u d y of t h e efficac y a n d safet y of s u bjects treate d wit h 
bel u m os u dil i n St u d y K D 0 2 5 -2 0 8 a n d St u d y K D 0 2 5 -2 1 3.  N o f or mal h y p ot hesis will be  use d.  
9. 2  S a m ple Size  a n d P o w er C alc ul ati o n   
N o f or mal p o wer calc ulati o n will be  perf or me d t o deter mi ne t he st u d y sa m ple size.  
9. 3  A n al ysis P o p ul ati o ns   
T he p o p ulati o ns f or  efficac y a n d safet y a n al ys es will be t he  F ull A nal ysis S et c o nsist i n g of all 
s u bjects e nr olle d i n t he st u d y. 
T here are 3  tr eat me nt gr o u ps f or t his st u d y: bel u m os u dil 2 0 0 m g Q D, 2 0 0 m g BI D, a n d 4 0 0 m g 
Q D.  Eac h s u bject ’s treat me nt gr o u p is det er mi ne d b y t heir ori gi n all y assi g ne d d osi n g c o h ort 
(St u d y K D 0 2 5 -2 0 8) or ra n d o mize d ar m (St u d y K D 0 2 5 -2 1 3).  
9. 4  S u b gr o u p A n al yses   
N o s u b gr o u p a nal ysis will be c o n d ucte d.  
9. 5  D at a A n al ysis   
All pre -s pecifie d a n al ys es will be descri be d i n a Statistical A nal ysis Pla n.  
9. 6  I nteri m A n al ysis  
A n i nteri m a nal ys is will be perf or me d w he n all s u bjects ha ve c o m plet e d at least 3 years of 
treat me nt wit h bel u m os u dil or wit h dre w earlier ( n ot i ncl usi ve of t he c o m pa ni o n st u d y s u bjects). 
9. 7  Effic ac y A n al yses   
T he f oll o w -u p efficac y e n d p oi nts i n t his st u d y are descri be d i n Secti o n  6. 3 . 
9. 8  E x pl or at or y A n al yses   
N o e x pl orat or y a nal yses will be c o n d ucte d.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
9. 9  S afet y A n al yses   
Safet y a nal yses will be perf or me d o n all s u bjects w h o recei ve at least o ne d ose of bel u m os u dil.   
A d verse e ve nt s will be c o de d usi n g t he M e dical Dicti o nar y of Re g ulat or y Acti vities ( Me d D R A ) 
( Versi o n 24 . 0 or greater).  T he n u m ber a n d perce nt a ges of s u bjects e x perie nci n g T E A Es will be 
ta b ulate d b y S yste m Or ga n Class a n d Preferre d Ter m ( P T) .  T he n u m b er of e ve nts b y P T  will 
als o be s u m marize d.  Ta b ulati o n b y ma xi m u m se verit y a n d rel ati o ns hi p t o treat me nt will als o b e 
i ncl u de d b y tr eat me nt gr o u p. 
S u m mar y s u bject listi n g will be pr o vi de d f or S A Es, A Es res ulti n g i n st u d y disc o nti n uati o n, a n d 
deat hs.  
A d verse e ve nts, S A Es, relate d A Es, r elate d S A Es, Gra de ≥ 3 A Es, relate d Gra de ≥ 3 A Es, a n d 
A Es lea di n g t o wit h dra w al a n d t reat me nt disc o nti n uati o n, a n d deat hs will be s u m marize d.  
La b orat or y res ults will be s u m mariz e d b y tr eat me nt gr o u p , inci de nce of la b orat or y 
a b n or malities , a n d w orst o n -st u d y gra de d uri n g t h e treat me nt peri o d will be s u m marize d. T he 
i nci de nce of Gra d e ≥ 3 la b orat or y a b n or malities u n der treat me nt a n d s hifts i n t o xicit y gra di n g 
fr o m Bas eli ne  t o hi g h est gra de p ost-bas eli ne will be dis pla ye d.  
Vital si g n meas ur e me nts a n d E C Gs will be s u m marize d b y treat me nt gr o u p at eac h s c he d ule d 
ti me p oi nt usi n g descri pti ve statistics a n d i ncl u de d i n data listi n gs.  
9. 1 0  P h ar m a c o ki netic A n al yses   
N o P K assess me nts f or a nal ysis will be perf or me d i n t his st u d y.  
9. 1 1  P h ar m a c o d y n a mi c A n al yses   
N o p har mac o d y na mic assess me nts f or a nal ysis will be perf or me d i n t his st u d y.  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 0  D A T A Q U A LI T Y  A S S U R A N C E   
Acc urate a n d relia ble dat a c ollecti o n will be e ns ure d b y v erificati o n a n d cr oss-c hec ki n g of t h e 
e C R Fs a gai nst t he I n vesti gat or’s rec or ds b y t he st u d y m o nit or (s o urce d oc u me nt verificati o n) 
a n d b y t h e mai nte na n ce of a dr u g – dis pe nsi n g l o g b y t he I n v esti gat or.  C ollecte d data will be 
e ntere d i nt o a c o m p uter data base a n d s u bject t o electr o nic a n d ma n ual q ualit y ass ura nce 
pr oce d ures.  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 5 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 1  R E G U L A T O R Y O B LI G A TI O N S  & C O M P LI A N C E S T A T E M E N T   
T his st u d y will be c o n d u cte d i n c o m plia nce wit h G C P, i ncl u di n g I nter nati o nal C o nfere n ce o n 
Har m o nisati o n of Tec h ni cal Re q uire me nts f or Re gistrati o n of P har m ace uti cals f or H u ma n Use, 
a n d i n ge neral, c o nsiste nt wit h t he m ost rece nt versi o n of t he Declarati o n  of Helsi n ki.  I n 
a d diti o n, t he I n v esti gat or will a gree  t o a d here t o all a p plica ble l ocal la ws a n d re g ulat or y 
re q uire me nts r ele va nt t o t he use of ne w t h era p e utic a ge nts i n t he c o u ntri es i n v ol ve d. 
T he st u d y will  be c o n d ucte d i n c o m plia nce wit h t he pr ot oc ol.  
Freel y gi v e n writte n i nf or me d c o nse nt m ust be o btai ne d fr o m e ver y s u bject bef ore p artici pati o n 
i n t his cli nical trial.  T he ri g hts, safet y, a n d well -b ei n g of partici pati n g s u bj ects are t he m ost 
i m p orta nt c o nsi derati o ns a n d s h o ul d pre vail o ver i nterests of scie nce a n d s o ciet y. 
St u d y p ers o n nel i n v ol ve d i n c o n d ucti n g t his trial will be q ualifie d b y e d ucati o n, trai ni n g, a n d 
e x perie nce t o perf or m t h eir res pecti ve tas k(s).  T his trial will n ot use t he ser vices of st u d y 
pers o n nel w here sa n cti o ns ha ve bee n i n v o k e d  or w here t here has b ee n sci e ntific misc o n d uct of 
fra u d (e. g., l oss of me dic al lice ns ure, d e bar me nt). 
 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 2  E T HI C A L A S P E C T S   
1 2. 1  L oc al Re g ul ati o ns   
T he st u d y m ust f ull y a d h ere t o t he pri n ci ples o utli ne d i n “G ui deli ne f or G o o d Cli nical Practice ” 
I C H E 6( R 2) I nte grate d A d de n d u m t o I C H E 6( R 1) ( Marc h 2 0 1 8), a n d i n ge n eral, be c o n d ucte d i n 
a ma n ner c o nsiste nt wit h t he  m ost rece nt versi o n of t he Decl arati o n of Helsi n ki .  T he 
I n v esti gat or will e ns ure t hat t he c o n d uct of t he st u d y c o m plies wit h t he basi c pri nci ples of G C P 
as o utli ne d i n t he c urre nt versi o n of 2 1  C F R, S u b part  D, Part  3 1 2, “Res p o nsi bilities of S p o ns ors 
a n d I n vesti gat ors”, Part  5 0, “Pr otecti o n of H u ma n S u bjects ”, a n d Part 5 6, “I nstit uti o nal Re vie w 
B oar ds ”, or a p plica ble l o cal e q ui vale nt . 
1 2. 2  I nf or me d C o nse nt  
Sa m ple I C Fs  will be s u p plie d  t o eac h site. 
It is t he res p o nsi bilit y of t he I n v esti gat or, or a pers o n desi g n ate d b y t he I n v esti gat or, t o o btai n 
writte n i nf or me d c o ns e nt fr o m eac h s u bject ( or t h e s u bject ’s le gall y a ut h orize d re prese ntati ve) 
partici pati n g i n t his st u d y after a de q uat e e x pla nati o n of t he ai ms, met h o ds, a ntici pate d be nefits, 
a n d p ote ntial hazar ds of t he st u d y  i n acc or da nce wit h a p plica ble fe d eral a n d state re g ulati o ns.  I n 
t he case w h ere t he s u bject is u na ble t o rea d, a n i m partial wit ness s h o ul d be prese nt d uri n g t he 
e ntire i nf or me d c o nse nt disc ussi o n.  After t he s u bject has orall y c o ns e nte d t o partici pati o n i n t he 
trial, t he wit ness’ si g nat ure o n t he f or m will attest t hat t he i nf or mati o n i n t he c o nse nt f or m was 
acc uratel y e x plai ne d a n d u n derst o o d .  A c o p y of t h e I C F  m ust be  pr o vi de d t o t he s u bject or t o t he 
s u bject’s le gall y a ut h orize d re prese ntati ve.  If a p plica ble, it will be pr o vi de d i n a certifie d 
tra nslati o n of t he l ocal la n g ua ge. 
T he e C R F f or t his st u d y c o ntai ns a secti o n f or d oc u me nti n g i nf or me d s u bject c o nse nt, a n d this 
m ust be c o m plete d a p pr o priatel y .  Si g n e d I C Fs  m ust re mai n i n eac h s u bject ’s st u d y file a n d b e 
a vaila ble f or verific ati o n b y st u d y m o nit ors at a n y ti me .  If ne w safet y i nf or mati o n res ults i n 
c ha n ges i n t he ris k/ be n efit assess me nt, t he I C F s h o ul d be re vie we d a n d u p date d as necessar y.  
All s u bjects (i ncl u di n g t h ose alrea d y bei n g treate d) s h o ul d be i nf or me d of t he ne w i nf or m ati o n, 
s h o ul d be gi ve n a c o p y of t he re vise d f or m, a n d s h o ul d gi ve t heir c o nse nt t o c o nti n ue i n t he 
st u d y. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 2. 3  Rese arc h Et hics C o m mittees   
Pri or t o t he i nitiati o n of t he st u d y, t he pr ot oc ol a n d ass ociate d d oc u me ntati o n m ust be gi ve n a fa v ora ble 
o pi ni o n a n d/ or a p pr o val b y a n Et hic C o m mittee a n d/ or a n I nstit uti o nal Re v ie w B oar d.  A c o p y of t his 
writte n a p pr o val a n d a n y c orres p o n de nce wit h t he E C/I R B will be pr o vi de d t o t he S p o ns or . 
1 2. 4  F ut ure Use of S u bject S a m ples   
A ll of t he bl o o d c o m p o ne nts o btai ne d d uri n g t his st u d y ma y be re q uire d f or t he tests t hat are p art 
of t he cli nical trial .   
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 3  C O N DI TI O N S F O R M O DI F YI N G T H E P R O T O C O L   
Pr ot oc ol m o dificati o ns will be re vie we d a n d a p pr o ve d b y Ka d m o n C or p orati o n  re prese nt ati ves. 
All pr ot oc ol m o dificati o ns m ust be s u b mitte d t o t he I R B/I E C f or i nf or mati o n a n d a p pr o val i n 
acc or da nce wit h l ocal re q uire me nts, a n d t o re g ulat or y a ge ncies if re q uir e d.  A p pr o val m ust be 
o btai ne d bef ore a n y c ha n ges ca n be i m ple me nt e d, e x ce pt f or c ha n ges necessar y t o eli mi nate a n 
i m me diate hazar d t o st u d y s u bjects, or w he n t he c ha n ge i n v ol ves o nl y l o gistical or a d mi nistrati ve 
as pects of t he tri al (e. g., c ha n ge i n m o nit or, c ha n ge of tele p h o ne n u m b er).  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 4  C O N DI TI O N S F O R T E R MI N A TI N G T H E S T U D Y   
Ka d m o n C or p orati o n has t he ri g ht t o ter mi nate t h e st u d y at a n y ti me .  I n t er mi nati n g t he st u d y, 
Ka d m o n C or p orati o n a n d t he I n v esti gat or will e ns ure t hat a de q u ate c o nsi d erati o n is gi ve n t o t he 
pr otecti o n of t he s u bjects ’ i nterests. 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 5  S T U D Y D O C U M E N T A TI O N , C R F S , A N D R E C O R D K E E PI N G   
1 5. 1  In vesti g at or’s Files a n d Rete nti o n of D oc u me nts   
T he I n vesti gat or m ust mai ntai n a de q uate a n d acc urate rec or ds t o e n a ble t h e c o n d uct of t he st u d y 
t o be f ull y d oc u m e nte d a n d t he st u dy data t o b e s u bse q ue ntl y v erifie d .  T hese d oc u me nts s h o ul d 
be classifie d i nt o 2  se parate cat e g ories:  I n vesti gat or’s S t u d y F iles a n d S u bject C li nical S o urce 
d oc u me nts.  
T he I n vesti gat or’s st u d y file will c o ntai n t he pr ot oc ol a n d pr ot oc ol a me n d m e nts, e C R Fs, q uer y 
f or ms, I R B/I E C, a n d g o v er n me ntal a p pr o val wit h c orres p o n d e nce, s a m ple I C F, dr u g rec or ds, 
staff c urric ul u m vitae, a ut h orizati o n f or ms, a n d ot her a p pr o priate d oc u m e nts a n d 
c orres p o n d e nce.  
S u bject cli nical s o urce d oc u me nts ( us uall y pre d efi ne d b y t he pr oject t o rec or d ke y efficac y a n d 
safet y para meters i n de pe n de nt of t he e C R Fs) ma y i ncl u de s u bject h os pital/cli nic rec or ds, 
p h ysicia n ’s a n d n urs e’s n otes, a p p oi nt me nt b o o k, ori gi nal la b orat or y re p orts, E C G, 
electr oe n ce p h al o gra m, X -ra y, pat h ol o g y a n d s pecial assess me nt re p orts, si g ne d I C Fs, c o ns ulta nt 
letters, a n d s u bject scree ni n g a n d e nr oll me nt l o gs .  T he I n vesti gat or m ust k ee p t hese d o c u me nts 
o n file f or at least 2  years f oll o wi n g t he mar keti n g a p plicati o n a p pr o val d ate f or t he st u d y dr u g 
a n d f or t he i n di cati o n bei n g i n vesti gate d or f or 2  years after t he i n v esti gati o n is disc o nti n ue d a n d 
t he F D A is n otifie d .  After t hat peri o d of ti me, t he d oc u me nts ma y b e destr o ye d s u bject t o l ocal 
re g ulati o ns wit h pri or writte n per missi o n fr o m Ka d m o n C or p orati o n .  If t he I n vesti gat or wa nts t o 
assi g n t he st u d y rec or ds t o a n ot her part y or m o ve t he m t o a n ot her l ocati o n, Ka d m o n C or p orati o n  
m ust be n otifie d i n a d va n ce.  
If t he I n vesti gat or ca n n ot g uara nte e t he arc hi vi n g re q uire me nt at t he st u d y site f or a n y or all of 
t he d oc u ments, s pecial arra n ge me nts m ust be ma d e bet wee n t he I n vesti gat or a n d Ka d m o n 
C or p orati o n  t o st ore t hes e i n a seale d c o ntai ner o utsi de of t he st u d y site s o t hat t he y ca n b e 
ret ur ne d seale d t o t he I n v esti gat or i n case of a re g ulat or y a u dit.  W he n s o urce d oc u me nts are 
re q uire d f or t he c o nti n ue d care of t he s u bject, a p pr o priate c o pi es s h o ul d be ma de f or st ori n g 
o utsi de of t he st u d y site.  
1 5. 2  S o urce D oc u me nts a n d B ac k gr o u n d D at a   
U p o n re q uest, t he I n vesti gat or will s u p pl y Ka d m o n C or p orati o n  wit h a n y re q uire d bac k gr o u n d 
data fr o m t he st u d y d oc u me ntati o n or cli nic rec or ds . I n case of s peci al pr o ble ms or g o v er n me ntal 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
q ueries or re q uests f or a u dit i ns pecti o ns, it is als o necessar y t o h a ve access t o t he c o m plete st u d y 
rec or ds, pr o vi de d t hat s u bject c o nfi de ntialit y is pr otecte d. 
1 5. 3  A u dits a n d I ns pecti o ns   
T he I n vesti gat or s h o ul d u n dersta n d t hat s o urce d oc u me nts f or t his st u d y s h o ul d be ma de 
a vaila ble t o a p pr o priatel y q ualifie d pers o n nel fr o m t he Ka d m o n C or p orati o n  Q ualit y Ass ura n ce 
U nit ( or desi g nee), or t o healt h a ut h orit y i ns p ect ors after a p pr o priate n otifi cati o n .  T he 
verificati o n of t he e C R F data m ust be b y direc t i ns pecti o n of s o urce d oc u me nts. 
1 5. 4  Electr o nic C ase Re p ort F or ms   
Cli nical trial data f or t his st u d y will be ca pt ure d o n e C R F s.  T he I n v esti gat or will a gree t o 
pr o vi de all i nf or mati o n re q ueste d o n t he e C R F i n a n acc urate m a n ner acc or di n g t o i nstr ucti o ns 
pr o vi de d.  Electr o nic C R Fs are desi g ne d f or c o m p uter pr ocessi n g a n d a nal ysis.  T he I n vesti gat or 
s h o ul d e ns ure t he acc urac y, c o m plete ness, a n d ti meli ness of t he data re p orte d t o Ka d m o n  
C or p orati o n  ( or desi g nee) i n t he e C R F a n d i n all r e q uire d re p orts. 
A n e C R F is re q uir e d t o be s u b mitte d f or e ver y s u bject w h o pr o vi des i nf or m e d c o nse nt.  T his 
i ncl u des s u b missi o n of retrie va ble data o n s u bj ects w h o wit h dra w bef ore c o m pleti o n of t he 
st u d y.  T he  e C R Fs m ust be re vie we d f or c o m plete ness a n d acc urac y, a n d el ectr o nicall y si g ne d 
w here  i n dicate d, b y t he Pri nci pal I n vesti gat or or a ut h orize d dele gate fr o m t he st u d y staff.  If a 
s u bject st o ps treat me nt or ter mi nates fr o m t he st u d y, t he dates a n d reaso ns m ust be n ote d o n t he 
e C R F. 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 6  M O NI T O RI N G O F T H E S T U D Y   
It is u n derst o o d t hat t he res p o nsi ble Ka d m o n C or p orati o n  m o nit or ( or desi g nee) will c o ntact a n d 
visit t he I n vesti gat or re g ularl y a n d will be all o we d o n re q uest t o i ns pect t h e vari o us rec or ds of 
t he trial (e C R Fs a n d ot her perti ne nt data) pr o vi de d t hat s u bject c o nfi de ntialit y is mai ntai ne d i n 
acc or da nce wit h l ocal re q uire me nts.  
It will be t he st u d y m o nit or ’s res p o nsi bilit y t o i ns p ect t he e C R Fs at re g ular i nter vals t hr o u g h o ut 
t he st u d y, t o v erif y t he a d here nce t o t he pr ot oc ol a n d t he c o m plete ness, c o nsiste nc y, a n d acc urac y 
of t he data bei n g e ntere d o n t he m .  T he st u d y m o nit or s h o ul d ha ve access t o la b orat or y test 
re p orts a n d ot her s u bject rec or ds n ee de d t o v erif y t he e ntries o n t he e C R F.  T he I n vesti gat or ( or 
desi g nee) m ust a gree t o c o o perate wit h t he m o nit or t o e ns ure t hat a n y pr o bl e ms detecte d i n t he 
c o urse of t hes e m o nit ori n g visits are res ol ve d.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 7  C O N FI D E N TI A LI T Y O F T RI A L D O C U M E N T S A N D S U B J E C T R E C O R D S   
T he I n vesti gat or m ust e ns ure t hat s u bjects ’ a n o n y mit y will be mai ntai ne d a n d t hat t heir i de ntities 
are pr ot ecte d fr o m u na ut h orize d parties .  O n e C R Fs or ot her d oc u me nts s u b mitte d t o Ka d m o n 
C or p orati o n , s u bjects s h o ul d be i de ntifie d b y a n i d e ntificati o n c o de a n d n ot b y t heir n a mes.  T he 
s u bjects’ pers o nal i nf or m ati o n s h o ul d be re dacte d o n all s o urce d oc u m e nts pri or t o s u b missi o n t o 
Ka d m o n C or p orati o n  (or desi g nee) .  T h e I n v esti gat or s h o ul d kee p a s u bject e nr oll me nt l o g 
s h o wi n g c o d es, na mes, a n d a d dresses.  T he I n v esti gat or s h o ul d mai ntai n d oc u me nts n ot f or 
s u b missi o n t o Ka d m o n C or p orati o n  (e.g ., s u bjects’ writte n c o nse nt f or ms) i n strict c o nfi de nce.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 8  P U B LI C A TI O N O F D A T A A N D P R O T E C TI O N O F T R A D E S E C R E T S   
T he res ults of t his st u d y ma y b e p u blis he d or pres e nte d at scie ntific meeti n gs .  T h e I n vesti gat or 
a grees t o s u b mit all ma n uscri pts or a bstracts t o Ka d m o n C or p orati o n  f or re vie w at least 3 0 da ys 
bef ore s u b missi o n .  T his all o ws Ka d m o n C or p orati o n  t o pr otect pr o prietar y i nf or mati o n a n d t o 
pr o vi de c o m me nts base d o n i nf or mati o n fr o m ot her st u dies t hat ma y n ot yet be a vaila ble t o t he 
I n v esti gat or. 
I n t he e ve nt t hat K a d m o n C or p orati o n  c o or di nates a p u blicati o n or pres e ntati o n of st u d y res ults 
fr o m all st u d y sites, t he p artici pati o n of I n vesti gat or or ot her re pres e ntati ves of st u d y site as a 
na me d a ut h or s hall be d eter mi ne d i n acc or da nce  wit h Ka d m o n C or p orati o n  p olic y a n d ge nerall y 
acce pte d sta n dar ds f or a ut h ors hi p.  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 6 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 9  R E F E R E N C E S   
1.  Lee SJ.  Classificati o n s yste ms f or c hr o nic graft -vers us -h ost disease.  Bl o o d. 2 0 1 7; 1 2 9( 1): 3 0 -3 7  
2.  Arai S, Ar ora M, Wa n g T, et al. I ncreasi n g i nci de nce of c hr o nic graft -vers us -h ost disease i n 
all o ge neic tra ns pla ntati o n: a re p ort fr o m t he Ce nter f or I nter nati o nal Bl o o d a n d Marr o w Tra ns pla nt 
Researc h. Bi ol Bl o o d Marr o w Tra ns pla nt. 2 0 1 5; 2 1( 2) : 2 6 6-2 7 4  
3.  Ar ora M, C utler C S, Ja gasia M H, et al. Late ac ute a n d c hr o nic graft -vers us -h ost disease after 
all o ge neic he mat o p oietic cell tra ns pla ntati o n. Bi ol Bl o o d Marr o w Tra ns pla nt. 2 0 1 6; 2 2( 3): 4 4 9 -4 5 5.  
4.  Fl o wers M E, Marti n PJ.  H o w we treat c hr o nic graft -vers u s-h ost disease.  Bl o o d. 2 0 1 5; 1 2 5( 4): 
6 0 6 -6 1 5  
5.  Gar nett C et al. Treat me nt a n d ma na ge me nt of graft -vers us -h ost disease: i m pr o vi n g res p o nse a n d 
s ur vi val. T her A d v He mat ol. 2 0 1 3; 4 6( 6): 3 6 6 -3 7 8  
6.  Rez ur oc k ( Bel u m os u dil) Prescri bi n g I nf or mati o n 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 2 1/ 2 1 4 7 8 3s 0 0 0l bl. p df   Accesse d 
2 2  J ul 2 0 2 1  
7.  I br uti ni b Prescri bi n g I nf or mati o n 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/la bel/ 2 0 1 7/ 2 0 5 5 5 2s 0 2 0l bl. p df  accesse d 
2 8  Mar  2 0 1 8   
8.  It o h, K et al. A n esse ntial part f or R h o -ass ociate d ki nas e i n t he tra nscell ular i n vasi o n of t u m or cells. 
Nat ure M e d. 1 9 9 9;5 , 2 2 1-2 2 5 . d oi: 1 0. 1 0 3 8/ 5 5 8 7.  
9.  Ols o n, M F , Sa hai, E. T he acti n c yt os kelet o n i n ca ncer cell m otilit y. Cli n E x p Metastasis . 
2 0 0 9; 2 6 :2 7 3 -2 8 7 . d oi: 1 0. 1 0 0 7/s 1 0 5 8 5 -0 0 8 -9 1 7 4 -2.  
1 0.  Rie nt o K , Ri dle y AJ.  R oc ks: m ultif u ncti o nal ki nases i n cell be ha vi o ur. Nat Re v M ol Cell Bi ol . 
2 0 0 3; 4, 4 4 6 -4 5 6 . d oi: 1 0. 1 0 3 8/ nr m 1 1 2 8.  
1 1.  Sc h ofiel d A V , Ber nar d O. R h o -ass ociate d c oile d -c oil ki nase ( R O C K) si g nali n g a n d disease. Crit Re v 
Bi oc he m M ol Bi ol . 2 0 1 3; 4 8 : 3 0 1 -3 1 6, d oi: 1 0. 3 1 0 9/ 1 0 4 0 9 2 3 8. 2 0 1 3. 7 8 6 6 7 1.  
1 2.  Li Y. et al. P h os p h or ylate d E R M is res p o nsi ble f or i ncrease d T cell p olarizati o n, a d hesi o n, a n d 
mi grati o n i n patie nts wit h s yste mic l u p us er yt he mat os us. J o ur nal of Im m u n . 2 0 0 7;1 7 8, 1 9 3 8 -1 9 4 7.  
1 3.  T y b ule wicz V L , He n ders o n R B. R h o fa mil y G T Pases a n d t heir re g ulat ors i n l y m p h oc ytes. Nat Re v 
I m m u n ol. 2 0 0 9;9 : 6 3 0 -6 4 4, d oi: 1 0. 1 0 3 8/ nri 2 6 0 6.  
1 4.  R oz o C et al. Tar geti n g t he R h o A -R O C K pat h wa y t o re verse T -cell d ysf u ncti o n i n S L E. A n n R he u m 
Dis . 2 0 1 6;7 6 : 7 4 0 -7 4 7 . d oi: 1 0. 1 1 3 6/a n nr he u m dis -2 0 1 6 -2 0 9 8 5 0.  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
1 5.  Bi s was P S et al. P h os p h or ylati o n of I R F 4 b y R O C K 2 re g ulates I L -1 7 a n d I L -2 1 pr o d ucti o n a n d t he 
de vel o p me nt of a ut oi m m u nit y i n mice. J Cli n I n vest. 2 0 1 0;1 2 0 :3 2 8 0 -3 2 9 5 . d oi: 1 0. 1 1 7 2/J CI 4 2 8 5 6.  
1 6.  He Y et al. A ntii nfla m mat or y effect of R h o ki nase bl oc ka de via i n hi biti o n of N F-ka p pa B acti vati o n i n 
r he u mat oi d art hritis. Art hritis R he u m . 2 0 0 8;5 8 : 3 3 6 6 -3 3 7 6 . d oi: 1 0. 1 0 0 2/art. 2 3 9 8 6.  
1 7.  Is gr o J et al. E n ha nce d r h o-ass ociate d pr otei n ki nase acti vati o n i n patie nts wit h s yste mic l u p us 
er yt he mat os us. Art hritis R he u m . 2 0 1 3;6 5 :1 5 9 2 -1 6 0 2 . d oi: 1 0. 1 0 0 2/art. 3 7 9 3 4.  
1 8.  Za ni n -Z h or o v A et al. Selecti ve oral R O C K 2 i n hi bit or d o w n -re g ulates I L-2 1 a n d I L -1 7 secreti o n i n 
h u ma n T cells via S T A T 3 -de pe n de nt mec ha nis m. Pr oc Natl Aca d Sci U S A . 2 0 1 4;1 1 1 :1 6 8 1 4 -1 6 8 1 9 . 
d oi: 1 0. 1 0 7 3/ p nas. 1 4 1 4 1 8 9 1 1 1.  
1 9.  Lee SJ et al. Se verit y of c hr o nic graft -vers us -h ost disease: ass ociati o n wit h treat me nt -relate d 
m ortalit y a n d rela pse. Bl o o d . 2 0 0 2;1 0 0 :4 0 6 -4 1 4.  
2 0.  Mac D o nal d K P, Blazar B R , Hill G R. C yt o ki ne me diat ors of c hr o nic graft-vers us -h ost disease. J  Cli n 
I n vest. 2 0 1 7;1 2 7, 2 4 5 2 -2 4 6 3 . d oi: 1 0. 1 1 7 2/J CI 9 0 5 9 3.  
2 1.  Ba n o vic T et al. T G F -beta i n all o ge neic ste m cell tra ns pla ntati o n: frie n d or f oe? Bl o o d . 
2 0 0 5; 1 0 6 :2 2 0 6 -2 2 1 4 . d oi: 1 0. 1 1 8 2/ bl o o d -2 0 0 5 -0 1 -0 0 6 2.  
2 2.  Sri ni vasa n M et al. D o n or B -cell all oa nti b o d y de p ositi o n a n d ger mi nal ce nter f or ma ti o n are re q uire d 
f or t he de vel o p me nt of m uri ne c hr o nic G V H D a n d br o nc hi olitis o blitera ns. Bl o o d. 
2 0 1 2; 1 1 9 :1 5 7 0 -1 5 8 0 . d oi: 1 0. 1 1 8 2/ bl o o d -2 0 1 1 -0 7 -3 6 4 4 1 4.  
2 3.  Ra d oj cic V et al. S T A T 3 si g nali n g i n C D 4 + T cells is critical f or t he pat h o ge nesis of c hr o nic 
scler o der mat o us graft -vers us -h ost disease i n a m uri ne m o del. J Im m u n ol  2 0 1 0; 1 8 4 :7 6 4 -7 7 4 . 
d oi: 1 0. 4 0 4 9/ji m m u n ol. 0 9 0 3 0 0 6.  
2 4.  Fl y n n R et al. T ar gete d R h o -ass ociate d ki nase 2 ( R O C K 2) i n hi biti o n decreases cli nical a n d i m m u ne 
pat h ol o g y of m uri ne a n d h u ma n c hr o nic G V H D t hr o u g h  Stat 3 -de pe n de nt mec ha nis m. Bl o o d . 2 0 1 6, 
d oi: 1 0. 1 1 8 2/ bl o o d -2 0 1 5 -1 0 -6 7 8 7 0 6 ( 2 0 1 6).  
2 5.  Lee SJ, W olff D, Kit k o C, et al. Meas uri n g T hera pe utic Res p o nse i n C hr o nic Graft -vers us -H ost 
Disease. Nati o nal I nstit utes of Healt h C o nse ns us De vel o p me nt Pr oject o n Criteria f or Cli nical Trials 
i n C hr o nic Graft-vers us -H ost Disease: I V. T he 2 0 1 4 Res p o nse Criteria W or ki n g Gr o u p Re p ort. Bi ol 
Bl o o d Marr o w Tra ns pla nt. 2 0 1 5; 2 1: 9 8 4 – 9 9 9.  
2 6.  Ja gasia M H et al, Nati o nal I nstit utes of Healt h C o nse ns us De vel o p me nt Pr oject o n Criteria f or 
Cli n ical Trials i n C hr o nic Graft-vers us -H ost Disease: I. T he 2 0 1 4 Dia g n osis a n d Sta gi n g W or ki n g 
Gr o u p re p ort. Bi ol Bl o o d Marr o w Tra ns pla nt. 2 0 1 5; 2 1: 3 8 9 – 4 0 1 . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
2 7.  Lee S, C o o k E F, S oiffer R et al. De vel o p me nt a n d vali dati o n of a scale t o meas ure s y m pt o ms of 
c hr o nic graft-vers us -h ost disease. Bi ol Bl o o d Marr o w Tra ns pla nt . 2 0 0 2; 8: 4 4 4-4 5 2.  
2 8.  Kar n ofs k y D A, B urc he nal J H. 1 9 4 9. T he Cli nical E val uati o n of C he m ot hera pe utic A ge nts i n Ca ncer. 
I n E val uati o n of C he m ot hera pe utic A ge nts: S y m p osi u m Hel d at t he Ne w Y or k Aca de m y of 
Me d ici ne, Mac Le o, e d. ( Ne w Y or k, C ol u m bia U ni versit y Press), p. 1 9 1-2 0 5.  
2 9.  Le ve y A S, C ores h J, Gree ne T, Ste ve ns L A, Z ha n g Y L, He n dri kse n S, K use k J W, va n Le nte F, 
C hr o nic Ki d ne y Disease E pi de mi ol o g y C olla b orati o n. Usi n g sta n dar dize d ser u m creati ni ne val ues i n 
t he m o dificati o n of diet i n re nal disease st u d y e q uati o n f or esti mati n g gl o mer ular filtrati o n rate. A n n 
I nter n Me d. 2 0 0 6 A u g 1 5; 1 4 5( 4): 2 4 7-5 4.  
3 0.  C o bert B 2 0 1 2. C o bert’s Ma n ual of Dr u g Safet y a n d P har mac o vi gila nce ( 2 n d e d.) Massac h usetts: 
J o nes a n d Barlett Lear ni n g, L L C.  
3 1.  F D A. Dr u g De vel o p me nt a n d Dr u g I nteracti o ns, T a ble of S u bstrates, I n hi bit ors a n d I n d ucers 
htt ps:// w w w.f da. g o v/ dr u gs/ de vel o p me nta p pr o val pr ocess/ de vel o p me ntres o urces/ dr u gi nteracti o nsla beli
n g/ uc m 0 9 3 6 6 4. ht m .  Accesse d 2 5 J u n 2 0 21.  
3 2.  Cre di ble Me ds  2 0 2 0: htt ps://cre di ble me ds. or g/ p dft e m p/ p df/ C o m bi ne d List. p df   Accesse d 
1 1  Ma y  2 0 2 0 . 
3 3.  Li u D, A h met A, War d L, Kris h na m o ort h y P, Ma n delc or n E D, Lei g h R, Br o w n JP, C o he n A, Ki m H. 
A practical g ui de t o t he m o nit ori n g a n d ma na ge me nt of t he c o m plicati o ns of s yste mic c ortic oster oi d 
t hera p y. Aller g y Ast h ma Cli n I m m u n ol. 2 0 1 3 A u g; 9( 1): 3 0.  
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  A: Sc he d ule of Assess me nts   
Ta ble 7 . 
Sc he d ule of Assess me nts  
Assess me nt  
Tre at me nt Peri o d  
F oll o w -U p Peri o d  
Assess me nt  
B aseli ne a 
M o nt h 3 a n d  
E ver y 3 M o nt hs T here after  
2 8 -d a y F oll o w -u p Visit  
 (2 8 D a ys fr o m L ast D ose)  
Wi n d o w  
 
± 1 4 d a ys  
± 7 d a ys  
E val uate I/ E Criteria  
X  
 
 
Si g n I C F  
X  
 
 
St u d y K D 0 2 5 -2 0 8 or 
St u d y  K D 0 2 5 -2 1 3 Hist or y b 
X  
 
 
E F FI C A C Y A S S E S S M E N T S  
Cli nicia n -re p orte d Gl o bal 
c G V H D Acti vit y 
Assess me nt  
X  
X  
 
Res p o nse Assess me nt   
X  
X  
 
P F T c 
X  
X  
 
L S S  
X  
X  
 
D oc u me nt C ortic oster oi d 
D osa ge  
Data t o be c ollecte d fr o m t he date t he I C F is si g ne d u ntil 2 8 da ys after t he last d ose 
of st u d y dr u g  
D oc u me nt Ot her c G V H D 
T hera pies  
Data t o be c ollecte d fr o m t he date t he I C F is si g ne d u ntil 2 8 da ys after t he last d ose 
of st u d y dr u g  
S A F E T Y A S S E S S M E N T S  
S y m pt o m -directe d P E  
X  
X  
X  
Vital Si g ns d 
X  
X  
X  
W ei g ht  
X  
X  
X  
Hei g ht  
X  
 
 
K P S  
X  
X  
X  
He mat ol o g y  
X  
X  
X  
Cli nical C he mistr y  
X  
X  
X  
1 2 -lea d E C G 
X  
X  
X  
Pre g na nc y T est ( Uri ne) e 
X  
X  
X  
C o nc o mita nt Me dicati o ns 
a n d Pr oce d ures  
Data t o be c ollecte d fr o m t he date t he I C F is si g ne d u ntil 2 8 da ys after t he last d ose 
of st u d y dr u g  
A Es  
A Es t o be c ollecte d fr o m t he date t he I C F is si g ne d u ntil 2 8 da ys after t he last d ose 
of st u d y dr u g  
B E L U M O S U DI L  
St u d y Dr u g A d mi nistrati o n f 
X  
X  
 
Dis pe nse St u d y Dr u g Diar y  
X  
X  
 
C ollect St u d y Dr u g Diar y  
 
X  
X  
A E = a d verse e ve nt; BI D = t wice dail y; c G V H D = c hr o nic graft -vers us -h ost disease; D L C O = diff use ca pacit y of car b o n 
m o n o xi d e;  E C G = electr o car di o gra p h; F E V 1 = f orce d e x pirat or y v ol u me i n 1 sec o n d; F V C = f orce d vital ca pacit y; H b = 
he m o gl o bi n; I C F = i nf or me d c o nse nt f or m; I/ E = i n cl usi o n/e xcl usi o n criteria; K P S = Kar n ofs k y P erfor ma nce Stat us; L S S = Lee 
S y m pt o m Scale sc ore; L T F U = l o n g -ter m f oll o w-u p; P E = p h ysical e xa mi n ati o n; P F T = p ul m o nar y f u ncti o n test ; Q D = o nce 
dail y; R V = resi d ual v ol u me; T L C = t otal l u n g ca pacit y  
a. E val u ati o n of i n cl usi o n/e xcl usi o n criteria a n d si g ni n g of I C F d o n ot necessaril y ha ve t o occ ur o n t he sa me da y as efficac y a n d 
safet y assess me nts.  H o we ver, t h e I C F m ust b e si g ne d bef ore a n y st u d y pr oce d ures b e gi n.  
b. At Baseli ne, t h e f oll o wi n g assess me nts n ee d t o be d oc u me nte d fr o m t h e K D 0 2 5 -2 0 8 or K D 0 2 5 -2 1 3 st u dies: d osi n g gr o u p t o 
w hic h t h e s u bject was assi g ne d or ra n d o mize d, Cli nicia n -re p orte d Gl o bal c G V H D Acti vit y Assess m e nt fr o m C ycle 1 Da y 1, a n d 
o n g oi n g A E s. 
c. P ul m o nar y f u ncti o n tests are t o be c o n d ucte d f or s u bjects wit h l u n g c G V H D or w he n c G V H D is s us pecte d a n d i n cl u de: F E V 1, 
F V C, D L C O  (c orrecte d f or H b), R V, a n d T L C . 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
d . Vital si g n meas ure me nts i ncl u de sitti n g bl o o d press ure a n d heart rate (aft er 5 mi n utes of rest); res pirat or y rate; a n d 
te m per at ure.  
e. Fe mal es of c hil d beari n g p ote ntial m ust h a ve a ne gati ve uri n e pre g na nc y test.  P ositi ve res ults are t o be c o nfir me d wit h ser u m 
testi n g. 
f. S u bjects will recei ve t h e sa me d ose of bel u m os u dil as t h e y were assi g ne d a n d recei ve d d uri n g St u d y K D 0 2 5-2 0 8 or 
St u d y  K D 0 2 5 -2 1 3 ( i.e., bel u m os u dil 2 0 0 m g Q D, 2 0 0 m g BI D, or 4 0 0 m g Q D).  First d ose ma y be ta ke n at h o me or i n t h e cli nic.  
 
N ote:  F oll o wi n g t h e 2 8 -da y F oll o w -u p Visit, s u bjects will ha ve L T F U b y bei n g c o ntacte d b y tele p h o ne, e -mail, or p ostal mail t o 
c o nfir m s ur vi val stat us, a n y i nitiati o n of ne w s yste mic c G V H D t h era pies, a n d rela pse of u n derl yi n g disease.   If t h e s u bject was i n 
L T F U i n St u d y K D 0 2 5 -2 0 8 or i n St u d y  K D 0 2 5 -2 1 3, t h e s u bject will o nl y ha ve L T F U assess me nts p erf or me d o nce 
a p pr o xi matel y e ver y 3 m o nt hs  (Secti o n 6. 2. 5 ).   
 
N ote:  At U nsc he d ule d Visit, s u bject s h o ul d n ot recei ve ha ve a n y re mai ni n g  bel u m os u dil c ollecte d, or ha ve st u d y diaries 
dis pe nse d or c ollecte d u nless treat me nt is st o p pe d.  
 
N ote:  T he assess me nts a n d pr oce d ures p erf or me d at a n y u nsc he d ule d visit de pe n d o n t h e cli nical j u d g me nt of t h e I n vesti gat or.  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  B: Cli nici a n -re p orte d Gl o b al c G V H D Acti vit y Assess me nt   
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
E S O P H A G U S  
N o es o p h a g e al 
s y m pt o ms 
Occ asi o n al d ys p h a gi a or 
o d y n o p h a gi a wit h s oli d 
f o o d or pills d uri n g t h e 
p ast w e ek  
I nt er mitt e nt d ys p h a gi a 
or o d y n o p h a gi a wit h 
s oli d f o o ds or pills, b ut 
n ot f or li q ui ds or s oft 
f o o ds, d uri n g t h e p ast 
w e ek  
Dys p h a gi a or 
o d y n o p h a gi a f or al m ost 
all or al i nt a k e, o n 
al m ost ev ery d a y of t h e 
p ast w e ek  
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
U P P E R GI  
N o sy m pt o ms  
Mil d, occ asi o n al 
s y m pt o ms, wit h littl e 
r e d ucti o n i n or al i nt a k e 
d uri n g t h e p ast w e ek  
M o d er at e, i nt er mitt e nt 
s y m pt o ms, wit h s o m e 
r e d ucti o n i n or al i nt a k e 
d uri n g t h e p ast w e ek  
M or e s ev er e or 
p ersist e nt sy m pt o ms 
t hr o u g h o ut t h e d a y, 
wit h m ark e d r e d ucti o n 
i n oral i nt a k e, o n al m ost 
ev ery d a y of t h e p ast 
w e ek  
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E  3  
 
 
L O W E R GI 
N o l o os e or li q ui d st o ols 
d uri n g t h e p ast w e ek  
Occ asi o n al l o os e or 
li q ui d st o ols, o n s o m e 
d ays d uri n g t h e p ast 
w e ek  
I nt er mitt e nt l o os e or 
li q ui d st o ols t hr o u g h o ut 
t h e d a y, o n al m ost 
ev ery d a y of t h e p ast 
w e ek , wit h o ut 
r e q uiri n g i nt erv e nti o n 
t o pr ev e nt or c orr ect 
v ol u m e d e pl eti o n  
V ol u mi n o us di arr h e a  
a o n al m ost ev ery d a y 
of t h e p ast w e ek, 
r e q uiri n g i nt erv e nti o n 
t o pr ev e nt or c orr ect 
v ol u m e d e pl eti o n  
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
L U N G S 
N o sy m pt o ms  
Mil d s y m pt o ms 
(s h ort n ess of br e at h 
aft er cli m bi n g o n e fli g ht 
of st e ps)  
M o d er at e sy m pt o ms 
(s h ort n ess of br e at h 
aft er w alki n g o n fl at 
gr o u n d)  
S ev er e sy m pt o ms 
(s h ort n ess of br e at h at 
r est; r e q uiri n g O2) 
 
 
□ 
□ 
□ 
□ 
 
 
 
S pir o m etr y  
N ot d o n e □ 
 
F E V 1  
( % Pr e dict e d): 
 
_ _ _ _ _ _  
F E V 1  
(L): 
 
_ _ _ _ _ _  
F V C  
( % Pr e dict e d): 
 
_ _ _ _ _ _  
F V C 
(L): 
 
_ _ _ _ _ _  
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
E Y E S  
N o sy m pt o ms  
Mil d dry e y e sy m pt o ms n ot 
aff ecti n g A DL (r e q uir e m e nt of 
l u bric a nt ey e dr o ps ≤ 3 x p er 
d ay)  
M o d er at e dr y ey e sy m pt o ms 
p arti all y aff ecti n g A DL 
(r e q uiri n g l u bric a nt ey e 
dr o ps > 3 x p er d a y or 
p u nct al pl u gs).  
WI T H O U T  n e w visi o n 
i m p air m e nt d u e t o K C S 
S ev er e dry ey e 
s y m pt o ms 
si g nific a ntly 
aff ecti n g A DL 
(s p eci al e y e w e ar 
t o r eli ev e p ai n) 
O R  u n a bl e t o 
w ork b ec a us e of 
oc ul ar 
s y m pt o ms O R 
l oss of visi o n d u e 
t o K C S 
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify): 
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
S C O R E 0  
S C O R E 1  
S C O R E 2  
S C O R E 3  
 
 
J OI N T S 
A N D 
F A S CI A  
N o sy m pt o ms  
Mil d ti g ht n ess of ar ms or 
l e gs, n or m al or mil d 
d ecr e as e d r a n g e of m oti o n 
( R O M) A N D n ot aff ecti n g A DL 
Ti g ht n ess of ar ms or l e gs O R 
j oi nt c o ntr act ur es, eryt h e m a 
t h o u g ht d u e t o f asciitis, 
m o d er at e d ecr e as e R O M 
A N D mil d t o m o d er at e 
li mit ati o n of A DL 
C o ntr act ur es 
WI T H si g nific a nt 
d ecr e as e of 
R O M A N D 
si g nific a nt 
li mit ati o n of A DL 
( u n a bl e t o ti e 
s h o es, b utt o n 
s hirts, dr ess s elf 
etc.)  
 
 
□ 
□ 
□ 
□ 
 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
P -R O M 
Sc or e 
 
 
 
Sc or e    _ _ _ _ _  
N ot d o n e   □ 
 
 
Sc or e    _ _ _ _ _  
N ot d o n e   □ 
 
Sc or e    _ _ _ _ _  
N ot d o n e   □ 
 
Sc or e    _ _ _ _ _  
N ot d o n e   □ 
 □ A b n or m ality pr es e nt b ut ex pl ai n e d e ntir ely b y n o n -G V H D d oc u m e nt e d c a us e (s p ecify):  
  
 □ A b n or m ality t h o u g ht t o r e pr es e nt G V H D PL U S ot h er c a us es (s p ecify):  
  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
 
 
S o urces:  Lee et al . 2 0 1 5(2 5 ) a n d Ja gasia et al. 2 0 1 5 (2 6 ) 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 8  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  C : cG V H D Res p o nse Assess me nt   
 
S o urce:  Lee et al. 2 0 1 5 (2 5 )   
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 7 9  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  D: Lee c G V H D S y m pt o m Sc ore   
B y circli n g o ne n u m ber per li ne, please i n dicate h o w m uc h y o u ha ve bee n b ot here d b y t he f oll o wi n g 
pr o ble ms i n t he past 7 da ys: ( Lee et al. 2 0 0 2(2 7 )) 
S ki n  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
1.  
A b n or mal s ki n c ol or  
0  
1  
2  
3  
4  
2.  
Ras hes  
0  
1  
2  
3  
4  
3.  
T hic ke ne d s ki n  
0  
1  
2  
3  
4  
4.  
S ores o n s ki n  
0  
1  
2  
3  
4  
5.  
Itc h y s ki n 
0  
1  
2  
3  
4  
E yes a n d M o ut h  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
6.  
Dr y e yes  
0  
1  
2  
3  
4  
7.  
Nee d t o use e ye dr o ps fre q ue ntl y  
0  
1  
2  
3  
4  
8.  
Diffic ult y seei n g clearl y  
0  
1  
2  
3  
4  
9.  
Nee d t o a v oi d certai n f o o ds d ue t o 
m o ut h pai n  
0  
1  
2  
3  
4  
1 0.  
Ulcers i n m o ut h  
0  
1  
2  
3  
4  
1 1.  
Recei vi n g n utriti o n fr o m a n d 
i ntra ve n o us li ne or fee di n g t u be 
0  
1  
2  
3  
4  
Bre at hi n g  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
1 2.  
Fr e q ue nt c o u g h  
0  
1  
2  
3  
4  
1 3.  
C ol ore d s p ut u m  
0  
1  
2  
3  
4  
1 4.  
S h ort ness of breat h wit h e xercise  
0  
1  
2  
3  
4  
1 5.  
S h ort ness of breat h at rest  
0  
1  
2  
3  
4  
1 6.  
Nee d t o use o x y ge n  
0  
1  
2  
3  
4  
E ati n g a n d Di gesti o n  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
1 7.  
Diffic ult y s wall o wi n g s oli d f o o ds  
0  
1  
2  
3  
4  
1 8.  
Diffic ult y s wall o wi n g li q ui ds  
0  
1  
2  
3  
4  
1 9.  
V o miti n g  
0  
1  
2  
3  
4  
2 0.  
Wei g ht l oss  
0  
1  
2  
3  
4  
M uscl es a n d J oi nts  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
2 1.  
J oi nt a n d m uscle ac hes 
0  
1  
2  
3  
4  
2 2.  
Li mite d j oi nt m o ve me nt  
0  
1  
2  
3  
4  
2 3.  
M uscle cra m ps  
0  
1  
2  
3  
4  
2 4.  
Wea k m uscle d  
0  
1  
2  
3  
4  
E ner g y  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
2 5.  
L oss of e ner g y  
0  
1  
2  
3  
4  
2 6.  
Nee d t o slee p m ore/ta ke na ps  
0  
1  
2  
3  
4  
2 7.  
Fe vers  
0  
1  
2  
3  
4  
Me nt al a n d E m oti o n al  
N ot at all  
Sli g htl y  
M o der atel y  
Q uite a bit  
E xtre mel y  
2 8.  
De pressi o n  
0  
1  
2  
3  
4  
2 9.  
A n xiet y  
0  
1  
2  
3  
4  
3 0.  
Diffic ult y slee pi n g  
0  
1  
2  
3  
4  
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 0  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  E : K ar n ofs k y Perf or m a nce Sc ale   
Sc ore  
Descri pti o n  
1 0 0  
N or mal, n o c o m plai nts, n o e vi de nce of disease  
9 0  
A ble t o carr y o n n or mal acti vit y  
8 0  
N or mal acti vit y wit h eff ort  
7 0  
Cares f or self; u na ble t o carr y o n n or mal acti vit y or t o d o acti ve w or k  
6 0  
Re q uires occasi o nal assista nce b ut is a ble t o care f or m ost nee ds  
5 0  
Re q uires c o nsi dera ble assista nce a n d fre q ue nt me dical care  
4 0  
Disa ble d; re q uires s pecial care  a n d assista nce 
3 0  
Se verel y disa ble d; h os pitalizati o n i n dicate d; deat h n ot i m mi ne nt  
2 0  
Ver y sic k; h os pitalizati o n i n dicate d; deat h n ot i m mi ne nt  
1 0  
M ori b u n d; fatal pr ocesses pr o gressi n g ra pi dl y  
Sc ores 8 0 t o 1 0 0: a ble t o carr y o n n or mal acti vit y; n o s pecial care is n ee de d 
Sc ores 5 0 t o 7 0: u na ble t o w or k; a ble t o li ve at h o me a n d care f or m ost p ers o nal nee ds; a var yi n g de gree of assista nce nee de d  
Sc ores 1 0 t o 4 0: u na ble t o care f or self; re q uires e q ui vale nt of i nstit uti o nal or h os pice care; disease ma y  be pr o gressi n g ra pi dl y  
S o urce:  Kar n ofs k y et al. 1 9 4 9 (2 8 ) 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 1  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  F : E q u ati o ns t o Pre dict Gl o mer ul ar Filtr ati o n R ate ( M D R D-4)   
4 -V ari a ble M o dific ati o n of Diet i n Re n al Dise ase ( M D R D -4) E q u ati o n  
Hi g h Le vel F or m ul a f or Bl ac k or Af ric a n -A meric a n M ales:  
Esti mate d G F R = 1 7 5 × ( Creati ni ne -1. 1 5 4) × ( A ge -0. 2 0 3) × 1. 2 1 2 
 
Hi g h Le vel F or m ul a f or M ales N O T Bl ac k or Af ric a n -A meric a n ( a n y ot her o pti o n):  
Esti mate d G F R = 1 7 5 × ( Creati ni ne -1. 1 5 4) × ( A ge -0. 2 0 3) 
 
Hi g h Le vel F or m ul a f or Bl ac k or Af ric a n -A meric a n F e m ales:  
Esti mate d G F R = 1 7 5 × ( Creati ni ne -1. 1 5 4) × ( A ge -0. 2 0 3) × 1. 2 1 2 × 0. 7 4 2 
 
Hi g h Le vel F or m ul a f or Fe m ales N O T Bl ac k or Afric a n -A meric a n ( a n y ot her o pti o n):  
Esti mate d G F R = 1 7 5 × ( Creati ni ne -1. 1 5 4) × ( A ge -0. 2 0 3) × 0. 7 4 2 
Le ve y et al. 2 0 0 6 (2 9 ) 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 2  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  G : Deter mi ni n g Rel ati o ns hi p of  A Es t o St u d y Dr u g   
1  
N O T R E L A T E D  
T his cate g or y a p plies t o t h ose A E s w hic h, after caref ul me dical c o nsi derati o n, are clearl y felt t o be d ue t o 
ex tra ne o us ca uses (e. g., disease, e n vir o n me nt, etc.) that are u nrelate d  t o t he a d mi nistrati o n of st u d y dr u g. 
2  
U N LI K E L Y R E L A T E D  ( m ust ha ve first 2) 
T his cate g or y a p plies t o t h ose A E s w hic h, after caref ul me dical c o nsi derati o n, are felt u nli kel y t o be 
relate d t o t he a d mi nistrati o n of t he st u d y dr u g.  T he relati o ns hi p of a n A E  t o t he st u d y dr u g ca n be 
c o nsi dere d u nli kel y  if: 
•  
It d oes n ot f oll o w a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he dr u g. 
•  
It c o ul d rea dil y ha ve bee n a res ult of t he s u bject’s cli nical state, e n vir o n me ntal or t ox ic fact ors, or 
ot her m o des of t hera p y a d mi nistere d t o t he s u bj ect.  
•  
It d oes n ot f oll o w a k n o w n res p o nse patter n t o t he s us pecte d dr u g. 
•  
It d oes n ot rea p pear or w orse n w he n t he dr u g is re-a d mi nistere d. 
3  
P O S SI B L Y R E L A T E D ( m ust ha ve first 2) 
T his cate g or y a p plies t o t h ose A E s w hic h, after caref ul me dical c o nsi derati o n, are felt u nli kel y t o be 
relate d t o t he a d mi nistrati o n of t he st u d y dr u g, b ut t he p ossi bilit y ca n n ot be r ule d o ut wit h certai nt y.  T he 
relati o ns hi p of a n A E  t o t he st u d y dr u g ca n be c o nsi dere d p ossi ble  if: 
•  
It f oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he dr u g. 
•  
It c o ul d rea dil y ha ve bee n a res ult of t he s u bject’s cli nical state, e n vir o n me ntal or t ox ic fact ors, or 
ot her m o des of t hera p y a d mi nistere d t o t he s u bj ect.  
•  
It f oll o ws a k n o w n res p o nse patter n t o t he s us pecte d dr u g. 
4  
P R O B A B L Y R E L A T E D ( m ust ha ve first 3) 
T his cate g or y a p plies t o t h ose A E s w hic h, after caref ul me dical c o nsi derati o n, are felt wit h a hi g h de gree 
of certai nt y t o be relate d t o t he a d mi nistrati o n of t he st u d y dr u g.  T he relati o n s hi p of a n A E  t o t he st u d y 
dr u g ca n be c o nsi dere d pr o ba ble  if: 
•  
It f oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he dr u g.  
•  
It c o ul d n ot be reas o na bl y ex plai ne d b y t he k n o w n c haracteristics of t he s u bject’s cli nical state, 
e n vir o n me ntal or t o x ic fact ors or ot her m o des of t hera p y a d mi nistere d t o t he s u bject.  
•  
It disa p pears or decreases u p o n cessati o n of dr u g or re d ucti o n i n d ose. * 
•  
It f oll o ws a k n o w n res p o nse patter n t o t he s us pecte d dr u g. 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 3  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
5  
D E FI NI T E L Y R E L A T E D ( m ust ha ve first 3) 
T his cate g or y a p plies t o t h ose A E s, w hic h, after caref ul me dical c o nsi derati o n, are felt t o be relate d t o t he 
a d mi nistrati o n of t he st u d y dr u g.  T he relati o ns hi p of a n A E  t o t he st u d y dr u g ca n be c o nsi dere d relate d if: 
•  
It f oll o ws a reas o na ble te m p oral se q ue nce fr o m a d mi nistrati o n of t he dr u g or dr u g le vels ha ve 
bee n esta blis he d i n b o d y fl ui ds or tiss ues.  
•  
It c o ul d n ot be reas o na bl y ex plai ne d b y t he k n o w n c haracteristics of t he s u bject’s cli nical state, 
e n vir o n me ntal or t o x ic fact ors or ot her m o des of t hera p y  a d mi nistere d t o t he s u bject.  
•  
It disa p pears or decreases u p o n cessati o n of dr u g or re d ucti o n o n d ose a n d a p pears u p o n 
rec halle n ge. * 
•  
It f oll o ws a k n o w n res p o nse patter n t o t he s us pecte d dr u g. 
* T here are e x ce pti o ns w he n a n A E  d oes n ot disa p pear u p o n disc o nti n uati o n of t he dr u g, yet dr u g 
relate d ness clearl y ex ists. 
 
S o urce:  A da pte d fr o m C o bert B 2 0 1 2 (3 0 ) 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 4  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  H : Dr u gs t h at I n d uce C Y P 3 A 4   
T his is n ot a c o m pre he nsi ve list, a n d all c o nc o mita nt me dicati o ns s h o ul d be e val uat e d f or 
p ossi ble i nteracti o ns wit h bel u m os u dil . 
Ta ble 8 . 
E x a m ple s of Cli nic al I n d ucers of C Y P 3 A 4  
Str o n g I n d ucer  
M o der ate I n d ucer  
We a k I n d ucer  
A pal uta mi de  
Car ba maze pi ne  
E nzal uta mi de  
Mit ota ne  
P he n yt oi n  
Rifa m pi n  
St. J o h n’s w ort  
B ose nta n  
Efa vire nz  
Etra viri ne  
P he n o bar bital  
Pri mi d o ne  
Ar m o dafi nil  
M o dafi nil  
R ufi na mi de  
 
S o urce:  F D A. Dr u g De vel o p me nt a n d Dr u g I nteracti o ns.   
htt ps:// w w w.f da. g o v/ dr u gs/ de vel o p me nta p pr o val pr ocess/ d e vel o p me ntres o urces/ dr u gi nteracti o nsla beli n g/ u c m 0 9 3 6 6 4. ht m  
Ac cess e d 2 5  J un 2 0 2 1 (3 1 ) 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 5  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  I: Dr u gs T h at I n d uce a n d I n hi bit C Y P 1 A 2   
T his is n ot a c o m pre he nsi ve list, a n d all c o nc o mita nt me dicati o ns s h o ul d be e val uate d f or p ossi ble 
i nteracti o ns wit h bel u m os u dil . 
Ta ble 9 . 
E x a m ples of C li nic al In d ucers/ In hi bit ors of C Y P 1 A 2  
 
Str o n g  
M o der ate  
We a k  
I n d ucers 
Rifa m pi n  
P he n yt oi n  
Rifa m pi n  
Rit o na vir  
S m o ki n g  
T erifl u n o mi de  
--- 
I n hi bit o rs 
Ci pr ofl o xaci n  
E n o xaci n  
Fl u v o xa mi ne  
Met h o xsale n  
Me xileti ne  
Oral c o ntrace pti ves  
Ac ycl o vir  
All o p uri n ol  
Ci meti di ne  
P e gi nterfer o n α -2a  
Pi peri ne  
Zile ut o n  
 
S o urce: F D A. Dr u g De vel o p me nt a n d Dr u g I nteracti o ns.   
htt ps:// w w w.f da. g o v/ dr u gs/ de vel o p me nta p pr o val pr ocess/ d e vel o p me ntres o urces/ dr u gi nteracti o nsla beli n g/ u c m 0 9 3 6 6 4. ht m  
Ac cess e d 2 5 J u n 2 0 2 1 (3 1 ) 
 
 
 
V V- C LI N- 0 6 3 8 9 9 6 1. 0

B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 6  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  J : Dr u gs T h at Pr ol o n g Q Tc   
T his is n ot a c o m pre he nsi ve list, a n d all c o nc o mita nt me dicati o ns s h o ul d be e val uat e d f or 
p ossi ble i nteracti o ns wit h bel u m os u dil . 
Ta ble 1 0 . E x a m ples of D r u gs t h at P r ol o n g Q Tc 
Ge neric N a me  
•  
Aclar u bici n  
•  
Il o peri d o ne 
•  
A mi o dar o ne  
•  
Le v ofl o xaci n  
•  
A na greli de  
•  
Le v o me pr o mazi ne  
•  
Arse nic tri o xi de  
•  
Le v o met ha d yl acetate  
•  
Aste miz ole  
•  
Le v os ul piri de  
•  
Azit hr o m yci n  
•  
Mes ori dazi ne  
•  
Be pri dil  
•  
Met ha d o ne  
•  
C hl or o q ui ne  
•  
M o xifl o xaci n  
•  
C hl or pr o mazi ne  
•  
O n da nsetr o n  
•  
Cil ostaz ol  
•  
O xali plati n  
•  
Ci pr ofl o xaci n  
•  
Pa pa veri ne H Cl  
•  
Cisa pri de  
•  
Pe nta mi di ne  
•  
Cital o pra m  
•  
Pi m ozi de  
•  
Clarit hr o m yci n  
•  
Pr o b uc ol  
•  
Dis o p yra mi de  
•  
Pr ocai na mi de  
•  
D ofetili de  
•  
Pr o p of ol  
•  
D o m peri d o ne  
•  
Q ui ni di ne  
•  
D o ne pezil  
•  
R o xit hr o m yci n  
•  
Dr o ne dar o ne  
•  
Se v ofl ura ne  
•  
Dr o peri d ol  
•  
S otal ol  
•  
Er yt hr o m yci n  
•  
S parfl o xaci n  
•  
Escital o pra m  
•  
S ul piri de  
•  
Flecai ni de  
•  
S ult o pri de  
•  
Fl uc o naz ole  
•  
T erfe na di ne  
•  
Gatifl o xaci n  
•  
T erli pressi n  
•  
Gre pafl o xaci n  
•  
T er o dili ne  
•  
Hal ofa ntri ne  
•  
T hi ori dazi ne  
•  
Hal o peri d ol  
•  
Va n deta ni b  
•  
I b o gai ne 
 
•  
I b utili de 
 
S o urce:  htt ps://cre di ble me ds. or g/ p dfte m p/ p df/ C o m bi n e d List. p df   Ac cess e d 1 1  Ma y  2 0 2 0 (3 2 ) 
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B el u m os u dil  
Pr ot oc ol K D 0 2 5 -2 1 7  
Fi nal  
I N D 1 2 5 8 9 0 
 
 
 
 
 
 
 
Ka d m o n C or p orati o n  
P a ge 8 7  of 8 7  
C o nfi de nti al a n d Pr o priet ary  
0 1 Se p 2 0 2 1  
 
A p pe n di x  K : Pre d nis o ne D ose E q ui v ale nts   
C ha n ge i n c ortic oster oi d d oses will be a nal yze d b y usi n g pre d nis o ne d ose e q ui vale nts.  If s u bj ects are n ot 
usi n g pre d nis o ne as t he s yste mic c ortic oster oi d, t he n t he p re d nis o ne d ose e q ui vale nt will be deter mi ne d 
acc or di n g t o f oll o wi n g c o n versi o n rati os .  
O ne m g of pre d nis o ne is e q ui vale nt t o:  
•  4. 0 m g h y dr oc ortis o ne  
•  0. 8 m g Met h yl pre d nis ol o ne  
•  0. 1 5 m g De x a met has o ne  
•  1. 0 m g Pre d nis ol o ne  
•  0. 8  m g Tria mci n ol o ne  
 
S o urce:  Li u D  et al. 2 0 1 3 (3 3 )  
 
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