An Open Label Extension Study of Voxelotor (GBT440) Administered Orally to Participants With Sickle Cell Disease Who Have Participated in Voxelotor Clinical Trials
Phase: PHASE3
Conditions: Sickle Cell Disease
Sponsor: Pfizer

C LI NI C A L S T U D Y P R O T O C O L
St u d y N u m ber
G B T 4 4 0 -0 3 4 ( C 5 3 4 1 0 2 2)
St u d y Title
A n O pe n La bel E xte nsi o n St u d y  of V o xel ot or ( G B T 4 4 0) 
A d mi nistere d Orall y t o Partici pa nts wit h Sic kle Cell Disease W h o 
Ha ve Partici pate d i n V o xel ot or Cli nical Trials 
I n vesti g ati o n al 
Pr o d uct
V o xel ot or ( G B T 4 4 0) 
I N D
1 2 1, 6 9 1
E u dr a C T
2 0 1 7 -0 0 4 0 4 5 -2 5
S p o ns or Le g al 
A d dress
Gl o bal Bl o o d T hera pe utics, I nc., a w h oll y  o w ne d s u bsi diar y of Pfizer 
I nc.
1 7 1 O y ster P oi nt B o ule var d, S uite 3 0 0
S o ut h Sa n Fra ncisc o, C A 9 4 0 8 0
U nite d States of A merica
A m e n d me nt 3. 0
1 8 Dece m ber 2 0 2 3
A m e n d me nt 2. 0
1 9 Dece m ber 2 0 1 9 
A m e n d me nt 1. 0
1 4 J u ne 2 0 1 8
Ori gi n al Versi o n 
0 9 Oct o ber 2 0 1 7
T his a me n d me nt i nc or p orates all re visi o ns t o date, i ncl u di n g a me n d me nts ma de at t he 
re q uest of c o u ntr y healt h a ut h orities a n d I R Bs/ E Cs a n d a ny pr ot oc ol a d mi nistrati ve c ha n ge 
letter(s).
C O N FI D E N TI A L
T he i nf or mati o n i n t his st u d y pr ot oc ol is strictl y c o nfi de ntial a n d is a vaila ble f or re vie w t o 
I n vesti gat ors, st u d y ce nter pers o n nel, t he et hics c o m mittee a n d t he healt h a ut h orities. It 
will n ot be discl ose d t o t hir d parties wit h o ut writte n a ut h orizati o n fr o m t he S p o ns or, e xce pt 
t o o btai n i nf or me d c o nse nt fr o m pers o ns recei vi n g t he st u dy treat me nt. O nce t he pr ot oc ol 
is si g ne d, its ter ms are bi n di n g f or all parties.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2
S U M M A R Y O F C H A N G E S 
A m e n d me nt 3 (1 8 Dece m ber 2 0 2 3)
O ver all R ati o n ale f or t he A me n d me nt: 

T o i nc or p orate c ha n ges pre vi o usl y i m ple me nte d via pr ot oc ol clarificati o n me m os

T o ali g n t he pr ot oc ol wit h t he Pfizer Pr ot oc ol Te m plate a n d Sta n dar d O perati n g 
Pr oce d ures

N ote: t he c ha n ges bel o w are n ot d ue t o a n y i ncrease i n safet y si g nals
Pr ot oc ol A me n d me nt S u m m ar y of C h a n ges T a ble
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
N o n -s u bst a nti al M o dific ati o n(s)
Re m o ve d na me of St u d y 
Direct or
T his secti o n was re m o ve d 
beca use it c o ntai ns pers o nal 
pr otecte d data
Title Pa ge
Re m o ve d State me nt of 
A p pr o val a n d C o m plia nce
State me nt of A p pr o val a n d 
C o m plia nce is n ot liste d o n 
Pfizer pr ot oc ols per Pfizer 
S O Ps
A p pr o val pa ge
A d de d la n g ua ge a b o ut 
ide ntificati o n of Si n gle 
R efere nce S afet y D oc u me nt 
( S R S D) 
T o s u p p ort St u d y tra nsiti o n t o 
Pfizer pr oce d ures
1. 3. 1 Safet y 
U p date d t he list of e xa m ples 
of m o derate a n d str o n g 
C Y P 3 A 4 i n d ucers
T o pr o vi de u p -t o-date 
g ui da nce t o I n vesti gat ors per 
t he latest list of e xa m ples 
pr o vi de d b y t he F D A a n d 
ali g n wit h ot her v o xel ot or 
cli nical st u d y pr ot oc ols
5. 5. 3 Pr o hi bite d Me dicati o ns
A d d e d la n g ua ge re gar di n g 
t he ma xi m u m v ol u me of 
bl o o d t o be c ollecte d i n 
a d olesce nts
F or c o m plia nce wit h W H O 
g ui deli nes
7. 1. 5 La b orat or y Assess me nts
A d de d safet y re p orti n g 
clarificati o ns
T o s u p p ort St u d y tra nsiti o n t o 
Pfizer P har mac o vi gila nce 
pr ocesses a n d s yste ms
7. 2. 2. 1 Ge neral
A d de d la n g ua ge a n d a ne w 
a p pe n di x f or re p orti n g a n d 
f oll o w-u p assess me nts f or 
p ote ntial dr u g -i n d uce d li ver 
i nj ur y ( DI LI) e ve nts
T o s u p p ort st u d y tra nsiti o n t o 
Pfizer P har mac o vi gila nce 
pr ocesses a n d s yste ms
7. 2. 2. 3 A b n or mal La b orat or y 
Val ues
A p pe n di x 2 ( ne w a p pe n dix)
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3
Descri pti o n of C h a n ge
Brief R ati o n ale
Secti o n # a n d N a me
A d de d la n g ua ge f or re p orti n g 
A Es a n d S A Es after t he e n d 
of A E/ S A E acti ve c ollecti o n 
peri o d
T o s u p p ort St u d y tra nsiti o n t o 
Pfizer P har mac o vi gila nce 
pr ocesses a n d s yste ms
7. 2. 3 Seri o us A d verse E ve nts, 
Seri o us A d verse Dr u g 
Reacti o ns, a n d Re q uire me nts 
f or I m me diate Re p orti n g
Re vise d la n g ua ge o n 
re p orti n g o ver d ose
T o ali g n wit h Pfizer’s safet y 
re p orti n g pr ocess
7. 2. 4 Re p orti n g O ver d ose
A d de d la n g ua ge re gar di n g 
e n vir o n me ntal a n d 
occ u pati o nal e x p os ure as well 
as e x p os ure d uri n g pre g na nc y 
a n d breastfee di n g. Pre vi o us 
secti o n 8. 2. 4 Re p orti n g 
P re g na nc y has bee n re place d 
b y t he la n g ua ge i n secti o n 7. 3
T o s u p p ort St u d y tra nsiti o n t o 
Pfizer P har mac o vi gila nce 
pr ocesses a n d s yste ms
7. 3 E n vir o n me ntal E x p os ure, 
E x p os ure D uri n g Pre g na nc y 
or Breastfee di n g, a n d 
Occ u pati o nal E x p os ure ( ne w 
secti o n
A d de d la n g ua ge re gar di n g 
t he defi niti o n a n d re p orti n g of 
me dicati o n err ors
T o s u p p ort St u d y tra nsiti o n t o 
Pfizer P har mac o vi gila nce 
pr ocesses a n d s yste ms
7. 4 Me dicati o n Err ors ( ne w 
secti o n)
A d de d or re vise d la n g ua ge 
re gar di n g access t o me dical 
m o nit or a n d re g ulat or y 
o bli gati o ns, disse mi nati o n of 
cli nical st u d y data, 
p u blicati o n p olic y, data 
q ualit y ass ura nce, st u d y a n d 
site start a n d cl os ure, data
pr otecti o n, a n d i nf or me d 
c o nse nt
T o s u p p ort St u d y tra nsiti o n t o 
Pfizer Pr ot oc ol Te m plate a n d 
Sta n dar d O perati n g 
Pr oce d ures
1 0. 3 ( S p o ns or’s Me dicall y 
Q ualifie d I n di vi d ual) ( ne w)
1 1. Re g ulat or y, Et hical, 
Le gal, a n d O versi g ht 
O bli gati o ns (i ncl u des se veral 
ne w s u bsecti o ns)
1 2. Data Ha n dli n g a n d 
Rec or d Kee pi n g
1 3. P u blicati o n P olic y
I ncl usi o n of Pfizer st u d y 
n u m ber
T o s u p p ort tra nsiti o n t o Pfizer 
pr ocesses
At vari o us p oi nts t hr o u g h o ut 
t he pr ot oc ol
M i n or clarificati o ns a n d t y p o 
c orrecti o ns acr oss t he 
pr ot oc ol
F or clarificati o n p ur p oses
At vari o us p oi nts t hr o u g h o ut
t he pr ot oc ol
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4
T A B L E O F C O N T E N T S
S U M M A R Y O F C H A N G E S .....................................................................................................2
LI S T O F T A B L E S ..................................................................................................................... 8
P R O T O C O L  S Y N O P SI S .......................................................................................................... 9
1. B A C K G R O U N D I N F O R M A TI O N .................................................................................... 1 2
1. 1. Na me a n d Descri pti o n of I n vesti gati o nal Pr o d uct .................................................. 1 2
1. 2. S u m mar y  of Fi n di n gs fr o m Rele va nt N o ncli nical Trials........................................ 1 2
1. 3. S u m mar y  of t he V o xel ot or Cli nical Pr o gra m ......................................................... 1 2
1. 3. 1. Safet y .......................................................................................................... 1 2
1. 3. 2. Efficac y ....................................................................................................... 1 3
1. 4. Descri pti o n a n d J ustificati o n f or R o ute of A d mi nistrati o n, D osa ge, D osa ge 
Re gi me n, a n d Treat me nt Peri o d(s) ............................................................................ 1 6
1. 5. Trial C o n d uct ........................................................................................................... 1 6
1. 6. Descr i pti o n of t he P o p ulati o n t o be St u die d............................................................ 1 6
1. 7. Rati o nale f or t his St u d y ........................................................................................... 1 6
2. T RI A L O BJ E C TI V E S A N D P U R P O S E ............................................................................. 1 6
3. I N V E S TI G A T I O N A L PL A N ..............................................................................................1 6
3. 1. O verall St u d y  Desi g n..............................................................................................1 6
3. 1. 1. E n d p oi nts .................................................................................................... 1 6
3. 1. 1. 1. Safet y ......................................................................................... 1 6
3. 1. 1. 2. Sic kle Cell Disease ( S C D) -Relate d C o m plicati o ns ................... 1 6
3. 1. 1. 3. Treat me nt Effect ........................................................................ 1 7
3. 1. 2. Desi g n ......................................................................................................... 1 7
3. 2. N u m ber of S u bjects ................................................................................................. 1 7
3. 3. Treat me nt Assi g n me nt ............................................................................................ 1 7
3. 4. Criteria f or St u d y  Ter mi nati o n................................................................................ 1 7
4. S E L E C TI O N A N D WI T H D R A W A L  O F S U BJ E C T S.......................................................1 8
4. 1. S u bject I ncl usi o n Criteria ........................................................................................ 1 8
4. 2. S u bject E xcl usi o n Criteria ....................................................................................... 1 8
4. 3. S u bject Wit h dra wal Criteria .................................................................................... 1 8
5. T R E A T M E N T O F S U BJ E C T S ........................................................................................... 1 9
5. 1. St u d y  Dr u g I nf or mati o n.......................................................................................... 2 0
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5
5. 2. St u d y  Dr u g Dis pe nsati o n ........................................................................................ 2 0
5. 3. Dr u g Acc o u nta bilit y a n d Rete nti o n ......................................................................... 2 0
5. 4. D ose M o dificati o n ................................................................................................... 2 1
5. 5. C o nc o mita nt Me dicati o ns ....................................................................................... 2 4
5. 5. 1. Pri or a n d C o nc o mita nt Me dicati o ns ........................................................... 2 4
5. 5. 2. All o we d C o nc o mita nt Me dicati o ns ............................................................ 2 4
5. 5. 3. Pr o hi bite d Me dicati o ns ............................................................................... 2 4
5. 5. 4. Ma na ge me nt of O ver d ose ........................................................................... 2 5
5. 6. Fertilit y / C o ntrace pti ve Re q uire me nts ..................................................................... 2 6
5. 6. 1. I nstr ucti o ns f or Fe male Partici pa nts of C hil d -Beari n g P ote ntial ................ 2 6
5. 6. 2. Fe male Partici pa nts of N o n -C hil d -Beari n g P ote ntial ................................. 2 6
5. 6. 3. I nstr ucti o ns f or Male Partici pa nts ...............................................................2 6
5. 6. 4. Acce pta ble F or ms of C o ntrace pti o n ........................................................... 2 6
5. 7. Treat me nt C o m plia nce ............................................................................................ 2 7
5. 8. Ra n d o mizati o n a n d Bli n di n g ................................................................................... 2 7
6. A S S E S S M E N T O F T R E A T M E N T E F F E C T .....................................................................2 7
6. 1. He m ol y tic A ne mia .................................................................................................. 2 7
7. A S S E S S M E N T O F S A F E T Y ..............................................................................................2 8
7. 1. Safet y Para meters .................................................................................................... 2 8
7. 1. 1. De m o gra p hic/ Me dical Hist or y ................................................................... 2 8
7. 1. 2. Vital Si g ns .................................................................................................. 2 8
7. 1. 3. P h y sical E xa mi nati o n ................................................................................. 2 8
7. 1. 4. Electr ocar di o gra m ( E C G) ........................................................................... 2 9
7. 1. 5. L a b orat or y Assess me nts.............................................................................2 9
7. 1. 5. 1. He mat ol o g y  ( Da y 1 t hr o u g h Wee k 4 8)..................................... 2 9
7. 1. 5. 2. Bl o o d C he mistr y ( Da y  1 t hr o u g h Wee k 4 8) ............................. 3 0
7. 1. 5. 3. E x pl orat or y  Meas ures Relate d t o S C D Pat h o p h ysi ol o g y 
( Da y 1, Wee ks 1 2, 2 4, a n d 4 8).......................................................... 3 0
7. 1. 5. 4. Pre g na nc y  Test ( All visits)........................................................ 3 1
7. 1. 6. S C D -Relate d C o m plicati o ns ....................................................................... 3 1
7. 1. 6. 1. Vas o -Occl usi ve Crisis ( V O C) ................................................... 3 1
7. 1. 7. Ot her S C D -relate d C o m plicati o ns..............................................................3 2
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 6
7. 2. A d verse a n d Seri o us A d verse E ve nts...................................................................... 3 2
7. 2. 1. A d verse E ve nts ........................................................................................... 3 2
7. 2. 1. 1. Defi niti o n of A d verse E ve nts .................................................... 3 2
7. 2. 1. 2. Se verit y  of A d verse E ve nts.......................................................3 3
7. 2. 1. 3. Relati o ns hi p t o I n vesti gati o nal Pr o d uct .................................... 3 4
7. 2. 1. 4. U ne x pecte d A d verse Reacti o ns ................................................. 3 4
7. 2. 2. A d v erse E ve nt Re p orti n g ............................................................................ 3 4
7. 2. 2. 1. Ge neral ...................................................................................... 3 4
7. 2. 2. 2. Dia g n osis Vers us Si g ns a n d S y m pt o ms .................................... 3 5
7. 2. 2. 3. A b n or mal La b orat or y  Val ues.................................................... 3 6
7. 2. 2. 4. Pree xisti n g Me dical C o n diti o ns ................................................ 3 6
7. 2. 2. 5. W orse ni n g of Sic kle Cell Disease ............................................. 3 6
7. 2. 3. Seri o us A d verse E ve nts, Seri o us A d verse Dr u g Reacti o ns, a n d 
Re q uire me nts f or I m me diate Re p orti n g ........................................................... 3 6
7. 2. 3. 1. Re p orti n g S us pecte d U ne x pecte d Seri o us A d verse 
Reacti o ns ( S U S A Rs) a n d Ur ge nt Safet y Iss ues ................................ 3 7
7. 2. 4. Re p orti n g O ver d ose .................................................................................... 3 7
7. 3. E n vir o n me ntal E x p os ure, E x p os ure D uri n g Pre g na nc y  or Breastfee di n g, a n d 
Occ u pati o nal E x p os ure ..............................................................................................3 8
7. 3. 1. E x p os ure D uri n g Pre g na n c y ....................................................................... 3 8
7. 3. 2. E x p os ure D uri n g Breastfee di n g .................................................................. 4 0
7. 3. 3. Occ u pati o nal E x p os ure ............................................................................... 4 0
7. 4. L ac k Of Efficac y ..................................................................................................... 4 0
7. 5. Me dicati o n Err ors .................................................................................................... 4 0
7. 6. Data a n d Safet y M o nit ori n g B oar d ......................................................................... 4 1
8. BI O S T A T I STI C S ................................................................................................................ 4 1
8. 1. Statistical Met h o ds .................................................................................................. 4 1
8. 1. 1. St u d y  E n d p oi nts.......................................................................................... 4 2
8. 1. 1. 1. Safet y ......................................................................................... 4 2
8. 1. 1. 2. Fre q ue nc y  of S C D-Relate d C o m plicati o ns ............................... 4 2
8. 1. 1. 3. Res p o nse i n He m ol y tic A ne mia................................................ 4 2
8. 2. Sa m ple Size ............................................................................................................. 4 3
8. 3. L e vel of Si g nifica nce ...............................................................................................4 3
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 7
8. 4. Statistical Criteria f or Ter mi nati o n of t he Trial ...................................................... 4 3
8. 5. Missi n g, U n use d, or S p uri o us Data ......................................................................... 4 3
8. 6. De viati o n fr o m t he Statistical A nal y sis Pla n........................................................... 4 3
8. 7. A nal y sis P o p ulati o n................................................................................................. 4 3
9. DI R E C T A C C E S S T O S O U R C E D A T A/ D O C U M E N T S .................................................. 4 3
9. 1. S o urce Data ............................................................................................................. 4 3
9. 2. Data C ollecti o n ........................................................................................................ 4 4
9. 3. Ess e ntial D oc u me ntati o n Re q uire me nts.................................................................. 4 4
1 0. Q U A LI T Y C O N T R O L  A N D Q U A LI T Y A S S U R A N C E ................................................. 4 4
1 0. 1. M o nit ori n g ............................................................................................................. 4 4
1 0. 2. L a b orat or y Accre ditati o n ...................................................................................... 4 4
1 0. 3. S p o ns or’s Me dicall y  Q ualifie d I n di vi d ual............................................................ 4 5
1 1. R E G U L A T O R Y, E T HI C A L , L E G A L, A N D O V E RSI G H T O B LI G A TI O N S ................ 4 5
1 1. 1. Re g ulat or y  an d Et hical C o nsi derati o ns ................................................................. 4 5
1 1. 2. Re p orti n g of Safet y I ss ues a n d Seri o us Breac hes of t he Pr ot oc ol or I C H 
G C P ........................................................................................................................... 4 6
1 1. 3. I nf or me d C o nse nt a n d Asse nt Pr ocess .................................................................. 4 6
1 1. 3. 1. I nf or me d C o nse nt ..................................................................................... 4 6
1 1. 3. 2. I nf or me d Asse nt ........................................................................................ 4 7
1 1. 4. Data Pr otecti o n ...................................................................................................... 4 8
1 2. D A T A H A N D LI N G A N D R E C O R D K E E PI N G ..............................................................4 9
1 2. 1. I ns pecti o n of Rec or ds ............................................................................................ 4 9
1 2. 2. Rete nti o n of Rec or ds ............................................................................................. 4 9
1 2. 3. Discl os ure of I nf or mati o n ..................................................................................... 5 0
1 2. 4. Disse mi nati o n of Cli nical St u d y  Data................................................................... 5 1
1 2. 5. Data Q ualit y Ass ura nce ......................................................................................... 5 2
1 2. 6. St u d y  a n d Site Start a n d Cl os ure........................................................................... 5 3
1 3. P U B LI C A TI O N P O LI C Y ................................................................................................. 5 4
1 4. R E F E R E N C E S ..................................................................................................................5 5
1 5. A P P E N DI C E S ...................................................................................................................5 6
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 8
LI S T O F T A B L E S
Ta ble 1.
Cli nical St u dies i n S C D wit h V o xel ot or ...................................................1 4
Ta ble 2.
D ose M o dificati o n G ui deli nes f or St u d y  Dr u g-Relate d A d verse 
E ve nts ....................................................................................................... 2 1
Ta ble 3.
D ose M o dificati o n G ui deli nes f or St u d y  Dr u g-Relate d Ras h .................. 2 3
Ta ble 4.
Se nsiti ve C Y P 3 A 4 S u bstrates wit h Narr o w T hera pe utic Ra n ge.............. 2 5
Ta ble 5.
E xa m ples of M o derate a n d Str o n g C Y P I n d ucers .................................... 2 5
Ta ble 6.
A d diti o nal Pr o hi bite d Me dicati o ns ........................................................... 2 5
Ta ble 7.
Gra di n g f or A d verse E ve nts N ot C o vere d i n t he N CI  C T C A E................ 3 3
Ta ble 8.
Re p orti n g of Me dicati o n Err ors ................................................................ 4 1
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 9
P R O T O C O L S Y N O P SI S
P R O T O C O L S Y N O P SI S
P R O T O C O L TI T L E: A n O pe n La bel E xte nsi o n St u d y of V o xel ot or ( G B T 4 4 0) A d mi nistere d 
Orall y t o Partici pa nts wit h Sic kle Cell Disease W h o Ha ve Partici pate d i n V o xel ot or Cli nical 
Trials
P R O T O C O L N U M B E R: G B T 4 4 0- 0 3 4/ C 5 3 4 1 0 2 2
O B J E C TI V E S
T he o bjecti ve of t his o pe n -la bel e xte nsi o n ( O L E) st u d y is t o assess t he l o n g-ter m safet y a n d 
treat me nt effect of v o x el ot or i n partici pa nts w h o ha ve c o m plete d treat me nt i n st u d y G B T 4 4 0-
0 3 1, usi n g t he f oll o wi n g para meters:
1.
Safet y base d u p o n A Es, cli nical la b orat or y tests, p h ysical e xa mi nati o ns ( P E) a n d ot her 
cli nical meas ures.  
2.
Fre q ue nc y of sic kle cell disease ( S C D) -relate d c o m plicati o ns. 
He m ol ytic a ne mia as meas ure d b y he mat ol o gical la b orat or y para meters (e g, he m o gl o bi n, 
retic ul oc ytes a n d u nc o nj u gate d bilir u bi n).
E N D P OI N T S
1.
Safet y e n d p oi nts i ncl u de A Es, cli nical la b orat or y tests, p h ysical e xa mi nati o ns a n d ot her 
cli nical meas ures.
2.
Fre q ue nc y of S C D -relate d c o m plicati o ns of l o n g-ter m d osi n g wit h v o xel ot or.
He m ol ytic a ne mia as meas ure d b y he mat ol o gical la b orat or y para meters (e g, he m o gl o bi n, 
retic ul oc ytes a n d u nc o nj u gate d bilir u bi n). 
S T U D Y D E SI G N
T his o pe n la bel e x te nsi o n ( O L E), m ulti-ce nter st u d y will be c o n d ucte d at a p pr o xi matel y 1 0 0 
cli nical sites gl o ball y a n d will be a vaila ble t o eli gi ble partici pa nts fr o m st u d y G B T 4 4 0 - 0 3 1. 
T he st u d y will e nr oll partici pa nts fr o m G B T 4 4 0 -0 3 1 (a p pr o xi matel y 4 3 5) u n der a n y of t he 
f oll o wi n g c o n diti o ns:

Partici pa nt has c o m plete d 7 2 wee ks of treat me nt re gar dless of d ose selecti o n f or 
G B T 4 4 0- 0 3 1

D ose selecti o n has occ urre d f or G B T 4 4 0 -0 3 1 a n d partici pa nt is o n n o n -selecte d d ose o n 
G B T 4 4 0- 0 3 1

G B T 4 4 0- 0 3 1 st u d y i nteri m data a nal ysis a n d/ or st u d y m o dificati o ns ha ve occ urre d
G B T 4 4 0- 0 3 1 st u d y has c o m plete d
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 0
T R E A T M E N T
All partici pa nts will recei ve dail y v o xel ot or treat me nt. 
Partici pa nts ma y recei ve st u d y dr u g as l o n g t he y c o nti n ue t o recei ve cli nical be nefit w hic h 
o ut wei g hs ris k as de ter mi ne d b y t he I n vesti gat or a n d/ or u ntil t he partici pa nt has access t o 
v o xel ot or fr o m a n alter nati ve s o urce (i.e., c o m mercializati o n or t hr o u g h a ma na ge d access 
pr o gra m).
I N C L U SI O N/ E X C L U SI O N C RI T E RI A
S u bject I ncl usi o n Criteri a
1.
Male or fe male st u d y partici pa nts wit h S C D w h o partici pate d a n d recei ve d st u d y 
treat me nt i n st u d y G B T 4 4 0- 0 3 1. 
N ote: Partici pa nts i n G B T 4 4 0 -0 3 1 w h o disc o nti n ue d st u d y dr u g d ue t o a n A E, b ut w h o 
re mai ne d o n st u d y ma y be eli gi ble f or treat me nt i n t his st u d y pr o vi de d t he A E d oes n ot 
p ose a ris k f or treat me nt wit h v o xel ot or.
2.
Fe males of c hil d -beari n g p ote ntial are re q uire d t o ha ve a ne gati ve uri ne pre g na nc y test 
pri or t o d osi n g o n Da y 1.
3.
Fe male partici pa nts of c hil d -beari n g p ote ntial m ust use hi g hl y effecti ve me t h o ds of 
c o ntrace pti o n t o 3 0 da ys after t he last d ose of st u d y dr u g. Male partici pa nts m ust use 
barrier met h o ds of c o ntrace pti o n t o 3 0 da ys after t he last d ose of st u d y dr u g.
4.
Partici pa nt has pr o vi de d writte n i nf or me d c o nse nt or asse nt (t he I C F m ust be re vi e we d 
a n d si g ne d b y eac h partici pa nt; i n t he case of pe diatric partici pa nts, b ot h t he c o nse nt of 
t he partici pa nt’s le gal re prese ntati ve or le gal g uar dia n, a n d t he partici pa nt’s asse nt m ust 
be o btai ne d).
S u bject E xcl usi o n Criteri a
1.
Fe male w h o is breast -fee di n g or pre g na nt.
2.
Partici pa nt wit h dre w c o nse nt fr o m St u d y G B T 4 4 0 - 0 3 1.
3.
Partici pa nt was l ost t o f oll o w -u p fr o m St u d y G B T 4 4 0 - 0 3 1.
4.
Partici pa nt re q uiri n g c hr o nic dial ysis.
A n y me dical, ps yc h ol o gical, safet y, or be ha vi oral c o n diti o ns, w hic h, i n t he o pi ni o n of t he 
I nvesti gat or, ma y c o nf o u n d safet y i nter pretati o n, i nterfere wit h c o m plia nce, or precl u de 
i nf or me d c o nse nt.
S T A TI S TI C A L M E T H O D S
Statistical pr o gra m mi n g a n d a nal yses will be perf or me d usi n g esta blis he d statistical met h o ds. 
Details of all pla n n e d a nal yses will be s pecifie d i n a se parate statistical a nal ysis pla n ( S A P). 
T he st u d y data will be re p orte d usi n g s u m mar y ta bles, fi g ures, a n d data listi n gs. C o nti n u o us 
varia bles will be s u m marize d usi n g mea n, sta n dar d de viati o n ( S D), me dia n, mi ni m u m, a n d 
ma xi m u m. Cate g orical varia bles will be s u m marize d b y prese nti n g t he n u m ber (fre q ue nc y) a n d 
perce nta ge i n eac h cate g or y.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 1
St u d y E n d p oi nts 
S afet y
Safet y data a nal ysis will be perf or me d o n all partici pa nts e nr olle d i n t he st u d y. A treat me nt -
e mer ge nt a d verse e ve nt ( T E A E) is defi ne d as a n A E t hat e mer ges o n or after i nitiati o n of st u d y 
dr u g ( ha vi n g bee n a bse nt pretreat me nt), or a n A E t hat e xiste d pretr eat me nt a n d w orse ne d o n 
treat me nt (relati ve t o t he pretreat me nt state). T he i nci de nce of T E A Es will be ta b ulate d b y 
s yste m or ga n class ( S O C), preferre d ter m, se verit y a n d relati o ns hi p t o st u d y dr u g. A Es 
c o nsi dere d t o be relate d b y t he I n vesti gat or will be s u m marize d. A Es will be re p orte d b y 
se verit y a n d relate d ness t o st u d y treat me nt a n d classifie d via t he Me dical Dicti o nar y f or 
Re g ulat or y Acti vities ( Me d D R A).
C ha n ges i n cli nical la b orat or y data ( he mat ol o g y, ser u m c he mistr y, 
 
) will be s u m marize d. 
F or t he la b orat or y safet y data, o ut of ra n ge val ues will be fla g ge d i n t he data listi n gs a n d a list 
of cli nicall y si g nifica ntl y a b n or mal val ues will be prese nte d.
Fre q ue nc y of S C D -Rel ate d C o m plic ati o ns
O ver t he c o urse of t he treat me nt peri o d, t he fre q ue nc y of S C D c o m plicati o ns f or eac h 
partici pa nt will be rec or de d. S C D c o m plicati o ns ma y i ncl u de t he f oll o wi n g: V O C ( Vas o -
Occl usi ve Crisis), ac ute c hest s y n dr o me, he patic se q uestrati o n, le g ulcers, pria pis m, p ul m o nar y 
h y perte nsi o n, reti n o pat h y, scleral icter us, s ple nic se q uestrati o n, a n d str o ke. T he i nci de nce a n d 
rate of eac h c o m plicati o n a n d t he t otalit y of all S C D-relate d c o m plicati o ns will be c o m p ute d 
a n d t he n c o m pare d t o t h ose o bser ve d i n t he G B T 4 4 0 -0 3 1 st u d y.  
T her a pies Ass oci ate d wit h V O C
D uri n g t he treat me nt peri o d, R B C ( Re d Bl o o d Cell) tra nsf usi o n a n d o pi oi d usa ge will be 
rec or de d. T he i nci de nce a n d rate of t hese t hera pies will be calc ulate d a n d c o m pare d t o t h ose 
o bser ve d i n t he G B T 4 4 0 -0 3 1 st u d y.
Res p o nse i n He m ol ytic A ne mi a
At eac h sc he d ule d la b orat or y assess me nt, he mat ol o g y a n d ser u m c he mistr y will be meas ure d t o 
deter mi ne l o n git u di nal d ura bilit y of res p o nse wit h re gar ds t o he m ol ytic a ne mia. Of partic ular 
i nterest are he m o gl o bi n, bilir u bi n, a n d retic ul oc yte c o u nts. T here will be t w o baseli ne val ues 
use d t o descri be efficac y a n d d ura bilit y: ( 1) Baseli ne deri ve d fr o m t he pre -d ose he mat ol o g y 
meas ure me nts o btai ne d d uri n g t he G B T 4 4 0 -0 3 1 st u d y a n d ( 2) He mat ol o g y meas ure me nts 
o btai ne d via pre -d ose o n Da y 1 i n t his st u d y. C ha n ge fr o m baseli ne, a n d perce nt c ha n ge fr o m 
baseli ne f or t he t w o af ore me nti o ne d baseli ne val ues will be c o m p ute d t o deter mi ne tre n ds o ver 
t he d urati o n of treat me nt.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)
C CI

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 2
1. B A C K G R O U N D I N F O R M A TI O N
Sic kle Cell Disease ( S C D) is a rare, de vastati n g, a n d de bilitati n g disease mar ke d b y  t he 
pat h o p h y si ol o gic feat ures of he m ol ytic a ne mia, vas o- occl usi o n, a n d pr o gressi ve e n d-or ga n 
da ma ge, wit h a cli nical c o urse c haracterize d b y life -l o n g disa bilit y a n d earl y deat h. I n 
a d diti o n t o u n pre dicta ble a n d rec urre nt e pis o des of se ve re pai n, c o m m o nly referre d t o as 
pai nf ul crises, a s ys te mic vasc ul o pat h y lea ds t o c hr o nic a n d pr o gressi ve tiss ue i nj ur y acr oss 
m ulti ple or ga n s ys te ms. M ulti ple pat h o p h ysi ol o gic mec ha nis ms li kely c o ntri b ute t o t he 
s yste mic vasc ul o pat h y, i ncl u di n g, i m p orta ntl y, c hr o nic he m ol ytic a ne mia (R ot her, 2 0 0 5 ). 
O n 2 5 N o ve m ber 2 0 1 9, t he U nite d States ( U S) 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 t he st u d y dr u g v o xel ot or, n o w k n o w n b y t he tra de na me O x br yta ™. O x br y ta is 
i n dicate d f or t he treat me nt of sic kle cell disease i n a d ults a n d pe diatric patie nts 1 2 years of 
a ge a n d ol der. 
I n this trial, t he S p o ns or will be st u d y i n g t he ris ks a n d be nefits of l o n g-ter m treat me nt i n 
partici pa nts pre vi o usl y treate d i n G B T 4 4 0- 0 3 1.
1. 1. N a me a n d Descri pti o n of I n vesti g ati o n al Pr o d uct
V o xel ot or is a s mall m olec ule all osteric m o d ulat o r of he m o gl o bi n ( H b) o x y ge n affi nity, t hat 
was de vel o pe d b y Gl o bal Bl o o d T hera pe utics ( G B T) f or t he treat me nt of sic kle cell disease 
( S C D). V o xel ot or is a d mi nistere d orally.
1. 2. S u m m ar y of Fi n di n gs fr o m Rele v a nt N o ncli nic al Tri als
I nf or mati o n re gar di n g n o ncli nical p har mac ol o g y (i ncl u di n g safety p har mac ol o g y a n d 
meta b olis m) a n d t o xic ol o g y  is pr o vi de d i n t he v o xel ot or I n vesti gat or's Br oc h ure (I B), 
pr o vi de d u n der se parate c o ver.
1. 3. S u m m ar y of t he V o xel ot or Cli nic al Pr o gr a m
T he cli nical acti vit y, safet y, a n d p har mac o ki netics of v o xel ot or ha ve bee n or are bei n g 
assesse d i n 4 cli nical st u dies i n a d ults a n d pe diatric partici pa nts wit h S C D ( Ta ble 1 ).  
1. 3. 1. S afet y
I n t he P hase 3 ra n d o mize d c o ntr olle d trial ( G B T 4 4 0 - 0 3 1) i n a d ults a n d a d olesce nts wit h 
S C D, t he m ost fre q ue ntl y ( > 1 0 %) re p orte d T E A Es i ncl u de d: hea dac he, diarr hea, na usea, 
art hral gia, a b d o mi nal pai n, fati g ue, ras h, u p per res pirat or y  tract i nfecti o n, p yre xia, pai n i n 
e xtre mit y, bac k pai n, v o miti n g, pai n, n o n -car diac c hest pai n, a n d a b d o mi nal pai n u p per 
( Vic h nis k y 2 0 1 9). T he maj orit y of t hese T E A Es were Gra de 1 t o Gra de 2 i n se verity a n d 
res ol ve d. O verall, t he T E A Es were si milar acr oss all treat me nt gr o u ps ( 1 5 0 0 m g v o xel ot or, 
9 0 0 m g v o xel ot or, or place b o) e xce pt f or diarr hea w hic h is hi g her i n t he v o xel ot or treat me nt 
gr o u ps t ha n place b o. T he m ost c o m m o n treat me nt- relate d T E A E was diarr hea. 
O verall, t he safet y pr ofile f or T E A Es was si milar bet wee n a d olesce nts a n d a d ults.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 3
A d diti o nal i nf or mati o n o n t he safet y of v o xel ot or is descri be d i n t he c urre nt versi o n of t he 
v o xel ot or I B, w hic h is t he Si n gle Refere nce Safet y  D oc u me nt ( S R S D) f or t his st u d y.
1. 3. 2. Effic ac y
Data fr o m t he P hase 3 ra n d o mize d c o ntr olle d trial ( G B T 4 4 0 - 0 3 1) de m o nstrate d t hat 
a d ministrati o n of v o xel ot or i n partici pa nts wit h S C D res ulte d i n a statisticall y  si g nifica nt a n d 
cli nicall y mea ni n gf ul i m pr o ve me nt i n H b ( > 1 g/ d L i ncrease) at 2 4 wee ks c o m pare d t o 
place b o ( Vic hi ns k y , 2 0 1 9). C o nc o mita nt wit h t he i m pr o ve d a ne mia t here was a re d ucti o n i n 
la b orat or y meas ures of he m ol ysis, i ncl u di n g retic ul oc ytes, L D H (L actate D e h y dr o ge nase ), 
a n d i n direct bilir u bi n. A d diti o nall y, i n t he P hase 1/ 2 st u d y ( G B T 4 4 0-0 0 1) a n d e xte nsi o n 
st u d y ( G B T 4 4 0-0 2 4), treat me nt wit h v o xe l ot or le d t o re d ucti o ns i n t he perce nta ge of sic kle d 
re d cells i n t he peri p heral bl o o d (H o war d, 2 0 1 9 ).
A d diti o nal i nf or mati o n o n t he efficac y  of v o xel ot or is descri be d i n t he c urre nt versi o n of t he 
v o xel ot or I B.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 4
T a ble 1.
Cli nic al St u dies i n S C D wit h V o xel ot or
St u d y 
N o./ P h ase
Sites/ 
L oc ati o n
St u d y 
T y pe
St u d y 
P o p ul ati o n
V o xel ot or D oses 
E v al u ate d
Tre at m e nt 
D ur ati o n
N o. of S u bjects
St at us of 
e nr oll me nt
G B T 4 4 0 -0 0 1/
P hase 1/ 2
1 Site/
U nite d 
Ki n g d o m
Si n gle a n d 
m ulti ple 
asce n di n g d ose, 
place b o -
c o ntr olle d, 
d o u ble bli n d 
( wit h P K 
sa m pli n g)
A d ult healt h y 
s u bjects
Si n gle d ose: 1 0 0, 4 0 0, 
1 0 0 0, 2 0 0 0, a n d 
2 8 0 0 m g
( C o h orts 1– 5)
Si n gle d ose
4 0 
( 3 0 acti ve/ 1 0 
place b o)
C o m plete
M ulti ple d ose: 3 0 0, 
6 0 0, a n d 9 0 0 m g 
( C o h orts 8– 1 0)
M ulti ple d ose × 
1 5 da ys
2 4
( 1 8 acti ve/ 6 place b o)
A d ult 
s u bjects wit h 
S C D
Si n gle d ose: 
1 0 0 0 m g
( C o h ort 7)
Si n gle d ose
8 
( 6 acti ve/ 2 place b o)
M ulti ple d ose: 5 0 0, 
7 0 0, a n d 1 0 0 0 m g 
( 5 0 0 m g t wice dail y) 
( C o h orts 1 1, 1 2, 1 4)
M ulti ple d ose × 2 8 
da ys
3 8
( 2 8 acti ve/
1 0 place b o)
M ulti ple d ose: 
6 0 0 m g
( C o h ort 1 5)
M ulti ple d ose × 2 8 
da ys
7
( 6 acti ve/ 1 place b o)
M ulti ple d ose: 
7 0 0 m g
( C o h ort 1 6)
M ulti ple d ose: 
9 0 0 m g
( C o h ort 1 7)
M ulti ple d ose × 9 0 
da ys
M ulti ple d ose × 9 0 
da ys
8
( 6 acti ve/ 2 place b o)
8
( 6 acti ve/ 2 place b o)
G B T 4 4 0 - 0 2 4
P hase 2a
1 Site/
U nite d 
Ki n g d o m
O pe n la bel, 
m ulti ple -d ose 
(e x pa nsi o n 
st u d y f or 
s u bjects w h o 
partici pate d i n 
G B T 4 4 0 -0 0 1 
C o h ort 1 5 a n d 
C o h ort 1 7)
A d ult 
s u bjects wit h 
S C D
9 0 0 m g 
6 m o nt hs ( T otal 
d urati o n i ncl u di n g 
e x p os ure fr o m 
G B T 4 4 0 -0 0 1) 
5
C o m plete
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 5
T a ble 1.
Cli nic al St u dies i n S C D wit h V o xel ot or ( C o nti n ue d)
St u d y 
N o./ P h ase
Sites/ 
L oc ati o n
St u d y 
T y pe
St u d y 
P o p ul ati o n
V o xel ot or D oses 
E v al u ate d
Tre at m e nt 
D ur ati o n
N o. of S u bjects
St at us of 
e nr oll me nt
G B T 4 4 0 -0 0 7 
P hase 2a
1 5 Sites/ 
U nite d 
States a n d 
Le ba n o n
O pe n -la bel, 
si n gle- a n d 
m ulti ple -d ose, 
P K, safet y, a n d 
treat me nt effect
Pe diatric 
s u bjects wit h 
S C D
Part A: 6 0 0 m g
Part B: 9 0 0 a n d 1 5 0 0 
m g 
Part C: 1 5 0 0 m g or 
1 5 0 0 m g e q ui vale nt
Part D: 1 5 0 0 m g 
e q ui vale nt
Part A: Si n gle D ose
Part B: M ulti ple d ose
U p t o 2 4 w ee ks 
Part C: M ulti ple d ose
U p t o 4 8 w ee ks 
( pe diatric p o p ulati o n 
a ge d 4 t o 1 7 years)
Part D: M ulti ple 
d ose
U p t o 4 8 w ee ks 
( pe diatric p o p ulati o n 
a ge d 9 m o nt hs t o 
< 4 years)
P art A:
-6 t o < 1 2 y ears: 6
-1 2 t o < 1 8 years: 7
C o m plete
P art B:
-1 2 t o < 1 8 years: 
2 5 e nr olle d at 9 0 0 m g
-1 5 e nr olle d at 1 5 0 0 
m g C o m plete 
Part C: 4 2 e nr olle d *
Part D: N ot starte d
O n g oi n g
G B T 4 4 0 -0 3 1 
P hase 3 ( H O P E 
St u d y)
1 0 0 I nter -
nati o nal 
sites
D o u ble -bli n d, 
ra n d o mize d, 
place b o -
c o ntr olle d
A d ults a n d 
a d olesce nts 
wit h S C D
v o xel ot or 9 0 0 m g or 
v o xel ot or 1 5 0 0 m g or 
place b o
U p t o 7 2 w ee ks
A p pr oxi m ately 3 7 0 -
4 3 5 pl a n ne d:
2 7 1 partici pa nts ha ve 
bee n ra n d o mize d a n d 
d ose d
C o m plete
P K = p har mac o ki netics; S C D = sic kle cell disease
* E nr oll me nt as of 0 5 N o ve m ber 2 0 1 9.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 6
1. 4. Descri pti o n a n d J ustific ati o n f or R o ute of A d mi nistr ati o n, D os a ge, D os a ge 
Re gi me n, a n d Tre at me nt Peri o d(s)
V o xel ot or is o nl y  a vaila ble i n oral f or m a n d is i nte n de d f or o nce daily a d mi nistrati o n. See 
Secti o n 5 f or a d diti o nal i nf or mati o n re gar di n g v o xel ot or. T he v o xel ot or d ose a d mi nistere d i n 
t his trial will be deter mi ne d fr o m st u dy G B T 4 4 0 -0 3 1. 
1. 5. Tri al C o n d uct
See Secti o n 1 1 f or details re gar di n g t he c o n d uct of t his trial. 
1. 6. Descri pti o n of t he P o p ul ati o n t o be St u die d
T his trial is li mite d t o partici pa nts wit h S C D w h o were e nr olle d a n d treate d i n G B T 4 4 0- 0 3 1. 
See Secti o n 4 f or a d diti o nal i nf or mati o n re gar di n g partici pa nts f or t his trial.
1. 7. R ati o n ale f or t his St u d y
T his o pe n la bel e xte nsi o n st u d y  is bei n g c o n d ucte d t o assess l o n g-ter m safet y a n d treat me nt 
effect of v o xel ot or b y pr o vi di n g partici pa nts fr o m t he G B T 4 4 0-0 3 1 st u d y  c o nti n ue d access t o 
treat me nt wit h v o xel ot or after t heir partici pati o n i n G B T 4 4 0- 0 3 1 a n d pri or t o t he pr o d uct 
p ote ntiall y  bei n g a vaila ble c o m merciall y. All partici pa nts e nr olle d i nt o t his st u d y will recei ve 
v o xel ot or.
2. T RI A L O B J E C TI V E S A N D P U R P O S E
T he o bjecti ve of t his o pe n -la bel e xte nsi o n ( O L E) st u d y is t o assess t he l o n g-ter m safet y a n d 
treat me nt effect of v o xel ot or i n partici pa nts w h o ha ve c o m plete d treat me nt i n st u d y 
G B T 4 4 0 -0 3 1, usi n g t he f oll o wi n g para meters:

Safet y  base d u p o n A Es, cli nical la b orat or y tests, p h ysical e xa mi nati o ns ( P E) 
a n d ot her cli nical meas ures.  

Fre q ue nc y  of sic kle cell disease-relate d c o m plicati o ns 

He m ol y tic a ne mia as meas ure d by he mat ol o gical la b orat or y  para meters (e g,
he m o gl o bi n, retic ul oc y tes a n d u nc o nj u gate d bilir u bi n).
3. I N V E S TI G A TI O N A L P L A N
3. 1. O ver all St u d y Desi g n
3. 1. 1. E n d p oi nts
3. 1. 1. 1. S afet y 
Safet y  e n d p oi nts i ncl u de A Es, cli nical la b orat or y tests, p h ysical e xa mi nati o ns a n d ot her 
cli nical meas ures.
3. 1. 1. 2. Sic kle Cell Dise ase ( S C D) -Rel ate d C o m plic ati o ns
Fre q ue nc y of S C D -relate d c o m plicati o ns of l o n g-ter m d osi n g wit h v o xel ot or.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 7
3. 1. 1. 3. Tre at me nt Effect
He m ol y tic a ne mia as meas ure d b y he mat ol o gical la b orat or y  para meters (e g, he m o gl o bi n, 
retic ul oc ytes a n d u nc o nj u gate d bilir u bi n).
3. 1. 2. Desi g n
T his o pe n la bel e xte nsi o n ( O L E), m ulti-ce nter st u d y will be c o n d ucte d at a p pr o xi matel y 1 0 0 
cli nical sites gl o ball y a n d will be a vaila ble t o eli gi ble partici pa nts fr o m st u d y G B T 4 4 0- 0 3 1.
T he st u d y  will e nr oll partici pa nts fr o m G B T 4 4 0 - 0 3 1 u n der a ny of t he f oll o wi n g c o n diti o ns:

Partici pa nt has c o m plete d 7 2 wee ks of treat me nt re gar dless of d ose selecti o n f or 
G B T 4 4 0 - 0 3 1

D ose selecti o n has occ urre d f or G B T 4 4 0 - 0 3 1 a n d partici pa nt is o n t he n o n-
selecte d d ose o n G B T 4 4 0-0 3 1

G B T 4 4 0 -0 3 1 st u d y  i nteri m data a nalys is a n d/ or st u d y m o dificati o ns ha ve 
occ urre d

G B T 4 4 0 -0 3 1 st u d y  has c o m plete d
3. 2. N u m ber of S u bjects
All partici pa nts (a p pr o xi matel y  4 3 5 or t he ma xi m u m n u m ber of partici pa nts i n G B T 4 4 0-0 3 1) 
w h o recei ve d treat me nt i n st u d y G B T 4 4 0- 0 3 1 a n d w h o meet t he eli gi bilit y  criteria f or t his 
st u d y m a y be e nr olle d.
3. 3. Tre at me nt Assi g n me nt
T his is a n o pe n -la bel trial; all partici pa nts will recei ve dail y v o xel ot or treat me nt.
3. 4. Criteri a f or St u d y Ter mi n ati o n
T he S p o ns or has t he ri g ht t o ter mi nate t his st u d y  at a n y ti me. Reas o ns f or ter mi nati n g t he 
st u d y m a y  i ncl u de, b ut are n ot li mite d t o, t he i nci de nce or se verity of A Es i n t his or ot her 
st u dies of v o xel ot or i n dicati n g a p ote ntial healt h hazar d t o partici pa nts. 
I n a ny i nsta nce of earl y ter mi nati o n of t he st u d y, t he S p o ns or will n otif y, i n writi n g, t he 
I n vesti gat ors, re g ulat or y a ut h orities a n d et hic c o m mittees ( E C), a n d will s pecif y t he reas o n(s) 
f or ter mi nati o n.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 8
4. S E L E C TI O N A N D WI T H D R A W A L O F S U B J E C T S
Eli gi bilit y  will be base d o n assess me nts pri or t o recei vi n g st u d y  dr u g o n Da y 1 i n t his st u d y. 
A partici pa nt will be c o nsi dere d e nr olle d u p o n t he si g ni n g of t he I C F a n d/ or si g ni n g t he 
asse nt (f or partici pa nts bet wee n 1 2 t o < 1 8 ye ars of a ge) f or t his st u d y . Inf or me d 
c o nse nt/asse nt m ust be pr o perl y e xec ute d pri or t o t he perf or ma nce of a n y pr ot oc ol -re q uire d 
assess me nt or pr oce d ure. 
4. 1. S u bject I ncl usi o n Criteri a
1.
Male or fe male st u d y pa rtici pa nts wit h S C D w h o partici pate d a n d recei ve d st u d y 
treat me nt i n G B T 4 4 0-0 3 1. 
N ote: Partici pa nts i n G B T 4 4 0- 0 3 1 w h o disc o nti n ue d st u d y  dr u g d ue t o a n A E, b ut 
w h o re mai ne d o n st u d y ma y  be eli gi ble f or treat me nt i n t his st u d y pr o vi de d t he A E 
d oes n ot p ose a ris k f or treat me nt wit h v o xel ot or .
2.
Fe males of c hil d -beari n g p ote ntial are re q uire d t o ha ve a ne gati ve uri ne pre g na nc y  
test pri or t o d osi n g o n Da y 1.
3.
Fe male partici pa nts of c hil d -beari n g p ote ntial m ust use hi g hl y effecti ve met h o ds of 
c o ntrace pti o n t o 3 0 da y s after t he last d ose of st u d y dr u g. Male partici pa nts m ust use 
barrier met h o ds of c o ntrace pti o n t o 3 0 da y s after t he last d ose of st u d y dr u g.
4.
Partici pa nt has pr o vi de d writte n i nf or me d c o nse nt or asse nt (t he I CF m ust be 
re vie we d a n d si g ne d by eac h parti ci pa nt; i n t he case of pe diatric partici pa nts, b ot h t he 
c o nse nt of t he partici pa nt’s le gal re prese ntati ve or le gal g uar dia n, a n d t he 
partici pa nt’s asse nt m ust be o btai ne d).
4. 2. S u bject E xcl usi o n Criteri a
1.
Fe male w h o is breast -fee di n g or pre g na nt.
2.
Partici pa nt wi t h dre w c o nse nt fr o m St u d y G B T 4 4 0- 0 3 1.
3.
Partici pa nt was l ost t o f oll o w- u p fr o m St u d y  G B T 4 4 0- 0 3 1.
4.
Partici pa nt re q uiri n g c hr o nic dial y sis.
5.
A n y  me dical, psyc h ol o gical, safet y, or be ha vi oral c o n diti o ns, w hic h, i n t he o pi ni o n of 
t he In vesti gat or, ma y  c o nf o u n d safet y i nter pretati o n, i nterfere wit h c o m plia nce, or 
precl u de i nf or me d c o nse nt.
4. 3. S u bject Wit h dr a w al Criteri a
Partici pa nts will be i nf or me d t hat t he y  are free 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 ny reas o n. If a partici pa nt wit h dra ws fr o m t his st u d y, t he date a n d reas o n f or wit h dra wal 
will be d oc u me nte d o n t he case re p ort f or m ( C R F). 
Partici pa nts ma y  be disc o nti n ue d fr o m st u d y treat me nt f or a n y of t he f oll o wi n g reas o ns:

A d verse e ve nt
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 1 9

Use of a pr o hi bite d t hera p y (Secti o n 5. 5. 3 )

Wit h dra wal of c o nse nt/asse nt

Discreti o n of t he I n vesti gat or

Partici pa nt is l ost t o f o ll o w- u p 

Partici pa nt is n o nc o m plia nt

Pre g na nc y
T he E n d of St u d y  ( E O S) visit s h o ul d be c o n d ucte d wit hi n 2 8-3 5 da y s after last d ose of st u d y 
dr u g f or partici pa nts w h o wit h dra w fr o m t he st u d y earl y.  
5. T R E A T M E N T O F S U B J E C T S
Partici pa nts w h o c o m plete 7 2 wee ks of treat me nt o n G B T 4 4 0- 0 3 1, re gar dless of a d ose 
selecti o n f or G B T 4 4 0-0 3 1, will recei ve v o xel ot or at t he hi g hest d ose (eit her 9 0 0 or 1 5 0 0 -m g ) 
dee me d safe f or c o nti n ue d assess me nt o n t he G B T 4 4 0 -0 3 1 st u d y  b y t he Data Safety 
M o nit ori n g B oar d ( D S M B).  
O nce a d ose is selecte d f or st u d y  G B T 4 4 0-0 3 1, all G B T 4 4 0 -0 3 1 partici pa nts o n t he n o n -
selecte d d ose will be eli gi ble t o e nr oll i nt o t his O L E st u d y at t he selecte d d ose. All 
partici pa nts alrea d y e nr olle d i n t his O L E st u d y  at t he ti me of t he d ose selecti o n will be 
a d mi nistere d t he selecte d d ose at t heir ne xt sc he d ule d assess me nt.
Partici pa nts ma y  be eli gi ble t o e nr oll i n t his O LE st u d y  pri or t o G B T 4 4 0-0 3 1 st u d y  
c o m pleti o n base d o n i nteri m data res ults a n d/ or s u bse q ue nt st u d y  m o dificati o ns o n G B T 4 4 0-
0 3 1. If t his occ ur s, sites will be n otifie d w hic h partici pa nts are eli gi ble. 
W he n st u d y  G B T 4 4 0-0 3 1 has c o m plete d, partici pa nts will be eli gi ble t o e nr oll i n t his st u d y .
If a partici pa nt was o n a re d uce d d ose of v o xel ot or d ue t o a n A E i n G B T 4 4 0-0 3 1 or o n t his 
st u d y pri or t o a d ose selecti o n o n G B T 4 4 0 -0 3 1, d osi n g i n t his st u d y  ma y be c o nti n ue d at t he 
re d uce d d ose if dee me d cli nicall y a p pr o priate by t he I n vesti gat or. T he ori gi nal d ose ma y  be 
res u me d if dee me d cli nicall y a p pr o priate by t he I n vesti gat or.
Partici pa nts ma y  recei ve st u d y dr u g as l o n g as t he y c o nti n ue t o recei ve cli nical be nefit w hic h 
o ut wei g hs ris k as deter mi ne d b y  t he I n vesti gat or a n d/ or u ntil t he partici pa nt has access t o  
v o xel ot or fr o m a n alter nati ve s o urce (i.e., c o m mercializati o n or t hr o u g h a ma na ge d access 
pr o gra m). 
T he E O S visit ca n occ ur a n y  ti me after partici pa nts o btai ns c o m mercial v o xel ot or f or 
partici pa nts w h o c o m plete st u d y  per pr ot oc ol. Partici pa nts s h o ul d re mai n o n st u d y dr u g u ntil 
E O S visit is c o m plete d.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 0
5. 1. St u d y Dr u g I nf or m ati o n
V o xel ot or is s ynt hetic s mall m olec ule beari n g t he c he mical na me 2-h y dr o x y - 6-(( 2-( 1-
is o pr o p yl- 1 H-p y raz ol- 5-yl ) pyri di n -3- yl ) met h o x y) be nzal de h yde. T he c he mical f or m ula is 
C 1 9 H 1 9 N 3 O 3 a n d t he m olec ular wei g ht is 3 3 7. 3 8.
V o xel ot or 3 0 0 m g or 5 0 0 m g ta blets c o ntai n G B T 4 4 0 dr u g s u bsta nce al o n g wit h se veral 
f or m ulati o n e xci pie nts. All t he e xci pie nts use d f or t he f or m ulati o n are c o m plia nt wit h 
E ur o pea n re g ulati o ns a n d are liste d i n t he F o o d a n d Dr u g A d mi nistrati o n ( F D A) I nacti ve 
I ngre die nts Data base (II D).
V o xel ot or ta blets will be s u p plie d t o cli nical sites i n hi g h de nsity p ol yet h yl e ne ( H D P E) 
b ottles wit h i n d ucti o n seale d p ol y pr o p y le ne ( P P) ca ps. A d diti o nal details are pr o vi de d i n t he 
P har mac y  Ma n ual.
All st u d y  me dicati o n will be st ore d at c o ntr olle d r o o m te m perat ure bet wee n 1 5° C to 2 5° C, i n 
t he st ora ge area of t he i n vesti gati o nal site p har mac y.
N o s pecial pr oce d ures f or t he safe ha n dli n g o n v o xel ot or are re q uire d. T he S p o ns or will be 
per mitte d u p o n re q uest t o a u dit t he s u p plies, st ora ge, dis pe nsi n g pr oce d ures a n d rec or ds. 
5. 2. St u d y Dr u g Dis pe ns ati o n
St u d y  Dr u g will be dis pe nse d at t he Da y 1 visit a n d e ver y 3 m o nt hs t hereafter. Partici pa nts 
will recei ve a 3-m o nt h ( 9 0 da y ) s u p pl y of st u d y dr u g at eac h dis pe nsati o n visit.
Partici pa nts s h o ul d be i nstr ucte d t o ta ke st u d y dr u g o nce dail y wit h water or ot her n o n-
alc o h olic be vera ge prefera bl y  at t he sa me ti me eac h da y. St u d y dr u g ma y be ta ke n wit h or 
wit h o ut f o o d. 
5. 3. Dr u g Acc o u nt a bilit y a n d Rete nti o n
I n acc or da nce wit h G o o d Cli nical Practice ( G C P), t he I n vesti gati o nal Site will acc o u nt f or all 
s u p plies of v o xel ot or. Details of recei pt, st ora ge, dis pe nsati o n, a n d ret ur n will be rec or de d.
T he I n vesti gat or m ust e ns ure t hat all dr u g s u p plies are ke pt i n a sec ure l oc ke d area wit h 
access li mite d t o t h ose a ut h orize d b y  t he I n vesti gat or.
T he I n vesti gat o r ( or desi g nee) will mai ntai n a n acc urate rec or d of t he recei pt of t he 
i n vesti gati o nal pr o d uct as s hi p pe d b y t he S p o ns or ( or desi g nee), i ncl u di n g, b ut n ot li mite d t o, 
t he date recei ve d, st ora ge c o n diti o ns/l ocati o n, l ot n u m ber, a m o u nt recei ve d, a n d t he 
dis p ositi o n of all i n vesti gati o nal pr o d uct. A c o p y of t he recei pt will be ret ur ne d t o t he 
S p o ns or w he n t he c o nte nts of t he i n vesti gati o nal pr o d uct s hi p me nt ha ve bee n verifie d.
C urre nt dis pe nsi n g rec or ds will als o be mai ntai ne d i ncl u di n g t he date a n d a m o u nt of 
i n vesti gati o nal pr o d uct dis pe nse d a n d t he partici pa nt recei vi n g t he dr u g. T his dr u g 
acc o u nta bilit y rec or d will be a vaila ble f or i ns pecti o n at a n y ti me.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 1
At t he c o m pleti o n of t he st u d y, t he ori gi nal dr u g acc o u nta bilit y  rec or d will be a vaila ble f or 
re vie w by t he S p o ns or u p o n re q uest.
All u n use d s u p plies of v o xel ot or will eit her be destr o y e d b y t he i n vesti gati o nal site or 
ret ur ne d t o t he S p o ns or i n acc or da nce wit h S p o ns or i nstr ucti o ns. 
A d diti o nal details are pr o vi de d i n t he P har mac y  Ma n ual.
5. 4. D ose M o dific ati o n
Partici pa nts s h o ul d a d here t o t he assi g ne d d ose. H o we ver, d ose m o dificati o n f or ma na ge me nt 
of a d verse e ve nts s h o ul d be c o nsi dere d as o utli ne d bel o w. G ui deli nes f or re d ucti o n, 
i nterr u pti o n, or per ma ne nt disc o nti n uati o n of st u d y dr u g are pr o vi de d bel o w i n Ta ble 2
(st u d y dr u g-relate d A Es) a n d Ta ble 3 (st u d y dr u g-relate d ras h).
All i nsta nces of st u d y dr u g m o dificati o n ( d ose re d ucti o n, i nterr u pti o n, or disc o nti n uati o n) are 
t o be ca pt ure d i n t he partici pa nts’ me dical rec or d a n d o n t he C R Fs. If t he c o n diti o ns/e ve nt 
lea di n g t o t he d ose m o dificati o n ha ve res ol ve d, t he ori gi nal d ose le vel m a y  be res u me d, 
u nless i n t he j u d g me nt of t he I n vesti gat or, t his ca n n ot be d o ne safel y .
If a partici pa nt e nr olle d i n t his st u d y is o n a re d uce d d ose d ue t o a n A E pri or t o d ose 
selecti o n o n G B T 4 4 0-0 3 1, d osi n g ma y  be c o nti n ue d at t he re d uce d d ose if dee me d cli nically 
a p pr o priate b y t he I n vesti gat or. 
T a ble 2.
D ose M o dific ati o n G ui deli nes f or St u d y Dr u g -Rel ate d A d verse E ve nts
D ose Re d ucti o n
E ve nt
Rec o m me n de d Acti o n
Gr a de 2 or hi g her A E t hat is ( 1) st u d y dr u g-
relate d i n t he o pi ni o n of t he I n vesti gat or A N D 
( 2) t hat precl u des c o nti n ue d d osi n g at t he 
c urre nt d ose le vel d ue t o safet y c o ncer n or lac k 
of t olera bilit y (i n t he I n vesti gat or’s j u d g me nt) 
St u d y dr u g : Ma y be re d uce d b y o ne ( 1) ta blet. 
If, i n t he o pi ni o n of t he I n vesti gat or, a Gra de 2 A E has 
res ol ve d t o ≤ Gra de 1, partici pa nt ma y res u me st u d y 
dr u g at t he ori gi nal d ose.
If, i n t he o pi ni o n of t he I n vesti gat or, t he A E p oses a 
si g nifica nt safet y c o ncer n s uc h t hat a d ose h ol d is 
c o nsi dere d, t he I n vesti gat or ma y c o nsi der a d ose 
i nterr u pti o n ( h ol d), Ma xi m u m d ose h ol d is 5 
c o nti n u o us da ys. If, i n t he o pi ni o n of t he I n vesti gat or, 
a l o n ger d ose h ol d is cli nicall y nee de d, t he Me dical 
M o nit or s h o ul d be c o ntacte d f or disc ussi o n.
A L T ≥3 x U L N if A L T W N L at b aseli ne O R 
> 3 X U L N A N D a ≥2 -f ol d i ncre ase a b o ve 
b aseli ne v al ues if ele v ate d A L T v al ues at 
b aseli ne
I n t he a bse nce of a d diti o nal si g ns of 
c o m pr o mise d li ver f u ncti o n s uc h as ele vate d 
St u d y dr u g : C o nfir m b y re peat testi n g wit hi n 4 8 t o 
7 2 h o urs if p ossi ble, t he n re peat li ver pa nel at least 
wee kl y u ntil A L T le vels i m pr o ves. 
A d diti o n al Acti o ns : If A L T le vels c o nti n ue t o 
i ncrease re d uce b y o ne ta blet a n d n otif y t he Me dical 
M o nit or
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 2
T a ble 2.
D ose M o dific ati o n G ui deli nes f or St u d y Dr u g -Rel ate d A d verse E ve nts
D ose Re d ucti o n
E ve nt
Rec o m me n de d Acti o n
P T, P T T, I N R, ele vate d c o nj u gate d bilir u bi n, 
ja u n dice, or he patic pai n.
A L T ≥5 × a n d < 8 × U L N (c o nfir me d b y re pe at 
testi n g wit hi n 4 8 t o 7 2 h o urs) I n t he a bse nce 
of a d diti o nal si g ns of c o m pr o mise d li ver 
f u ncti o n s uc h as ele vate d P T, P T T, ele vate d 
c o nj u gate d bilir u bi n, ja u n dice, or he patic pai n. 
St u d y dr u g : Re d uce d ose b y o ne ta blet.
A d diti o n al acti o ns : Re peat li ver pa nel test wit hi n 4 8 
t o 7 2 h o urs if p ossi ble a n d t he n at least wee kl y u ntil 
res ol uti o n t o < 5× U L N; if A L T test d oes n ot i m pr o ve 
wit hi n 2 wee ks of d ose re d ucti o n, t he Me dical 
M o nit or s h o ul d be n otifie d. If A L T c o nti n ues
t o 
i ncrease wit hi n 1 wee k after a d ose re d ucti o n, d ose 
s h o ul d be i nterr u pte d, a n d t he Me dical M o nit or 
s h o ul d be n otifie d.
D ose I nterr u pti o n ( H ol d)
E ve nt
Rec o m me n de d Acti o n
Gr a de 3 or hi g her A E t hat is ( 1) st u d y dr u g -
relate d i n t he o pi ni o n of t he I n vesti gat or A N D 
( 2) t hat precl u des c o nti n ue d d osi n g at t he 
c urre nt or at a re d uce d d ose le vel d ue t o safet y 
c o ncer n or lac k of t olera bilit y i n t he 
I nvesti gat or’s j u d g me nt
St u d y dr u g : H ol d d ose u ntil ≤Gra de 2, t he n res u me 
st u d y dr u g at ori gi nal d ose. If, i n t he o pi ni o n of t he 
I nvesti gat or, d osi n g s h o ul d be res u me d at a l o wer 
d ose, c o ntact t he Me dical M o nit or. If t he A E rec urs or 
w orse ns, re d uce d ose b y o ne ta blet. Ma xi m u m d ose 
h ol d is 5 c o nti n u o us da ys. If, i n t he o pi ni o n of t he 
I nvesti gat or, a l o n ger d ose h ol d is cli nicall y nee de d, 
t he Me dical M o nit or s h o ul d be c o ntacte d f or 
disc ussi o n.
T a ble 2 .
D ose M o dific ati o n G ui deli nes f or St u d y Dr u g -Rel ate d A d verse E ve nts 
( C o nti n ue d)
Dr u g Disc o nti n u ati o n
E ve nt
Rec o m me n de d Acti o n
Gr a de 3 or hi g her, st u d y dr u g -rel ate d S A E
St u d y dr u g : Disc o nti n ue st u d y dr u g. If t he 
I nvesti gat or c o nsi ders t hat t he partici pa nt w o ul d 
be nefit fr o m c o nti n ui n g treat me nt, t he Me dical 
M o nit or s h o ul d be c o ntacte d f or disc ussi o n.
Gr a de 3 or hi g her st u d y dr u g -rel ate d A E
t hat, at t he discreti o n of t he I n vesti gat or, 
warra nts disc o nti n uati o n of st u d y dr u g ( e g, has 
n ot i m pr o ve d or res ol ve d after d ose h ol d) 
St u d y dr u g : Disc o nti n ue st u d y dr u g. If t he 
I nvesti gat or c o nsi ders t hat t he partici pa nt w o ul d 
be nefit fr o m c o nti n ui n g treat me nt, t he Me dical 
M o nit or s h o ul d be c o ntacte d 
C o nsi der tre at me nt disc o nti n u ati o n if: 
St u d y dr u g : H ol d d ose, c o nfir m b y re peat testi n g 
wit hi n 4 8 t o 7 2 h o urs if p ossi ble, a n d assess f or 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 3
T a ble 2.
D ose M o dific ati o n G ui deli nes f or St u d y Dr u g -Rel ate d A d verse E ve nts 
( C o nti n ue d)
Dr u g Disc o nti n u ati o n
E ve nt
Rec o m me n de d Acti o n

A L T > 8 × U L N 

( 1) A L T > 3 x U L N or ( 2) A L T> 3 x 
A N D ≥2 -f ol d i ncre ase a b o ve b aseli ne 
v al ues if ele v ate d A L T v al ues at 
b aseli ne
wit h a d diti o nal si g ns of c o m pr o mise d 
li ver f u ncti o n s uc h as ele vate d P T, P T T, 
I N R, ele vate d c o nj u gate d bilir u bi n, 
ja u n dice, or he patic pai n, a p peara nce of 
fati g ue, na usea, v o miti n g, ri g ht u p per 
q ua dra nt pai n or te n der ness, fe ver, ras h, 
a n d/ or e osi n o p hilia 
p ote ntial re versi ble ca uses of li ver f u ncti o n test 
a b n or malities. C o ntact t he Me dical M o nit or f or 
disc ussi o n of st u d y dr u g disc o nti n uati o n.
T a ble 3 .
D ose M o dific ati o n G ui deli nes f or St u d y Dr u g -Rel ate d R as h
D ose Re d ucti o n
E ve nt
Rec o m me n de d Acti o n
Gr a de 1 or 2 st u d y dr u g -rel ate d r as h
M a n a ge me nt:
C o nsi der a nti hista mi nes, t o pical ster oi ds as 
cli nicall y i n dicate d.
St u d y dr u g : If ras h d oes n ot res ol ve or i m pr o ve t o Gra de 1 
wit hi n 4 da ys after oral a nti hista mi nes a n d/ or t o pical 
ster oi ds, t he d ose ma y be re d uce d b y o ne ( 1) ta blet. T he 
d ose ma y be re d uce d f urt her b y o ne ta blet if t he e ve nt d oes 
n ot res ol ve.
If i n t he o pi ni o n of t he I n vesti gat or, a Gra de 2 A E has 
res ol ve d t o ≤Gra de 1, partici pa nt ma y res u me st u d y dr u g at 
t he ori gi nal d ose.
D ose I nterr u pti o n ( H ol d)
E ve nt
Rec o m me n de d Acti o n
Gr a de 1 or 2 st u d y dr u g -rel ate d r as h 
t h at persists after d ose re d ucti o n
M a n a ge me nt:
C o nsi der a nti hista mi nes, t o pical ster oi ds as 
cli nicall y i n dicate d. C o nsi der a Der mat ol o g y C o ns ult if 
cli nicall y i n dicate d.
St u d y dr u g : If ras h d oes n ot res ol ve or i m pr o ve t o Gra de 1 
o n t he l o wer d ose, c o nsi der a d ose h ol d u ntil res ol uti o n or 
e ve nt ret ur ns t o Gra de 1 or Baseli ne. O nce ras h has res ol ve d 
or i m pr o ve d t o G ra de 1, d osi n g ma y be res u me d at t he 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 4
T a ble 3.
D ose M o dific ati o n G ui deli nes f or St u d y Dr u g -Rel ate d R as h
D ose Re d ucti o n
re d uce d le vel. Ma xi m u m d ose h ol d is 5 c o nti n u o us da ys. If, 
i n t he o pi ni o n of t he I n vesti gat or, a l o n ger d ose h ol d is 
cli nicall y nee de d, t he Me dical M o nit or s h o ul d be c o ntacte d 
f or disc ussi o n.
If, i n t he o pi ni o n of t he I n vesti gat or, a Gra de 2 A E has 
res ol ve d t o < Gra de 1, partici pa nt ma y res u me st u d y dr u g at 
t he ori gi nal d ose.
Dr u g Disc o nti n u ati o n
E ve nt
Rec o m me n de d Acti o n
Gr a de 3 or hi g her st u d y dr u g -rel ate d 
r as h
St u d y dr u g : Disc o nti n ue st u d y dr u g.
C o nsi der a Der mat ol o g y C o ns ult if cli nicall y i n dicate d. 
N otif y Me dical M o nit or. 
5. 5. C o nc o mit a nt Me dic ati o ns
A c o nc o mita nt me dicati o n is defi ne d as a n y prescri pti o n or o ver -t he-c o u nter pre parati o n, 
i ncl u din g vita mi ns a n d s u p ple me nts, as well as i n vesti gati o nal pr o d ucts ot her t ha n t h ose 
u n der st u d y  i n t his trial.
5. 5. 1. Pri or a n d C o nc o mit a nt Me dic ati o ns
E xce pt as n ote d bel o w, i n t he i nterests of partici pa nt safet y a n d acce pta ble sta n dar ds of 
me dical care, t he I n vesti gat or will be per mitte d t o prescri be treat me nt(s) at his/ her discreti o n. 
All a d mi nistere d c o nc o mita nt me dicati o ns fr o m si g ni n g t he I C F u ntil 2 8 da ys after t he 
partici pa nt’s last d ose of st u d y  dr u g m ust be rec or de d o n t he partici pa nts’ C R F ( me dicati o n, 
d ose, treat me nt d urati o n a n d i n dicati o n).
5. 5. 2. All o we d C o nc o mit a nt Me dic ati o ns
Per mitte d c o nc o mita nt me dicati o ns i ncl u de pe nicilli n, f olic aci d, a n d c o dei ne, w hic h are 
a m o n g t he c hr o nic me dicati o ns c o m m o nl y  ta ke n b y S C D partici pa nts.
H y dr o x y ure a ( H U), L -gl ut a mi ne t her a p y a n d criz a nliz u m a b, w here a v ail a ble, are 
all o we d. 
5. 5. 3. Pr o hi bite d Me dic ati o ns
Use of a n i n vesti gati o nal pr o d uct ot her t ha n t hat u n der st u d y i n t his trial, re gar dless of its 
i nte n de d use, is pr o hi bite d t hr o u g h o ut t he trial a n d f or t he 2 8 da ys after t he last d ose. 
V o xel ot or is a m o derate C Y P 3 A 4 i n hi bit or a n d s h o ul d n ot be c o- a d mi nistere d wit h se nsiti ve 
C Y P 3 A 4 s u bstrates wit h a narr o w t hera pe u tic i n de x. See Ta ble 4 f or e xa m ples.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 5
T a ble 4.
Se nsiti ve C Y P 3 A 4 S u bstr ates wit h N arr o w T her a pe utic R a n ge
Se nsiti ve C Y P 3 A 4 S u bstr ates wit h N arr o w T her a pe utic R a n ge
Alfe nta nil, sir oli m us, a n d tacr oli m us
Ple ase n ote t he f oll o wi n g: T his is n ot a n e x h a usti ve list.  C o u ntr y -s pecific lists m a y be use d if a v ail a ble.
Si nce C Y P 3 A 4 is a pri mar y  C Y P (c yt oc hr o me P 4 5 0) res p o nsi ble f or t he meta b olis m of 
v o xel ot or, c o nc o mita nt use of v o xel ot or a n d m o derate or str o n g i n d ucers of C Y P 3 A 4 is n ot 
all o we d (refer t o Ta ble 5 f or e xa m ples).
T a ble 5. 
E x a m ples of M o der ate a n d Str o n g C Y P I n d ucers
C Y P 3 A 4
E x a m ples
M o derate C Y P 3 A 4 I n d ucers
Ce n o ba mate, da brafe ni b , b ose nta n, efa vire nz, etra viri ne, 
l orlati ni b, pe xi darti ni b, p he n o bar bital, pri mi d o ne, a n d s ot orasi b
Str o n g C Y P 3 A 4 I n d ucers
A pal uta mi de, car ba maze pi ne, e nzal uta mi de, i v osi de ni b, 
l u macaft or, mit ota ne, p he n yt oi n, rifa m pi n, a n d St. J o h n’s w ort
Ple ase n ote t he f oll o wi n g: T his is n ot a n e x h a usti ve list. C o u ntr y -s pecific lists m a y be use d if a v ail a ble.
F or a n u p date d list, refer t o t he f oll o wi n g li n k: 
htt ps:// w w w.f da. g o v/ Dr u gs/ De vel o p me nt A p pr o val Pr ocess/ De vel o p me nt Res o urces/ Dr u gI nteracti o ns La beli n g
/ uc m 0 9 3 6 6 4. ht m #ta ble 3-3 . (last accesse d 3 0 Marc h 2 0 2 3).
Me dicati o ns
liste d i n Ta ble 6 are als o pr o hi bite d. 
T a ble 6 .
A d diti o n al Pr o hi bite d Me dic ati o ns
Pr o hi bite d Me dic ati o ns
Cisa pri de
T his list of dr u gs pr o hi bite d f or p ote ntial D DI c o ncer ns wit h t he I M P ma y  be re vise d d uri n g 
t he c o urse of t he st u d y wit h writte n n otificati o n fr o m t he s p o ns or t o i ncl u de or e xcl u de 
s pecific dr u gs or dr u g cate g ories f or vari o us reas o ns (e g, e mer gi n g D DI results f or t he I M P, 
a vaila bilit y of ne w i nf or mati o n i n literat ure o n t he D DI p ote ntial of ot her dr u gs) if t he o verall 
be nefit/ris k assess me nt is n ot i m pacte d or if t he c ha n ges d o n ot si g nifica ntl y i m pact t he 
safety of partici pa nts or t he scie ntific val ue of t he trial.
5. 5. 4. M a n a ge me nt of O ver d ose
Base d o n t he mec ha nis m of acti o n of v o xel ot or, a n o ver d ose mi g ht decrease O 2 deli ver y  t o 
tiss ues. Tra nsf usi o n , e xc ha n ge tra nsf usi o n, a n d/ or h yper baric O 2 t hera py m a y be 
a d mi nistere d i n t he e ve nt of a me dical e mer ge nc y  d ue t o a s us pecte d v o xel ot or o ver d ose. 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 6
5. 6. Fertilit y/ C o ntr ace pti ve Re q uire me nts
T here is n o i nf or mati o n a b o ut effects t hat v o xel ot or c o ul d ha ve o n t he de vel o p me nt of t he 
fet us i n h u ma ns. T heref ore, all fe male partici pa nts of c hil d-beari n g p ote ntial ( p ost me narc he) 
s h o ul d a v oi d pre g na nc y, a n d all acti ve male partici pa nts s h o ul d a v oi d fat heri n g a c hil d. 
Hi g hl y effecti ve mea ns of c o ntrace pti o n are liste d bel o w i n Secti o n 5. 6. 4.
5. 6. 1. I nstr ucti o ns f or Fe m ale P artici p a nts of C hil d-Be ari n g P ote nti al
F or fe male partici pa nts of c hil d -beari n g p ote ntial, pre g na nc y  s h o ul d be a v oi de d b y eit her 
a bsti ne nce fr o m se x/se x ual i nterc o urse or t he use of hi g hly effecti ve mea ns of c o ntrace pti o n 
f or t he d urati o n of t he st u d y, a n d f or a t otal peri o d of 3 0 da ys after t he partici pa nt has ta ke n 
her last d ose of v o xel ot or. Pre g na nc y  re p orti n g re q uire me nts are o utli ne d i n Secti o n 7. 2. 4 .
5. 6. 2. Fe m ale P artici p a nts of N o n -C hil d -Be ari n g P ote nti al
Fe male partici pa nts of n o n -c hil d- beari n g p ote ntial are defi ne d as: pre-me narc he, bilateral 
o o p h orect o m y / h ysterect o m y/ p ost- me n o pa usal fe males bei n g a me n orr h oeic f or greater t ha n 
2 ye ars wit h a n a p pr o priate cli nical pr ofile, e g, a ge a p pr o priate, hist or y of vas o m ot or 
s ym pt o ms. 
5. 6. 3. I nstr ucti o ns f or M ale P artici p a nts
It is i m p orta nt t hat t he part ners of male partici pa nts d o n ot bec o me pre g na nt d uri n g t he st u dy 
a n d f or a t otal peri o d of 3 0 da y s after t he male partici pa nt has ta ke n t heir last d ose of 
v o xel ot or. 
As a preca uti o n, all male partici pa nts s h o ul d a v oi d fat heri n g a c hil d b y  eit her a bsti ne nce or 
t he use of barrier met h o ds of c o ntrace pti o n. As t here is n o i nf or mati o n f or v o xel ot or bei n g 
secrete d i n t he ejac ulate, male partici pa nts (i ncl u di n g me n w h o ha ve ha d vasect o mies) w h ose 
part ners are c urre ntl y  pre g na nt s h o ul d use barrier met h o ds f or t he d urati o n of t he st u d y a n d 
f or 3 0 da ys after t he last d ose of v o xel ot or. 
5. 6. 4. Acce pt a ble F or ms of C o ntr ace pti o n 
Hi g hl y effecti ve met h o ds of birt h c o ntr ol are defi ne d as t h ose w hic h res ult i n a l o w fail ure 
rate (i.e., less t ha n 1 % per year) w he n use d c o nsiste ntl y a n d c orrectly. Hi g hl y effecti ve 
met h o ds of birt h c o ntr ol are as f oll o ws:

C o m bi ne d (estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n 
ass ociate d wit h i n hi b iti o n of o v ulati o n:

Oral

I ntra va gi nal

Tra ns der mal

Pr o gest o ge n - o nly h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n:

Oral
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 7

I njecta ble

I m pla nta ble

H or m o nal c o ntrace pti o n m ust be s u p ple me nte d wit h a barrier met h o d ( prefera bl y 
male c o n d o m)

I ntra uteri ne de vice (I U D)

I ntra uteri ne h or m o ne-releasi n g sys te m (I U S)

Bilateral t u bal occl usi o n

Se x ual a bsti ne nce: Se x ual a bsti ne nce is c o nsi dere d a hi g hl y effecti ve met h o d o nl y  
if t he partici pa nt is refrai ni n g fr o m heter ose x ual i nterc o urse d uri n g t he e ntire 
per i o d of ris k ass ociate d wit h t he st u d y treat me nts. T he relia bilit y of se x ual 
a bsti ne nce nee ds t o be e val uate d i n relati o n t o t he d urati o n of t he cli nical trial a n d 
t he preferre d a n d us ual lifest yle of t he partici pa nt.
F or male partici pa nts wit h fe male part n ers ca pa ble of re pr o d ucti o n: barrier met h o ds of 
c o ntrace pti o n: c o n d o m or occl usi ve ca p ( dia p hra g m or cer vical/ va ult ca ps) wit h s per mici dal 
f oa m/gel /fil m/crea m/s u p p osit or y. T he use of barrier c o ntrace pti ves s h o ul d al wa ys be 
s u p ple me nte d wit h t he use of a s per mici de.
5. 7. Tre at me nt C o m pli a nce
Treat me nt c o m plia nce will be base d o n c o m paris o n of t he dis pe nse d vers us ret ur ne d st u d y 
dr u g. 
5. 8. R a n d o miz ati o n a n d Bli n di n g
T his is a n o n -ra n d o mize d, o pe n-la bel st u dy of v o xel ot or. 
6. A S S E S S M E N T O F T R E A T M E N T E F F E C T  
T he d ura bili t y of t he re d ucti o n of he m ol ysis will be assesse d by he mat ol o gical para meters. 
He mat ol o g y  assess me nts f or t his trial are descri be d i n Secti o n 7. 1. 5. 1 .
6. 1. He m ol ytic A ne mi a
H b a n d he m ol ys is meas ures t hat will be s u m marize d via descri pti ve statistics i ncl u de mea n 
c ha n ge fr o m Baseli ne i n he m o gl o bi n, % retic ul oc ytes, a n d u nc o nj u gate d bilir u bi n. 
U nc o nj u gate d bilir u bi n is a direct meta b olic pr o d uct of H b deri ve d fr o m e xtra vasc ular
cleara nce ( C L) of R B Cs ( 8 5 % of u nc o nj u gate d bilir u bi n deri ves fr o m H b) a n d has bee n 
s h o w n t o c orrelate wit h R B C lifes pa n i n S C D. T he % retic ul oc yte c o u nt is t he he m ol ysis 
meas ure t hat is m ost r o b ustl y  c orrelate d t o R B C lifes pa n a n d reflects a p h ysi ol o gic b o ne 
marr o w res p o nse t o decrease d R B C destr ucti o n ( He b bel, 2 0 1 1 ). 
T here will be t w o baseli ne val ues use d t o descri be d ura bilit y  of H b a n d he m ol ysis res p o nses: 
( 1) Baseli ne deri ve d fr o m t he pre- d ose he mat ol o g y  meas ure me nts o btai ne d d uri n g t he 
G B T 4 4 0 -0 3 1 st u d y  a n d ( 2) he mat ol o g y meas ure me nts o btai ne d via pre-d ose o n Da y  1 i n t his 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 8
st u d y. C ha n ge fr o m baseli ne, a n d perce nt c ha n ge fr o m baseli ne f or t he t w o af ore me nti o ne d 
baseli ne val ues will be c o m p ute d t o deter mi ne tre n ds o ver t he d urati o n of treat me nt.
7. A S S E S S M E N T O F S A F E T Y
7. 1. S afet y P ar a meters
Partici pa nt safet y a n d t olera bilit y will be m o nit ore d d uri n g t he st u d y usi n g sta n dar d 
meas ures , i ncl u di n g p h ysical e xa mi nati o ns, vital si g ns (i ncl u di n g bl o o d press ure [ B P]), 
safety la b orat or y  tests, c o nc o mita nt me dicati o n usa ge a n d A E m o nit ori n g. Assess me nts will 
be perf or me d at defi ne d ti mes d uri n g t he st u d y as i n dicate d i n t he Sc he d ule of Assess me nts 
(A p pe n di x 1 ). 
T here are a d diti o nal assess me nts ( Wee k 4 a n d Wee k 8) d uri n g t he first 8 wee ks of t his st u d y  
f or partici pa nts w h o tra nsiti o n fr o m G B T 4 4 0-0 3 1 a n d meet t he f oll o wi n g criteria :

If t he d ose f or t his trial is 1 5 0 0 m g, a n d t he partici pa nt was ra n d o mize d t o eit her 
v o xel ot or 9 0 0 m g or place b o i n G B T 4 4 0 - 0 3 1. 

If t he d ose is 9 0 0 m g, a n d t he partici pa nt was ra n d o mize d t o place b o i n G B T 4 4 0-
0 3 1 st u d y .

If a partici pa nt recei ve d less t ha n 1 2 wee ks of treat me nt i n G B T 44 0- 0 3 1. 
M ore fre q ue nt assess me nts, as per I n vesti gat or or healt h care pr o vi der j u d ge me nt, ma y  be 
c o n d ucte d if nee de d f or ma na ge me nt of A Es or per sta n dar d of care at eac h site.
7. 1. 1. De m o gr a p hic/ Me dic al Hist or y
Me dical hist or y  will be rec or de d at t he ti me of t he p h ysical e xa mi nati o n o n Da y 1. T he 
me dical hist or y  will i ncl u de i nf or mati o n ca pt ure d u n der St u d y G B T 4 4 0-0 3 1 a n d ne w e ve nts 
t hat occ urre d si nce partici pati n g i n G B T 4 4 0-0 3 1 as cli nicall y  a p pr o priate. O n g oi ng A Es i n 
G B T 4 4 0 -0 3 1 will be rec or de d as ne w Me dical Hist or y  f or t his trial.
7. 1. 2. Vit al Si g ns
Vital si g ns ( heart rate [ H R], B P) will be c ollecte d after a partici pa nt has reste d f or at least 
5 mi n utes i n t he seate d or s u pi ne p ositi o n. A re peate d meas ure me nt of H R a n d B P will be 
ta ke n if t he first rea di n g is o utsi de t he n or mal ra n ge a n d dee me d cli nically s i g nifica nt.
7. 1. 3. P h ysic al E x a mi n ati o n
A n a b bre viate d P E a n d a s y m pt o m directe d e xa mi nati o n will be c o m plete d at all visits. 
A n a b bre viate d P E will i ncl u de at mi ni m u m ge neral a p peara nce, e xa mi nati o n of e y es, s ki n, 
car di o vasc ular a n d res pirat or y sys te ms, a n d a n a b d o mi nal e xa mi nati o n.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 2 9
7. 1. 4. Electr oc ar di o gr a m ( E C G)
E C Gs ( 1 2 -lea d) will be perf or me d f or partici pa nts fr o m G B T 4 4 0-0 3 1 w h o tra nsiti o ne d i nt o 
t his st u d y a n d recei ve d:

V o xel ot or at a d ose l o wer t ha n t he selecte d d ose ( e g, 9 0 0 m g f or t his trial)

Place b o 
E C Gs will be perf or me d after a partici pa nt has reste d f or at least 5 mi n utes i n t he seate d or 
s u pi ne p ositi o n . E C Gs ma y be o mitte d pe n di n g a re vie w of E C G data fr o m G B T 4 4 0-0 3 1 or 
E C G a nal ys es fr o m ot her cli nical st u dies t hat i n dicate E C Gs d o n ot nee d t o be c ollecte d i n 
t his trial. In t his case, n o st u d y -s pecific E C Gs w o ul d be re q uire d, b ut s h o ul d still be 
perf or me d as per sta n dar d of care.
A nal y sis fr o m G B T 4 4 0 -0 1 1 5, a de dic ate d T Q T st u d y i n healt h y s u bjects, i n dicate d t hat 
v o xel ot or ha d n o cli nicall y  si g nifica nt E C G fi n di n gs or n o effect o n t he Q T i nter val; 
t heref ore, E C G c ollecti o n i n t his trial is n o l o n ger re q uire d as of 2 0 A u g 2 0 1 9.
7. 1. 5. L a b or at or y Assess me nts
Ce ntral la b orat or y assess me nts will be perf or me d f or partici pa nts e nr olle d i n t he U nite d 
States a n d E ur o pe. 
L ocal la b orat or y  assess me nts will be perf or me d b y eac h site’s l ocal la b orat or y f or 
partici pa nts e nr olle d o utsi de of t he U nite d States or E ur o pe. 
T he la b orat or y  para meters liste d i n t he secti o ns bel o w will be assesse d. A d diti o nal la b orat or y  
assess me nts ma y be c ollecte d as i n dicate d per sta n dar d of care f or cli nical ma na ge me nt.
F or ad olesce nt partici pa nts, t he t otal v ol u me of bl o o d c ollecte d f or will n ot e xcee d t he
rec o m me nde d bl o o d sa m ple v ol u me li mits o utli ne d i n 2 0 1 0 W H O G ui deli nes. F or t his st u d y ,
1 2 y ears of a ge is t he yo u n gest a ge t o be e nr olle d, t h us t otal bl o o d v ol u me c ollecti o n will n ot 
e xcee d 2. 4 m L/ k g i n a gi ve n 4 wee k peri o d, f or a n y a d olesce nt e nr olle d i n t he st u d y.
7. 1. 5. 1. He m at ol o g y ( D a y 1 t hr o u g h Wee k 4 8)
He mat ol o g y  para meters f or t his trial are:

R B C 

he mat ocrit ( Hct) 

H b

platelets

w hite bl o o d cell ( W B C) 

% retic ul oc y tes

a bs ol ute retic ul oc ytes
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 0

R B C distri b uti o n wi dt h ( R D W)

Mea n c or p usc ular v ol u me ( M C V)

Mea n c o r p usc ular he m o gl o bi n c o nce ntrati o n ( M C H C)
7. 1. 5. 2. Bl o o d C he mistr y ( D a y 1 t hr o u g h Wee k 4 8)
Ser u m c he mistr y para meters are: 

ala ni ne a mi n otra nsferase ( A L T)

al kali ne p h os p hatase ( A L K)

as partate a mi n otra nsferase ( A S T)

bicar b o nate,

bl o o d urea nitr o ge n ( B U N) 

creati ni ne

lactate de hy d r o ge nase ( L D H)

S o di u m

P otassi u m

Bilir u bi n (t otal, direct, a n d i n direct)
Assess me nt of he mat ol o g y  a n d ser u m c he mistr y after Wee k 4 8 b ut s h o ul d be perf or me d per 
sta n dar d of care.
After Wee k 4 8, l ocal la b orat or y assess me nts f or H b a n d meas ures of he m ol ysis will be 
perf or me d b y  eac h site’s l ocal la b orat or y f or partici pa nts e nr olle d o utsi de of t he U nite d 
States a n d E ur o pe. ( E ver y 2 4 wee ks)

He m o gl o bi n

% retic ul oc y tes

a bs ol ute retic ul oc ytes

Bilir u bi n (t otal, direct, a n d i n direct)
7. 1. 5. 3. E x pl or at or y Me as ures Rel ate d t o S C D P at h o p h ysi ol o g y ( D a y 1, Wee ks 1 2, 2 4, 
a n d 4 8)
i ncl u de d as e x pl orat or y meas ures
f u ncti o n.  
da ma ge is a pr o gressi ve c o m plicati o n of S C D t hat be gi ns i n c hil d h o o d a n d 
ma y  pr o gress
. Assess me nts will be perf or me d o nly f or partici pa nts e nr olle d i n 
t he U nite d States a n d E ur o pe. 


0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)
C CI
C CI
C CI
C CI
C CI

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 1
7. 1. 5. 4. Pre g n a nc y Test ( All visits)
Fe male st u d y pa rtici pa nts w h o ha ve n ot e x perie nce d me narc he will n ot u n der g o pre g na nc y 
testi n g. S h o ul d a fe male partici pa nt e x perie nce me narc he d uri n g t he c o urse of t he st u d y , t he 
partici pa nt will be c o nsi dere d a fe male of c hil d beari n g p ote ntial a n d will u n der g o pre g na nc y 
testi n g as per t he Sc he d ule of Assess me nts. 
Fe male st u d y partici pa nts of c hil d beari n g p ote ntial will ha ve uri ne pre g na nc y tests at all 
visits. Fe male st u d y  partici pa nts wit h a p ositi ve pre g na nc y test at Da y 1 will n ot be eli gi ble 
t o partici pate i n t he st u d y. 
If a uri ne pre g na nc y test is p ositi ve, t he res ult m ust be c o nfir me d per l ocal sta n dar d of care 
(e g, ultras o u n d or ser u m pre g na nc y  test). Fe male partici pa nts of c hil d-beari n g p ote ntial 
s h o ul d be re mi n de d t o a v oi d pre g na nc y, a n d all acti ve male partici pa nts s h o ul d be re mi n de d 
t o a v oi d fat heri n g a c hil d. T his disc ussi o n s h o ul d be d oc u me nte d i n t he partici pa nt’s me dical 
rec or d. 
7. 1. 6. S C D -Rel ate d C o m plic ati o ns
7. 1. 6. 1. V as o -Occl usi ve Crisis ( V O C)
V O C m ust be d oc u me nte d i n t he partici pa nt’s me dical rec or d t hat t he parti ci pa nt was see n 
b y , or i n c o ntact wit h t he In vesti gat or or healt h care pr o vi der. T he e ve nt ma y  ta ke place i n a 
me dical setti n g ( h os pital, cli nic, e mer ge nc y  r o o m) or at h o me.   
Ac ute c hest s y n dr o me ( A C S) is defi ne d as a n ac ute ill ness c haracterize d b y fe ve r a n d/ or 
res pirat or y sy m pt o ms , acc o m pa nie d by a ne w p ul m o nar y i nfiltrate o n a c hest X -ra y.
V O C d uri n g t he treat me nt peri o d is defi ne d as:
A c o m p osite of ac ute pai nf ul crisis or A C S, a n d i ncl u des t he f oll o wi n g:

M o derate t o se vere pai n lasti n g at least 2 h o u rs

N o e x pla nati o n ot her t ha n V O C

Re q uires oral or pare nteral o pi oi ds, ket or olac, or ot her a nal gesics prescri be d 
or directe d b y a healt hcare pr ofessi o nal 

Ma y  i ncl u de e pis o des of A C S
V O C e ve nts a n d ass ociate d t hera pies will be s u m marize d via descri pti ve statistics. T hese 
e n d p oi nts i ncl u de:

Rate of V O C d uri n g treat me nt wit h v o xel ot or

Rate of V O C h os pitalizati o n d uri n g treat me nt wit h v o xel ot or

Rate of R B C tra nsf usi o n d uri n g treat me nt wit h v o xel ot o r

Rate of o pi oi d use d uri n g treat me nt wit h v o xel ot or
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 2
7. 1. 7. Ot her S C D -rel ate d C o m plic ati o ns
S C D -relate d c o m plicati o ns will be c ollecte d a n d assesse d o ver t he d urati o n of t he st u d y.
7. 2. A d verse a n d Seri o us A d verse E ve nts
Safet y  assess me nts will c o nsist of rec or di n g all A Es a n d S A Es, pr ot oc ol-s pecifie d 
he mat ol o g y  a n d cli nical c he mistr y varia bles, cli nical e xa mi nati o n fi n di n gs, meas ure me nt of 
pr ot oc ol -s pecifie d vital si g ns, a n d t he res ults fr o m ot her pr ot oc ol-s pecifie d tests t hat are 
dee me d critical t o t he safet y  e val uati o n of v o xel ot or.
All A Es will be rec or de d fr o m t he ti me t he st u d y  partici pa nt si g ns t he I CF u ntil at least 2 8 
da y s after last d ose of st u d y dr u g or E O S visit ( per A p pe n di x 1). T he deter mi nati o n, 
e val uati o n, re p orti n g, a n d f oll o w-u p of A Es will be perf or me d as o utli ne d i n t his secti o n. At 
eac h visit, t he st u d y partici pa nt will be as ke d a b o ut a n y ne w or o n g oi n g A E si nce t he 
pre vi o us visit. Assess me nts of A Es will occ ur at eac h st u d y visit. 
Cli nicall y  si g nifica nt c ha n ges fr o m st u d y baseli ne i n p h ysical e xa mi nati o n fi n di n gs, wei g ht, 
vital si g ns, a n d cli nical la b orat or y para meters, will be rec or de d as A Es or S A Es, as 
a p pr o priate.
7. 2. 1. A d verse E ve nts
7. 2. 1. 1. Defi niti o n of A d verse E ve nts
A n A E is defi ne d as a n y u nt o war d me dical o cc urre nce ass ociate d wit h t he use of a dr u g i n 
h u ma ns , w het her or n ot c o nsi dere d dr u g relate d. A n A E ca n t heref ore be a n y u nfa v ora ble a n d 
u ni nte n de d si g n, s y m pt o m, or disease te m p orall y  ass ociate d wit h t he use of a n i n vesti gati o nal 
pr o d uct, w het her or n ot t h o u g ht t o be relate d t o t he i n vesti gati o nal pr o d uct. A n A E ma y als o 
c o nstit ute c o m plicati o ns occ urri n g as a res ult of pr ot oc ol -ma n date d i nter ve nti o ns ( e g, 
i n vasi ve pr oce d ures s uc h as bi o psies), i ncl u di n g t he peri o d pri or t o recei vi n g t he first d ose of 
t he st u d y dr u g (e g, me dicati o n was h o ut, bi o psies). I n a d diti o n t o ne w e ve nts, a n y i ncrease i n 
t he se verity or fre q ue nc y of a pre -e xisti n g c o n diti o n t hat occ urs after t he partici pa nt si g ns t he 
I CF is c o nsi dere d a n A E. T his i ncl u des a n y  si de effect, i nj ur y, t oxicit y , or se nsiti vit y 
reacti o n. 
A s us pecte d a d verse reacti o n is a n y  A E f or w hic h t here is a reas o na ble p ossi bilit y t hat t he 
dr u g ca use d t he A E. F or t he p ur p oses of e x pe dite d safet y re p orti n g, “ Reas o na ble p ossi bilit y ” 
mea ns t here is e vi de nce t o s u g gest a ca usal relati o ns hi p bet wee n t he dr u g a n d t he A E. 
S us pecte d a d verse reacti o n i m plies a lesser de gree of certai nt y a b o ut ca usalit y  t ha n a d verse 
reacti o n, w hic h mea ns a n y A E ca use d by a dr u g. 
Life -t hreate ni n g A E or life-t hreate ni n g s us pecte d a d verse reacti o n is a n A E or s us pecte d 
a d verse reacti o n t hat, i n t he vie w of eit her t he i n vesti gat or or Pfizer, places t he st u d y  
partici pa nt 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 vere f or m, mig ht ha ve ca use d deat h. 
A n A E or s us pecte d a d verse reacti o n is c o nsi dere d “ u ne x pecte d” if it is n ot liste d i n t he 
c urre nt I B or is n ot liste d at t he s pecificity or se verit y  t hat has bee n o bser ve d. 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 3
A n S A E or seri o us s us pecte d a d verse reacti o n is a n A E or s us pecte d a d verse reacti o n t hat at 
a n y d ose, i n t he vie w of t he eit her t he i n vesti gat or or Pfizer, res ults i n a n y of t he f oll o wi n g 
o utc o mes: 

Deat h

A life -t hreate ni n g A E

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

Persiste nt or si g nifica nt i nca pacit y  or disa bilit y (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)

A c o n ge nital a n o mal y/ birt h defect

I m p orta nt me dical e ve nts (I M E) t hat ma y n ot res ult i n deat h, be i m me diatel y life-
t hreate ni n g, or re q uire h os pitalizati o n ma y be c o nsi dere d seri o us w he n base d 
u p o n me dical j u d ge me nt, t he y  ma y je o par dize t he st u d y partici pa nt 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 i n 
t his defi niti o n
N O T E: H os pitalizati o n pla n ne d pri or t o st u d y  e nr oll me nt (e g, f or electi ve s ur geries) are n ot 
c o nsi dere d S A Es. H os pitalizati o ns t hat occ ur f or pre- e xisti n g c o n diti o ns t hat are sc he d ule d 
after st u d y e nr ol me nt are c o nsi dere d S A Es. 
T he I n vesti gat or will assess eac h A E f or seri o us ness, se verit y, a n d relati o ns hi p t o 
i n vesti gati o nal pr o d uct.
7. 2. 1. 2. Se verit y of A d verse E ve nts
W he ne ver p ossi ble, t he se verit y of all A Es will be gra de d usi n g t he Nati o nal Ca ncer 
I nstit ute’s C o m m o n Ter mi n ol o g y  Criteria f or A d verse E ve nts ( N CI C T C A E), Versi o n 4. 0 3. 
F or A Es n ot a de q u atel y a d dresse d i n t he N CI C T C A E Versi o n 4. 0 3, t he f oll o wi n g criteria 
s h o ul d be use d (Ta ble 7 ).
T a ble 7.  
Gr a di n g f or A d verse E ve nts N ot C o vere d i n t he N CI C T C A E
Se verit y
Descri pti o n
Gra de 1 – Mil d
As y m pt o matic or mil d s y m pt o ms; cli nical or 
dia g n ostic o bser vati o ns o nl y; i nter ve nti o n n ot 
i n dicate d
Gra de 2 – M o derate
Mi ni mal, l ocal or n o n -i n vasi ve i nter ve nti o n 
i n dicate d; li mite d a ge a p pr o priate i nstr u me ntal 
acti vities of dail y li vi n g ( A D L)
Gra de 3 – Se vere
Me dicall y si g nifica nt b ut n ot i m me diatel y life 
t hreate ni n g; h os pitalizati o n or pr ol o n gati o n of 
h os pitalizati o n i n dicate d; disa bli n g; li miti n g 
self-care A D L.
Gra de 4 – Life t hreate ni n g
Life t hreate ni n g c o nse q ue nces; ur ge nt 
i nter ve nti o n i n dicate d
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 4
T a ble 7.  
Gr a di n g f or A d verse E ve nts N ot C o vere d i n t he N CI C T C A E
Se verit y
Descri pti o n
Gra de 5 – Fatal
Deat h
A b bre viati o ns: N CI C T C A E = Nati o nal Ca ncer I nstit ute C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts.
T o ma ke s ure t here is n o c o nf usi o n or mis u n dersta n di n g bet wee n t he ter ms “seri o us” a n d 
“se vere”, w hic h a n ot s y n o n y m o us, t he f oll o wi n g n ote of clarificati o n is pr o vi de d. T he ter m 
“se vere” is ofte n use d t o descri be t he i nte nsit y (se verit y) of a s pecific e ve nt (i.e. mil d, 
m o derate, or se vere); t he e ve nt itself, h o we ver , ma y be of relati vel y mi n or me dical 
si g nifica nce (e g, se vere hea dac he). T his is n ot t he sa me as “seri o us” w hic h is base d o n t he 
st u d y partici pa nt / e ve nt o utc o me or acti o n criteria ass ociate d wit h e ve nts t hat p ost a t hreat t o 
a partici pa nt’s life or f u nct i o ni n g. Seri o us ness ( n ot se verit y) ser ves as a g ui de f or defi ni n g 
re g ulat or y re p orti n g o bli gati o ns. 
7. 2. 1. 3. Rel ati o ns hi p t o I n vesti g ati o n al Pr o d uct
T he relati o ns hi p of a n A E t o t he i n vesti gati o nal pr o d uct s h o ul d be deter mi ne d b y  t he 
I n vesti gat or acc or di n g t o t he f oll o wi n g defi niti o ns:

N O T R E L A T E D: E vi de nce e xists t hat t he A E has a n eti ol o g y  ot her t ha n t he st u d y 
dr u g a n d/ or t he te m p oral relati o ns hi p of t he A E/ S A E t o t he i n vesti gati o nal 
pr o d uct a d mi nistrati o n ma kes t he relati o ns hi p u nli kel y . If a n S A E is n ot 
c o nsi dere d relate d t o st u d y dr u g, t he n a n alter nati ve e x pla nati o n s h o ul d be 
pr o vi de d.

R E L A T E D: A te m p oral relati o ns hi p e xists bet wee n t he e ve nt o nset a n d t he 
a d mi nistrati o n of t he st u d y dr u g ma kes a ca usal relati o ns hi p p ossi ble or pr o ba bl y. 
It ca n n ot be rea dily e x plai ne d b y  t he partici pa nt’s cli nical state or c o nc o mita nt 
t hera pies a n d ma y a p pear, wit h s o me de gree of certai nt y, t o be relate d base d o n 
t he k n o w n t hera pe utic a n d p har mac ol o gic acti o ns of t he dr u g. G o o d cli nical 
j u d ge me nt s h o ul d be use d f or deter mi ni n g ca usal assess me nt.
7. 2. 1. 4. U ne x pecte d A d verse Re acti o ns
A n a d verse e ve nt is ‘ u ne x pecte d’ if its nat ure a n d se verit y are n ot c o nsiste nt wit h t he 
i nf or mati o n a b o ut t he st u d y dr u g pr o vi de d i n t he Refere nce Safety I nf or mati o n ( R SI) i n t he 
v o xel ot or I B.
7. 2. 2. A d verse E ve nt R e p orti n g 
7. 2. 2. 1. Ge ner al
F or st u d y partici pa nts tra nsiti o ni n g fr o m t he pri mar y  st u d y ( G B T 4 4 0-0 3 1), all A Es ( b ot h 
seri o us a n d n o nseri o us) will be rec or de d fr o m t he ti me b ot h i nf or me d c o nse nt is o btai ne d f or 
t his e xte nsi o n st u d y a n d E n d of Treat me nt ( E o T) visit has bee n c o m plete d i n t he pri mar y 
st u d y ( G B T 4 4 0-0 3 1) u ntil 2 8 da y s after last d ose of st u d y dr u g or E n d of S t u d y visit i n t his 
st u d y.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 5
Bef ore E o T visit is c o m plete d i n t he pri mar y st u d y ( G B T 4 4 0-0 3 1), st u d y  sites m ust c o nti n ue 
t o c ollect a n d re p ort t o Pfizer Safet y , S A E t hr o u g h a n d i ncl u di n g 2 8 cale n dar da ys after t he 
last d ose of t he i n vesti gati o nal pr o d uct (I P) or E o T visit , i n t he pri mar y st u d y, e ve n t h o u g h 
t he patie nt ma y ha ve si g ne d t he i nf or me d c o nse nt (I C) or si g ne d t he I C a n d ta ke n t he first 
d ose o n t h e r oll o ver st u d y G B T 4 4 0- 0 3 4/C 5 3 4 1 0 2 2 . St u d y rec or di n g of a d verse e ve nts i n t he 
case re p ort f or m ( C R F) m ust c o nti n ue i n t he pri mar y  st u d y u ntil E o T visit is ac hie ve d.  
A d verse e ve nts re p orte d as o n g oi n g at t he c o m pleti o n of G B T 4 4 0 -0 3 1, will be rec or de d i n 
t he Me dical Hist or y C R F i n t his st u d y. 
After E n d of Treat me nt visit i n t he st u d y G B T 4 4 0- 0 3 1, re p orti n g of all A Es a n d S A Es i n t he 
st u d y G B T 4 4 0- 0 3 4/C 5 3 4 1 0 2 2 , m ust be pr o m ptl y d oc u me nte d o n t he A E C R F via t he E D C 
s yste m. Re q uire me nts f or i m me diate safety rep orti n g will f oll o w sta n dar d pr ocess as 
s pecifie d i n secti o n 7. 2. 3 .
T he i n vesti gat or is res p o nsi ble f or e val uati n g all A Es, o btai ni n g s u p p orti n g d oc u me nts, a n d 
e ns uri n g d oc u me ntati o n of t he e ve nt is c o m plete. Details of eac h re p orte d A E m ust i ncl u de at 
mi ni m u m se verit y , relati o ns hi p t o st u d y dr u g, d urati o n a n d o utc o me. All ( b ot h seri o us a n d 
n o nseri o us) A Es m ust be f oll o we d u ntil t he y  are res ol ve d or sta bilize d, or u ntil reas o na ble 
atte m pts t o deter mi ne res ol uti o n of t he e ve nt are e x ha uste d.
W he n a cli nicall y  i m p orta nt A E re mai ns o n g oi n g at t he e n d of t he acti ve c ollecti o n peri o d, 
f oll o w-u p b y  t he i n vesti gat or c o nti n ues u ntil t he A E or S A E or its se q uelae res ol ve or 
sta bilize at a le vel acce pta ble t o t he i n vesti gat or a n d Pfizer c o nc urs wit h t hat assess me nt. 
F or partici pa nts w h o are scree n fail ures, t he acti ve c ollecti o n peri o d e n ds w he n scree n fail ure 
stat us is deter mi ne d. 
If t he partici pa nt wit h dra ws fr o m t he st u d y a n d als o wit h dra ws c o nse nt f or t he c ollecti o n of 
f ut ure i nf or mati o n, t he acti ve c ollecti o n peri o d e n ds w he n c o nse nt is wit h dra w n. 
If a partici pa nt per ma ne ntl y disc o nti n ues or te m p orarily disc o nti n ues st u d y i nter ve nti o n 
beca use of a n A E or S A E, t he A E or S A E m ust be rec or de d o n t he C R F a n d t he S A E 
re p orte d usi n g P S S A. T he S p o ns or/ Me dical M o nit or(s) m ust be n otifie d of t he st u d y 
partic i pa nt disc o nti n uati o n. 
I n vesti gat ors are n ot o bli gate d t o acti vely see k i nf or mati o n o n A Es or S A Es after t he 
partici pa nt has c o ncl u de d st u d y  partici pati o n. H o we ver, if t he i n vesti gat or lear ns of a n y  S A E, 
i ncl u di n g a deat h, at a ny ti me after a partici pa nt has c o ncl u de d st u d y  partici pati o n, a n d t he y 
c o nsi der t he e ve nt t o be reas o na bl y relate d t o t he st u d y  i nter ve nti o n, t he i n vesti gat or m ust 
pr o m ptl y  re p ort t he S A E t o Pfizer usi n g P S S A.
7. 2. 2. 2. Di a g n osis Vers us Si g ns a n d S y m pt o ms
If k n o w n, a dia g n osis s h o ul d be rec orde d o n t he C R F rat her t ha n i n di vi d ual si g ns a n d 
s ym pt o ms ( e g, rec or d o nl y li ver fail ure or he patitis rat her t ha n ja u n dice, asteri xis, a n d 
ele vate d tra nsa mi nases). H o we ver, if a c o nstellati o n of si g ns a n d/ or s y m pt o ms ca n n ot be 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 6
me dicall y  c haracterize d as a si n gle dia g n osis or sy n dr o me at t he ti me of re p orti n g, eac h 
i n di vi d ual e ve nt s h o ul d be rec or de d se paratel y o n t he C R F. If a dia g n osis is s u bse q ue ntl y 
esta blis he d, it s h o ul d be re p orte d as f oll o w -u p i nf or mati o n.
7. 2. 2. 3. A b n or m al L a b or at or y V al ues
O nl y  cli nicall y si gnifica nt la b orat or y  a b n or malities as assesse d by t he I n vesti gat or will be 
rec or de d o n t he A E C R F (e g, a b n or malities t hat ha ve cli nical se q uelae, re q uire st u d y dr u g 
d ose m o dificati o n, etc.). If t he cli nicall y si g nifica nt la b orat or y a b n or malit y is a si g n of a 
disease or s y n dr o me ( e g, A L K a n d bilir u bi n 5 x U L N ass ociate d wit h c h olec y stitis), o nl y t he 
dia g n osis ( e g, c h olec ystitis) s h o ul d be rec or de d as a n A E o n t he C R F. 
If t he cli nically si g nifica nt la b orat or y a b n or malit y is n ot a si g n of a disease or s y n dr o me, t he 
a b n or malit y itself, c haracterize d b y precise cli nical ter m, as p ossi ble, s h o ul d be rec or de d o n 
t he C R F (e g, ele vate d p otassi u m of 7. 0 m E q/ L  s h o ul d be rec or de d as ‘ h yper kale mia’).
O bser vati o ns of t he sa me cli nicall y  si g nifica nt la b orat or y a b n or malit y fr o m visit t o visit 
s h o ul d n ot be re peate dl y rec or de d o n t he A E C R F, u nless t heir se verit y, seri o us ness, or 
eti ol o g y c ha n ges. 
N ote : P ote ntial dr u g-i n d uce d li ver i nj ur y ( DI LI; H y’s la w) cases are t o be re p orte d as S A Es 
(Secti o n 7. 2. 3 ). F or s u g geste d acti o ns a n d f oll o w -u p assess me nts i n t he e ve nt of p ote ntial 
DI LI, refer t o A p pe n di x 2 . ( T his n ote is i ncl u de d t o s u p p ort St u d y tra nsiti o n t o Pfizer 
P har mac o vi gila nce pr ocesses a n d s y ste ms.)
7. 2. 2. 4. Pree xisti n g Me dic al C o n diti o ns
A pree xisti n g me dical c o n diti o n is o ne t hat is prese nt a t t he start of t he st u d y. S uc h 
c o n diti o ns s h o ul d be rec or de d o n t he Me dical Hist or y a n d Baseli ne C o n diti o ns C R F.
If a pree xisti n g me dical c o n diti o n i ncreases i n fre q ue nc y or se verity, or if t he c haracter of t he 
c o n diti o n w orse ns d uri n g t he st u d y , t he c o n diti o n s h o ul d be rec or de d as a n A E or S A E. 
W he n rec or di n g s uc h e ve nts o n t he A E C R F, it is i m p orta nt t o c o n ve y  t he c o nce pt t hat t he 
pree xisti n g c o n diti o n has c ha n ge d b y i ncl u di n g a p plica ble descri pt ors ( e g, “m ore fre q ue nt
hea dac hes”).
7. 2. 2. 5. W orse ni n g of Sic kle Cel l Dise ase
C o m plicati o ns a n d s ym pt o ms of S C D s h o ul d be rec or de d as a n A E or S A E if j u d ge d b y t he 
I n vesti gat or t o ha ve w orse ne d i n se verit y a n d/ or fre q ue nc y or c ha n ge d i n nat ure d uri n g t he 
st u d y. 
7. 2. 3. Seri o us A d verse E ve nts, Seri o us A d verse Dr u g Re acti o ns, a n d R e q uire me nts f or 
I m me di ate Re p orti n g
All S A Es, re gar dless of ca usal attri b uti o n, occ urri n g o n t his st u d y  will be rec orte d o n t he A E 
e C R F a n d re p orte d t o Pfizer Safet y via P S S A wit hi n 2 4 h o urs of t he I n vesti gat or, desi g nee, 
or site pers o n nel’s k n o wle d ge of t he e ve nt. I n t he e ve nt t hat t he E D C s ys te m is n ot a vaila ble, 
pa per S A E re p ort f or ms will be use d t o re p ort t he S A E a n d fa xe d or e maile d t o Pfizer Safet y . 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 7
T he i nf or mati o n re p orte d o n t he pa per S A E re p ort f or m s h o ul d be e ntere d i nt o P S S A o nce 
a vaila ble.
T he S p o ns or ma y  re q uest a d diti o nal i nf or mati o n pertai ni n g t o t he S A E fr o m t he 
i n vesti gati o nal site. F oll o w- u p re p orts m ust be s u b mitte d wit hi n 2 4 h o urs of a ware ness as 
a d diti o nal i nf or mati o n bec o mes a vaila ble.
All S A Es re gar dless of ca usal attri b uti o n m ust be f oll o we d t o res ol uti o n, sta bilizati o n or u ntil 
reas o na ble atte m pts t o deter mi ne res ol uti o n of t he S A E are perf or me d.
7. 2. 3. 1. Re p orti n g S us pecte d U ne x pecte d Seri o us A d verse Re acti o ns ( S U S A Rs) a n d 
Ur ge nt S afet y Iss ues
T he S p o ns or is res p o nsi ble f or re p orti n g S us pect e d U ne x pecte d Seri o us A d verse Reacti o ns 
( S U S A Rs) t o re g ulat or y a ge ncies, c o m pete nt a ut h orities, IR Bs/ E Cs, a n d I n vesti gat ors, as per 
l ocal la ws a n d re g ulati o ns. Fatal a n d life-t hreate ni n g S U S A Rs will be s u b mitte d n o later t ha n 
7- cale n dar da ys of first k n o wle d ge of t he e ve nt a n d f oll o w -u p i nf or mati o n s u b mitte d wit hi n 
a n a d diti o nal 8 cale n dar da ys, or as ot her wise re q uire d per l ocal la ws a n d re g ulati o ns. All 
ot her S U S A Rs will be s u b mitte d wit hi n 1 5 -cale n dar da ys of first k n o wle d ge of t he e ve nt. 
T he I n vesti gat o r is res p o nsi ble f or n otif yi n g t he l ocal I R B or l ocal E Cs of all S A Es t hat occ ur 
at his or her site as re q uire d b y  l ocal re g ulati o ns or IR B/ E C p olicies, if t his res p o nsi bilit y  
resi des wit h t he site.
I n vesti gat ors are re q uire d t o re p ort a ny ur ge nt safet y matters t o t he S p o ns or wit hi n 2 4 h o urs. 
T he S p o ns or will i nf or m re g ulat or y  a ut h orities, I R Bs/ E Cs, a n d I n vesti gat ors of a n y e ve nts 
(e g, c ha n ge t o t he safet y pr ofile of v o xel ot or, maj or safet y fi n di n gs t hat ma y place st u d y 
partici pa nts at ris k) t hat ma y  occ ur d uri n g t he cli nical trial t hat d o n ot fall wit hi n t he 
defi niti o n of a S U S A R b ut ma y  a d versely affect t he safet y of st u d y partici pa nts, as re q uire d, 
i n acc or da nce wit h a p plica ble l ocal la ws a n d re g ulati o ns. T he re p orti n g peri o d f or ur ge nt 
safety iss ues is t he peri o d fr o m si g ni n g t he i nf or me d c o nse nt u ntil 2 8 da ys after last d ose of 
st u d y dr u g or E O S visit o n G B T 4 4 0- 0 3 4/C 5 3 4 1 0 2 2 . 
7. 2. 4. Re p orti n g O ver d ose
If a partici pa nt ta kes m ore t ha n t he pr ot oc ol -defi ne d d ose i n a da y  a n d e x perie nces a dr u g-
relate d A E, t his will be re p orte d as a n o ver d ose a n d a pr ot oc ol de viati o n. H o we ver, if t he 
partici pa nt di d n ot e x perie nce a n y A Es, t his will o nl y be re p orte d as a pr ot oc ol de viati o n. 
T he I n vesti gat or will disc uss t he ris ks a n d c o ncer ns of i n vesti gati o nal a ge nt e x p os ure wit h 
t he partici pa nt. Pare nts, g uar dia ns or partici pa nts are t o be i nstr ucte d t o c o ntact t heir st u d y 
site i m me diatel y if a n o ver d ose of st u dy dr u g is s us pecte d. A n o ver d ose wit h A Es m ust be 
f oll o we d u ntil t he a d verse effects are res ol ve d or sta bilize d, or u ntil reas o na ble atte m pts t o 
deter mi ne res ol uti o n of t he e ve nt are e x ha uste d. 
I n t he e ve nt of a n o ver d ose, t he I n vesti gat or or treati n g p hys icia n s h o ul d:

C o ntact t he st u d y  Me dical M o nit or wit hi n 2 4 h o urs.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 8

Cl osel y  m o nit or t he partici pa nt f or a ny A Es/ S A Es a n d la b orat or y a b n or malities as 
me dicall y  a p pr o priate a n d f oll o w u p u ntil res ol uti o n, sta bilizati o n, t he e ve nt is 
ot her wise e x plai ne d, or t he partici pa nt is l ost t o f oll o w - u p. 

D oc u me nt t he q ua ntit y of t he e xcess d ose as well as t he d urati o n of t he o ver d ose 
i n t he e C R F.

Re p ort t o S p o ns or Safet y o nl y  w he n ass ociate d wit h a n S A E.
7. 3. E n vir o n me nt al E x p os ure, E x p os ure D uri n g Pre g n a nc y or Bre astfee di n g, a n d 
Occ u p ati o n al E x p os ure
E n vir o n me ntal e x p os ure occ urs w he n a pers o n n ot e nr olle d i n t he st u d y as a partici pa nt 
receives u n pla n ne d direct c o ntact wit h or e x p os ure t o v o xel ot or. S uc h e x p os ure ma y  or ma y 
n ot lea d t o t he occ urre nce of a n A E or S A E. Pers o ns at ris k f or e n vir o n me ntal e x p os ure 
i ncl u de healt hcare pr o vi ders, fa mily me m bers, a n d ot hers w h o ma y  be e x p ose d. A n 
e n vir o n me ntal e x p os ure ma y i ncl u de e x p os ure d uri n g pre g na nc y ( E D P), e x p os ure d uri n g 
breastfee di n g ( E D B), a n d occ u pati o nal e x p os ure.
A n y  s uc h e x p os ures t o v o xel ot or u n der st u d y are re p orta ble t o Pfizer Safet y  wit hi n 2 4 h o urs 
of I n vesti gat or a ware ness.
7. 3. 1. E x p os ure D uri n g Pre g n a nc y
A n E D P occ urs if:

A fe male partici pa nt is f o u n d t o be pre g na nt w hile recei vi n g or after disc o nti n ui n g 
v o xel ot or.

A male partici pa nt w h o is recei vi n g or has disc o nti n ue d v o xel ot or i nse mi nates a 
fe male part ner.

A fe male n o n partici pa nt is f o u n d t o be pre g na nt w hile bei n g e x p ose d or ha vi n g 
bee n e x p ose d t o v o xel ot or beca use of e n vir o n me ntal e x p os ure. Bel o w are
e xa m ples of e n vir o n me ntal E D P:

A fe male fa mil y  me m ber of healt hcare pr o vi der re p orts t hat s he is pre g na nt 
after ha vi n g bee n e x p ose d t o v o xel ot or b y  all p ossi ble r o utes of e x p os ure, e g, 
i n gesti o n, i n halati o n, or s ki n c o ntact.

A male fa mil y me m ber or healt hcare pr o vi der w h o has bee n e x p ose d t o 
v o xel ot or b y  all p ossi ble r o utes of e x p os ure, e g, i n gesti o n, i n halati o n, or s ki n 
c o ntact, t he n i nse m i nates his fe male part ner pri or t o or ar o u n d t he ti me of 
c o nce pti o n.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 3 9
T he I n vesti gat or m ust re p ort E D P t o Pfizer Safet y wit hi n 2 4 h o urs of t he I n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nitial i nf or mati o n s u b mitte d 
s h o ul d i ncl u de t he a ntici pate d date of deli ver y (see bel o w of i nf or mati o n relate d t o 
ter mi nati o n of pre g na nc y). 

If E D P occ urs i n a partici pa nt/ partici pa nt’s part ner, t he In vesti gat or m ust re p ort 
t his i nf or mati o n t o Pfizer Safet y via P S S A re gar dless of w het her a n S A E has 
occ urre d. Details of t he pre g na nc y  will be c ollecte d after t he start of v o xel ot or 
a n d u ntil at least 1 4 0 da ys after t he last d ose.

If E D P occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, t he I n vesti gat or m ust 
re p ort i nf or mati o n t o Pfizer Safet y vi a P S S A . Si nce t he e x p os ure i nf or mati o n 
d oes n ot pertai n t o t he partici pa nt e nr olle d i n t he st u d y , t he i nf or mati o n is n ot 
rec or de d o n a C R F; h o we ver, a c o py of t he c o m plete d re p ort is mai ntai ne d i n t he 
I n vesti gat or site file.
F oll o w -u p is c o n d ucte d t o o bta i n ge neral i nf or mati o n o n t he pre g na nc y a n d its o utc o me f or 
all E D P re p orts wit h a n u n k n o w n o utc o me. T he I n vesti gat or will f oll o w t he pre g na nc y u ntil 
c o m pleti o n ( or u ntil pre g na nc y  ter mi nati o n) a n d n otif y Pfizer Safety of t he o utc o me as a 
f oll o w- u p t o t he i nitial re p ort. I n t he case of a li ve birt h, t he str uct ural i nte grit y of t he ne o nate 
ca n be assesse d at t he ti me of birt h. T he c hil d b or n t o a fe male partici pa nt or part ner of a 
male partici pa nt e x p ose d t o st u d y  dr u g will be f oll o we d f or 3 m o nt hs after del i ver y. I n t he 
e ve nt of a ter mi nati o n, t he reas o n(s) f or ter mi nati o n s h o ul d be s pecifie d a n d, if cli nicall y  
p ossi ble, t he str uct ural i nte grit y of t he ter mi nate d fet us s h o ul d be assesse d b y gr oss vis ual 
i ns pecti o n ( u nless pre-pr oce d ure test fi n di n gs are c o nc l usi ve f or a c o n ge nital a n o maly a n d 
t he fi n di n gs are re p orte d).
A b n or mal pre g na nc y  o utc o mes are c o nsi dere d S A Es. If t he o utc o me of t he pre g na nc y meets 
t he criteria f or a n S A E (ie, ect o pic pre g na nc y, s p o nta ne o us a b orti o n, i ntra uteri ne fetal 
de mise, ne o natal deat h, or c o n ge nital a n o mal y i n a li ve b or n ba b y, a ter mi nate d fet us, a n 
i ntra uteri ne fetal de mise, or a ne o natal deat h), t he I n vesti gat or s h o ul d f oll o w t he pr oce d ures 
f or re p orti n g S A Es. A d diti o nal i nf or mati o n a b o ut pre g na nc y o utc o mes t hat are re p orte d to 
Pfizer Safet y  as S A Es f oll o ws:

S p o nta ne o us a b orti o n i ncl u di n g miscarria ge a n d misse d a b orti o n s h o ul d be 
re p orte d as a n S A E;

Ne o natal deat hs t hat occ ur wit hi n 1 m o nt h of birt h s h o ul d be re p orte d, wit h o ut 
re gar d t o ca usality, as S A Es. I n a d diti o n, i nfa nt d eat hs after 1 m o nt h s h o ul d be 
re p orte d as S A Es w he n t he I n vesti gat or assesses t he i nfa nt deat h as relate d or 
p ossi bl y  relate d t o e x p os ure t o v o xel ot or.
A d diti o nal i nf or mati o n re gar di n g t he E D P ma y  be re q ueste d b y t he S p o ns or. F urt her f oll o w-
u p of birt h o ut c o mes will be ha n dle d o n a case -b y -case basis (e g, f oll o w- u p o n preter m 
i nfa nts t o i de ntif y de vel o p me ntal dela ys). I n t he case of pater nal e x p os ure, t he In vesti gat or 
will pr o vi de t he partici pa nt wit h t he Pare ntal Part ner: I nf or mati o n S heet a n d I nf or me d 
C o n se nt F or m t o deli ver t o his part ner. T he I n vesti gat or m ust d oc u me nt i n t he s o urce 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 0
d oc u me nts t hat t he partici pa nt was gi ve n t he Pre g na nt Part ner Release of I nf or mati o n F or m 
t o pr o vi de t o his part ner. 
7. 3. 2. E x p os ure D uri n g Bre astfee di n g
A n E D B occ urs if:
•
A fe ma le partici pa nt is f o u n d t o be breastfee di n g w hile recei vi n g or after disc o nti n ui n g 
v o xel ot or.
•
A fe male n o n partici pa nt is f o u n d t o be breastfee di n g w hile bei n g e x p ose d or ha vi n g bee n 
e x p ose d t o v o xel ot or (ie, e n vir o n me ntal e x p os ure). A n e xa m ple of e n vir o n me ntal E D B is a 
fe male fa mil y me m ber or healt hcare pr o vi der w h o re p orts t hat s he is breastfee di n g after 
ha vi n g bee n e x p ose d t o v o xel ot or b y  all p ossi ble r o utes of e x p os ure, e g, i n gesti o n, 
i n halati o n, or s ki n c o ntact.
T he I n vesti gat or m ust re p ort E D B t o Pfizer Safet y wit hi n 2 4 h o urs of t he I n vesti gat or’s 
a ware ness, irres pecti ve of w het her a n S A E has occ urre d. T he i nf or mati o n m ust be re p orte d 
usi n g t he P S S A. W he n E D B occ urs i n t he setti n g of e n vir o n me ntal e x p os ure, t he e x p os ure 
i nf or mati o n d oes n ot pertai n t o t he partici pa nt e nr olle d i n t he st u d y, s o t he i nf or mati o n is n ot 
rec or de d o n a C R F. H o we ver, a c o py of t he c o m plete d re p ort is mai ntai ne d i n t he 
I n vesti gat or site file.
A n E D B re p ort is n ot create d w he n a Pfizer dr u g s pecificall y a p pr o ve d f or use i n 
breastfee di n g w o me n (e g, vita mi ns) is a d mi nistere d i n acc or da nce wit h a ut h orize d use. 
H o we ver, if t he i nfa nt e x perie nces a n S A E ass ociate d wit h s uc h a dr u g, t he S A E is re p orte d 
t o get her wit h t he E D B.
7. 3. 3. Occ u p ati o n al E x p os ure
T he I n vesti gat or m ust re p ort a n y i nsta nce of occ u pati o nal e x p os ure t o Pfizer Safet y wit hi n 2 4 
h o urs of t he I n vesti gat or’s a ware ness via P S S A re gar dless of w het her t here is a n ass ociate d 
S A E. Si nce t he i nf or mati o n a b o ut t he occ u pati o nal e x p os ure d oes n ot pertai n t o a partici pa nt 
e nr olle d i n t he st u d y, t he i nf or mati o n is n ot rec or de d o n a C R F; h o we ver, a c o p y  of t he 
c o m plete d re p ort is mai ntai ne d i n t he I n vesti gat or site file.
7. 4. L ac k Of Effic ac y 
T he i n vesti gat or m ust re p ort si g ns, s y m pt o ms, a n d/ or cli nical se q uelae res ulti n g fr o m lac k of 
efficac y. Lac k of efficac y or fail ure of e x pecte d p har mac ol o gical acti o n is re p orta ble t o 
Pfizer Safet y  o nl y if ass ociate d wit h a n S A E.
7. 5. Me dic ati o n Err ors
Me dicati o n err ors m a y  res ult fr o m t he a d mi nistrati o n or c o ns u m pti o n of v o xel ot or b y t he 
wr o n g partici pa nt, or at t he wr o n g ti me, or at t he wr o n g d osa ge stre n gt h.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 1
Me dicati o n err ors are rec or de d a n d re p orte d as f oll o ws:
T a ble 8.
Re p orti n g o f Me dic ati o n Err ors
Rec or de d o n t he Me dic ati o n 
P a ge of t he C R F
Rec or de d o n t he A d verse 
E ve nt P a ge of t he C R F
Re p orte d vi a P S S A t o Pfizer 
S afet y Wit hi n 2 4 H o urs of 
A w are ness
All (re gar dless of w het her 
ass ociate d wit h a n A E)
A n y A E or S A E ass ociate d 
wit h t he me dicati o n err or
O nl y if ass ociate d wit h a n S A E
A b bre viati o ns: A E, a d verse e ve nt; C R F, case re p ort f or m; S A E, seri o us a d verse e ve nt; P S S A: 
Pfizer's Seri o us A E S u b missi o n Assista nt
Me dicati o n err ors i ncl u de:

Me dicati o n err ors i n v ol vi n g partici pa nt e x p os ure t o t he st u d y dr u g

P ote ntial me dicati o n err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol t hat 
d o or d o n ot i n v ol ve t he st u d y  partici pa nt;

T he a d mi nistrati o n of a n i nc orrect d osa ge;

T he a d mi nistrati o n of e x pire d st u d y  dr u g;

T he a d mi nistrat i o n of a n i nc orrect st u d y dr u g;

T he a d mi nistrati o n of st u d y  dr u g t hat has u n der g o ne te m perat ure e xc ursi o n fr o m 
t he s pecifie d st ora ge ra n ge u nless it is deter mi ne d b y t he S p o ns or t hat t he st u d y 
dr u g u n der q uesti o n is acce pta ble t o use.
W het her or n ot t he me dicati o n err or is acc o m pa nie d b y  a n A E, as deter mi ne d b y t he 
I n vesti gat or, s uc h me dicati o n err ors occ urri n g t o a st u d y partici pa nt are rec or de d o n t he 
me dicati o n err or pa ge of t he C R F, w hic h is a s pecific versi o n of t he A E pa ge a n d, if 
a p plica ble, a n y ass ociate d seri o us a n d n o nseri o us A E(s) are rec or de d o n t he A E pa ge of t he 
C R F.
I n t he e ve nt of a me dicati o n d osi n g err or, t he S p o ns or s h o ul d be n otifie d wit hi n 2 4 h o urs.
Me dicati o n err ors s h o ul d be re p orte d t o Pfizer Safet y wit hi n 2 4 h o urs usi n g P S S A o nl y  w hen 
ass ociate d wit h a n S A E.
7. 6. D at a a n d S afet y M o nit ori n g B o ar d
N ot a p plica ble t o t his o pe n la bel trial.
8. BI O S T A TI S TI C S
8. 1. St atistic al Met h o ds
Statistical pr o gra m mi n g a n d a nal ys es will be perf or me d usi n g esta blis he d statistical met h o ds. 
Details of all pla n ne d a nal y ses will be s pecifie d i n a se parate statistical a nal ysis pla n ( S A P). 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 2
T he st u d y  data will be re p orte d usi n g s u m mar y ta bles, fi g ures, a n d data listi n gs. C o ntin u o us 
varia bles will be s u m marize d usi n g mea n, sta n dar d de viati o n ( S D), me dia n, mi ni m u m, a n d 
ma xi m u m. Cate g orical varia bles will be s u m marize d b y  prese nti n g t he n u m ber (fre q ue nc y) 
a n d perce nta ge i n eac h cate g or y .
8. 1. 1. St u d y E n d p oi nts
8. 1. 1. 1. S afet y 
Safet y  data a nal ys is will be perf or me d o n all partici pa nts e nr olle d i n t he st u d y.
A treat me nt - e mer ge nt a d verse e ve nt ( T E A E) is defi ne d as a n A E t hat e mer ges o n or after 
i nitiati o n of st u d y dr u g ( ha vi n g bee n a bse nt pretreat me nt), or a n A E t hat e xiste d pretreat me nt 
a n d w orse ne d o n treat me nt (relati ve t o t he pretreat me nt state). T he i nci de nce of T E A Es will 
be ta b ulate d b y s ys te m or ga n class ( S O C), preferre d ter m, se verity a n d relati o ns hi p t o st u d y  
dr u g. A Es c o nsi dere d t o be relate d b y t he I n vesti gat or will be s u m marize d. A Es will be 
re p orte d by se verit y a n d relate d ness t o st u d y treat me nt a n d classifie d via t he Me dical 
Dicti o nar y  f or Re g ulat or y Acti vities ( Me d D R A).
C ha n ges i n cli nical la b orat or y  data ( he mat ol o g y, ser u m c he mistr y, 
 
) will be s u m marize d.
F or t he la b orat or y  safety data , o ut of ra n ge val ues will be fla g ge d i n t he data listi n gs a n d a 
list of cli nicall y si g nifica ntl y a b n or mal val ues will be prese nte d.
8. 1. 1. 2. Fre q ue nc y of S C D -Rel ate d C o m plic ati o ns
O ver t he c o urse of t he treat me nt per i o d, t he fre q ue nc y of S C D c o m plicati o ns f or eac h 
partici pa nt will be rec or de d. S C D c o m plicati o ns ma y i ncl u de t he f oll o wi n g: V O C, ac ute 
c hest s yn dr o me, he patic se q uestrati o n, le g ulcers, pria pis m, p ul m o nar y  h yperte nsi o n, 
reti n o pat h y, scleral icter us, s ple nic se q uestrati o n, a n d str o ke. T he i nci de nce a n d rate of eac h 
c o m plicati o n a n d t he t otalit y of all S C D-relate d c o m plicati o ns will be c o m p ute d a n d t he n 
c o m pare d t o t h ose o bser ve d i n t he G B T 4 4 0 -0 3 1 st u d y . 
8. 1. 1. 2. 1. T her a pies Ass oci ate d wit h V O C
D uri n g t he treat me nt per i o d, R B C tra nsf usi o n a n d o pi oi d usa ge will be rec or de d. T he 
i nci de nce a n d rate of t hese t hera pies will be calc ulate d a n d c o m pare d t o t h ose o bser ve d i n t he 
G B T 4 4 0 -0 3 1 st u d y .
8. 1. 1. 3. Res p o nse i n He m ol ytic A ne mi a
At eac h sc he d ule d la b orat or y  assess me nt, he mat ol o g y a nd ser u m c he mistr y will be meas ure d 
t o deter mi ne l o n git u di nal d ura bilit y of res p o nse wit h re gar ds t o he m olyt ic a ne mia. Of 
partic ular i nterest are he m o gl o bi n, bilir u bi n, a n d retic ul oc yte c o u nts. T here will be t w o 
baseli ne val ues use d t o descri be efficac y  a n d d ura bilit y : ( 1) Baseli ne deri ve d fr o m t he pre-
d ose he mat ol o g y  meas ure me nts o btai ne d d uri n g t he G B T 4 4 0-0 3 1 st u d y  a n d ( 2) He mat ol o g y 
meas ure me nts o btai ne d via pre -d ose o n Da y  1 i n t his st u d y. C ha n ge fr o m baseli ne, a n d 
perce nt c ha n ge fr o m baseli ne f or t he t w o af ore me nti o ne d baseli ne val ues will be c o m p ute d t o 
deter mi ne tre n ds o ver t he d urati o n of treat me nt. 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)
C CI

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 3
8. 2. S a m ple Size
T he sa m ple size f or t his st u d y  will n ot e xcee d t he t otal e nr oll me nt of t he G B T 4 4 0-0 3 1 st u d y .
8. 3. Le vel of Si g nific a nce
All statistical a nal y ses co n d ucte d will be descri pti ve a n d n o f or mal statistical tests will be 
perf or me d. 
8. 4. St atistic al Criteri a f or Ter mi n ati o n of t he Tri al
N o f or mal statistical criteria will be use d f or ter mi nati o n of t he trial. 
8. 5.
Missi n g, U n use d, or S p uri o us D at a
Data will be s u m marize d as o bser ve d wit h n o i m p utati o n f or missi n g val ues, e xce pti n g 
partiall y  missi n g dates. F ull details of h o w missi n g date data will be ha n dle d will be 
descri be d i n t he S A P.
8. 6. De vi ati o n fr o m t he St atistic al A n al ysis Pl a n
De viati o ns fr o m t he S A P will be d escri be d i n eit her a n u p date d S A P or i n t he Cli nical St u d y  
Re p ort. 
8. 7. A n al ysis P o p ul ati o n
All partici pa nts w h o si g n t he I C F a n d recei ve v o xel ot or treat me nt i n t his st u d y  will be 
i ncl u de d i n t he a nalys es. Partici pa nts will be assi g ne d t o c o h orts base d u p o n t h e treat me nt 
recei ve d d uri n g t he G B T 4 4 0-0 3 1 st u d y , t hese c o h orts are as f oll o ws:
1.
Partici pa nts treate d wit h place b o d uri n g G B T 4 4 0 -0 3 1 w h o tra nsiti o n i nt o t he O L E
2.
Partici pa nts treate d wit h t he d ose n ot selecte d d uri n g G B T 4 4 0 -0 3 1 w h o tra nsiti o n 
i nt o t he O LE.
3.
P artici pa nts treate d wit h t he selecte d d ose d uri n g G B T 4 4 0 -0 3 1 w h o tra nsiti o n i nt o t he 
O L E.
9. DI R E C T A C C E S S T O S O U R C E D A T A/ D O C U M E N T S
9. 1. S o urce D at a
Ori gi nal d oc u me nts, data, rec or ds ( e g, cli nic rec or ds, la b orat or y n otes, me m ora n da, 
partici pa nt diaries or e val uati o n c hec klists, p har mac y  dis pe nsi n g rec or ds, rec or de d data fr o m 
a ut o mate d i nstr u me nts, c o pies or tra nscri pti o ns certifie d after verificati o n as bei n g acc urate 
a n d c o m plete, micr ofic hes, p h ot o gra p hic ne gati ves, micr ofil m or ma g netic me dia, X -r a ys, 
partici pa nt files, a n d rec or ds ke pt at t he p har mac y , at t he la b orat ories, a n d at me dic o-
tec h nical de part me nts i n v ol ve d i n t he cli nical trial), a n d all rele va nt secti o ns of t he 
partici pa nt’s me dical rec or ds a n d all ot her data c ollecti o n ma de s pecific t o t his trial c o nstit ute 
s o urce d oc u me nts.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 4
T he c o m plete d C R F is n ot a s o urce d oc u me nt. T he I n vesti gat or/i nstit uti o n will per mit trial 
relate d- m o nit ori n g, a u dits, I R B/ E C re vie w a n d re g ulat or y  i ns pecti o n b y pr o vi di n g direct 
access t o s o urce d oc u me nts.
9. 2. D at a C oll ecti o n
T he I n vesti gat or will be res p o nsi ble f or mai ntai ni n g acc urate a n d a de q uate case rec or ds 
(s o urce d oc u me nts) fr o m w hic h data will be tra nscri be d ( or if E D C s o urce data, tra nsferre d) 
t o C R Fs desi g ne d t o rec or d data perti ne nt t o t his st u d y . All rele va nt o bser vati o ns a n d data 
relate d t o t he st u dy will be s o rec or de d. T his will i ncl u de me dical a n d me dicati o n hist or y, 
p h y sical e xa mi nati o ns, a c hec klist of i ncl usi o n a n d e xcl usi o n criteria, i n vesti gati o nal 
treat me nt a d mi nistrati o n, a rec or d of sa m ple c ollectio n, cli nical assess me nts, A Es, a n d fi nal 
e val uati o n(s). T he m o nit or will re vie w all C R Fs a n d c o m pare data t o t hat c o ntai ne d i n cli nic 
n otes a n d partici pa nts’ s o urce d oc u me nts/ me dical rec or ds.
Data f or eac h partici pa nt will be rec or de d o n t he C R F. A C R F m us t be c o m plete d f or e ver y 
partici pa nt e nr olle d i n t he st u d y . W he n data are c o m plete, t he I n vesti gat or or me dically 
q ualifie d s u b -I n vesti gat or liste d o n F or m F D A 1 5 7 2 will a p pl y his/ her si g nat ure o n t he C R F 
i n dicati n g he/s he has re vie we d a n d a p pr o ves of t he data c ollecte d o n C R F. 
9. 3. Esse nti al D oc u me nt ati o n Re q uire me nts
T he S p o ns or or S p o ns or’s re prese ntati ve will c ollect fr o m t he i n vesti gati o nal site t he re q uire d 
esse ntial re g ulat or y d oc u me nts per I C H g ui da nce pri or t o v o xel ot or s hi p me nt t o t he site.
1 0. Q U A LI T Y C O N T R O L A N D Q U A LI T Y A S S U R A N C E
1 0. 1. M o nit ori n g
Site pers o n nel will be pr o vi de d wit h trai ni n g o n h o w t o c ollect q ualit y  data f or t he st u d y, a n d 
a S p o ns or m o nit or will be c o ntacti n g t he site peri o dicall y  t o re vie w st u d y c o n d uct a n d data 
rec or de d at t he site. At t he S p o ns or’s discreti o n, o n -site m o nit ori n g visits ma y be c o n d ucte d 
pre -st u d y, d uri n g t he st u d y, a n d f oll o wi n g st u d y c o m pleti o n. T hese visits are t o pr o vi de t he 
S p o ns or wit h t he o p p ort u nit y  t o e val uate st u d y pr o gress; verif y t he acc urac y a n d 
c o m plete ness of s o urce data a n d C R Fs; a n d e ns ure t hat all pr ot oc ol a n d G C P re q uire me nts, 
a p plica ble U S F D A or c o u ntr y -s pecific re g ulati o ns, a n d I n vesti gat or o bli gati o ns are bei n g 
f ulfille d. T he S p o ns or ma y ter mi nate st u d y partici pati o n b y a cli nical st u d y site if st u d y-site 
pers o n nel d o n ot f oll o w t he pr ot oc ol or G C Ps. A d diti o nall y , i n di vi d ual partici pa nts ma y be 
e xcl u de d if a me dical rec or ds re vie w i n dicates pr ot oc ol vi olati o ns or if ot her fact ors a p pear t o 
je o par dize t he vali dit y of t he st u d y.
T he I n vesti gat or a grees 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 ble ms detecte d 
d uri n g t he c o urse of t hese m o nit ori n g visits are res ol ve d.
1 0. 2. L a b or at or y Accre dit ati o n
T he la b orat or y  facilit y use d f or a nalys is of cli nical la b orat or y sa m ples m ust pr o vi de e vi de nce 
of a de q uate li ce ns ure or accre ditati o n. C o pies of la b orat or y certificati o n, lice ns ure, a n d 
refere nce ra n ges (as a p pr o priate) will be s u p plie d t o t he S p o ns or pri or t o st u d y i nitiati o n. T he 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 5
S p o ns or or desi g nee s h o ul d be n otifie d of a n y c ha n ges i n refere nce ra n ge val ues or
certificati o n/lice nse re ne wal d uri n g t he c o urse of t he st u d y .
1 0. 3. S p o ns or’s Me dic all y Q u alifie d I n di vi d u al
T he c o ntact i nf or mati o n f or t he s p o ns or’s Me dicall y Q ualifie d I n di vi d ual ( M QI; ie, Me dical 
M o nit or) f or t he st u d y is d oc u me nte d i n t he st u d y c o ntact lis t l ocate d i n t he St u d y Bi n der. 
T o facilitate access t o t heir I n vesti gat or a n d t he S p o ns or’s M QI f or st u d y -relate d me dical 
q uesti o ns or pr o ble ms fr o m n o nst u d y  healt hcare pr ofessi o nals, partici pa nts are pr o vi de d wit h 
a n e mer ge nc y c o ntact car d ( E C C) at t he ti me of i nf or me d c o nse nt. T he E C C c o ntai ns, at a 
mi ni m u m (a) pr ot oc ol a n d st u d y  i nter ve nti o n i de ntifiers, ( b) partici pa nt’s st u d y i de ntificati o n 
n u m ber, a n d (c) site e mer ge nc y  p h o ne n u m ber acti ve 2 4 h o urs/ da y, 7 da ys per wee k, a n d ( d) 
Pfizer Call Ce nter n u m ber .
T he E C C is i nte n de d t o a u g me nt, n ot re place, t he esta blis he d c o m m u nicati o n pat h wa y s 
bet wee n t he partici pa nt a n d t heir I n vesti gat or a n d site staff, a n d bet wee n t he I n vesti gat or a n d 
S p o ns or st u d y  tea m. T he E C C is o nl y t o be use d b y healt hcare pr ofessi o nals n ot i n v ol ve d i n 
t he researc h st u dy, as a mea ns of reac hi n g t he I nvesti gat or or site staff relate d t o t he care of a 
partici pa nt. T he Pfizer Call Ce nter n u m ber is t o be use d w he n t he i n vesti gat or a n d site staff 
are u na vaila ble. T he Pfizer Call Ce nter n u m ber is n ot f or use b y t he partici pa nt directl y;  if a 
partici pa nt calls t hat n u m ber directl y , t he y will be directe d bac k t o t he i n vesti gat or site.
1 1. R E G U L A T O R Y, E T HI C A L, L E G A L, A N D O V E R SI G H T O B LI G A TI O N S
1 1. 1. Re g ul at or y a n d Et hic al C o nsi der ati o ns
T his 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 wit h t he f oll o wi n g:

C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes, i ncl u di n g t he 
Declarati o n of Helsi n ki a n d CI O M S I nter nati o nal Et hical G ui deli nes;

A p plica ble I C H G C P g ui deli nes;

A p plica b le la ws a n d re g ulati o ns, i ncl u di n g a p plica ble pri vac y la ws.
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C D, S R S D(s), a n d ot her rele va nt d oc u me nts (e g, 
a d vertise me nts) m ust be re vie we d a n d a p pr o ve d b y  t he s p o ns or, s u b mitte d t o a n IR B/ E C b y  
t he i n vesti gat or, a n d re vie we d a n d a p pr o ve d b y t he IR B/ E C bef ore t he st u d y  is i nitiate d.
A n y  a me n d me nts t o t he pr ot oc ol will re q uire I R B/ E C a p pr o val bef ore i m ple me ntati o n of 
c ha n ges ma de t o t he st u d y desi g n, e xce 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  partici pa nts.
Pr ot oc ols a n d a n y s u bsta ntial a me n d me nts t o t he pr ot oc ol will re q uire healt h a ut h orit y  
a p pr o val pri or t o i nitiati o n e xce 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 partici pa nts.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 6
T he i n vesti gat or will be res p o nsi ble f or t he f oll o wi n g:

Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y  t o t he I R B/ E C a n n uall y or 
m ore fre q ue ntl y  i n acc or da nce wit h t he re q uire me nts, p olicies, a n d pr oce d ures 
esta blis he d b y t he I R B/ E C;

N otif y i n g t he I R B/ E C of S A Es or ot her si g nifica nt safety fi n di n gs as re q uire d b y 
I RB/ E C pr oce d ures;

Pr o vi di n g o versi g ht of t he c o n d uct of t he st u d y at t he site a n d a d here nce t o 
re q uire me nts of 2 1 C F R, I C H G C P g ui deli nes, t he IR B/ E C, E ur o pea n re g ulati o n 
5 3 6/ 2 0 1 4 f or cli nical st u dies, E ur o pea n Me dical De vice Re g ulati o n 2 0 1 7/ 7 4 5 f or 
cli nical de vice researc h, a n d all ot her a p plica ble l ocal re g ulati o ns.
1 1. 2. Re p orti n g of S afet y Iss ues a n d Seri o us Bre ac hes of t he Pr ot oc ol or I C H G C P
I n t he e ve nt of a ny pr o hi biti o n or restricti o n i m p ose d (ie, cli nical h ol d) b y a n a p plica bl e 
re g ulat or y a ut h orit y i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n t hat mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of t he st u d y 
i nter ve nti o n, Pfizer s h o ul d be i nf or me d i m me diatel y. 
I n a d diti o n, t he i n vesti gat or will i nf or m Pfizer i m me diatel y of a n y ur ge nt safety meas ures 
ta ke n by t he i n vesti gat or t o pr otect t he st u d y partici pa nts a gai nst a n y i m me diate hazar d, a n d 
of a n y seri o us b reac hes of t his pr ot oc ol or of t he I C H G C P g ui deli nes t hat t he i n vesti gat or 
be c o mes a ware of.
1 1. 3. I nf or me d C o nse nt a n d Asse nt Pr ocess
1 1. 3. 1. I nf or me d C o nse nt
T he I n vesti gat or or t he I n vesti gat or’s re prese ntati ve will e x plai n t he nat ure of t he st u d y , 
i ncl u di n g t he ris ks a n d be nefits, t o t he partici pa nt ( or t heir le gally a ut h orize d re prese ntati v e) 
a n d a ns wer all q uesti o ns re gar di n g t he st u d y. T he partici pa nt ( or t heir le gall y  a ut h orize d 
re prese ntati ve) s h o ul d be gi ve n s ufficie nt ti me a n d o p p ort u nit y t o as k q uesti o ns a n d t o deci de 
w het her or n ot t o partici pate i n t he trial.
Partici pa nts m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y . Partici pa nts ( or t heir 
le gall y a ut h orize d re prese ntati ve [if all o we d b y l ocal re g ulati o n]) will be re q uire d t o si g n a 
state me nt of i nf or me d c o nse nt t hat meets t he re q uire me nts of 2 1 C F R 5 0, l ocal re g ulati o ns, 
IC H g ui deli nes, pri vac y  a n d data pr otecti o n re q uire me nts, w here a p plica ble, a n d t he I R B/ E C 
or st u d y  ce nter. 
T he I n vesti gat or m ust e ns ure t hat eac h partici pa nt ( or t heir le gall y a ut h orize d re prese ntati ve) 
is f ull y i nf or me d a b o ut t he nat ure a n d o bjecti ves of t he st u d y, t he s hari n g of data relate d t o 
t he st u d y, a n d p ossi ble ris ks ass ociate d wit h partici pati o n, i ncl u di n g t he ris ks ass ociate d wit h 
t he pr ocessi n g of t he partici pa nt’s pers o nal data.
T he partici pa nt ( or t heir le gall y  a ut h orize d re prese ntati ve) m ust be i nf or me d t hat t heir 
pers o nal st u d y- relate d data will be use d b y t he S p o ns or i n acc or da nce wit h l ocal data 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 7
pr otecti o n la w. T he le vel of discl os ure m ust als o be e x plai ne d t o t he partici pa nt ( or t heir 
le gall y a ut h orize d re prese ntati ve).
T he partici pa nt ( o r t heir le gall y a ut h orize d re prese ntati ve) m ust be i nf or me d t hat t heir 
me dical rec or ds ma y  be e xa mi ne d b y Cli nical Q ualit y Ass ura nce a u dit ors or ot her a ut h orize d 
pers o n nel a p p oi nte d b y t he S p o ns or, b y  a p pr o priate IR B/ E C me m bers, a n d b y  i ns pect ors 
fr o m re g ulat or y a ut h orities.
T he I n vesti gat or f urt her m ust e ns ure t hat eac h st u d y  partici pa nt ( or t heir le gally a ut h orize d 
re prese ntati ve) is f ully i nf or me d a b o ut t heir ri g ht t o access a n d c orrect t heir pers o nal data a n d 
t o wit h dra w c o nse nt f or t he pr ocessi n g of t heir pers o nal data.
T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d 
bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date o n w hic h t he writte n c o nse nt was 
o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n t he I C F.
Partici pa nt s ( or t heir le gall y a ut h orize d re prese ntati ve) m ust be rec o nse nte d t o t he m ost 
c urre nt versi o n of t he I R B/ E C -a p pr o ve d I C F(s) d uri n g t heir partici pati o n i n t he st u d y  as 
re q uire d per l ocal re g ulati o ns.
A c o p y of t he I CF(s ) m ust be pr o vi de d t o t he partici pa nt ( or t heir le gall y a ut h orize d 
re prese ntati ve).
1 1. 3. 2. I nf or me d Asse nt
T he i n vesti gat or or t heir re prese ntati ve will e x plai n t he nat ure of t he st u d y  t o t he 
partici pa nt a n d t heir pare nt(s)/le gal g uar dia n a n d a ns wer all q uesti o ns re gar di n g t he 
st u d y. T he partici pa nt a n d t heir pare nt(s)/le gal g uar dia n s h o ul d be gi ve n s ufficie nt ti me a n d 
o p p ort u nit y  t o as k q uesti o ns a n d t o deci de w het her or n ot t o partici pate i n t he trial.
W he n c o nse nt is o btai ne d fr o m a
partici pa nt’s pare nt( s)/le gal g uar dia n, t he partici pa nt’s 
asse nt (affir mati ve a gree me nt) m ust be s u bse q ue ntl y o btai ne d w he n t he partici pa nt has t he 
ca pacit y t o pr o vi de asse nt, as deter mi ne d b y t he I R B/ E C. If t he i n vesti gat or deter mi nes t hat a 
partici pa nt’s decisi o nal ca pacit y is s o li mite d t he y ca n n ot reas o na bly be c o ns ulte d, t he n, as 
per mitte d b y  t he I RB/ E C a n d c o nsiste nt wit h l ocal re g ulat or y  a n d le gal re q uire me nts, t he 
partici pa nt’s asse nt ma y  be wai ve d wit h s o urce d oc u me ntati o n of t he reas o n asse nt was n ot 
o btai ne d. If t he st u d y partici pa nt d oes n ot pr o vi de t heir o w n asse nt, t he s o urce d oc u me nts 
m ust rec or d w h y t he partici pa nt di d n ot pr o vi de asse nt (f or e xa m ple, t he c hil d is n ot of 
asse nti n g a ge per l ocal re g ulati o ns or p olicies), h o w t he i n vesti gat or deter mi ne d t hat t he 
pe rs o n si g ni n g t he c o nse nt was t he partici pa nt’s pare nt(s)/le gal g uar dia n, t he c o nse nt si g ner’s 
relati o ns hi p t o t he st u d y partici pa nt, a n d t hat t he partici pa nt’s asse nt was o btai ne d or 
wai ve d. If asse nt is o btai ne d ver bally, it m ust be d oc u me nte d i n t he s o ur ce d oc u me nts.
If st u d y partici pa nts are mi n ors w h o reac h t he a ge of maj ority or if a c hil d reac hes t he a ge of 
asse nt ( per l ocal I R B/ E C re q uire me nts) d uri n g t he st u d y , as rec o g nize d u n der l ocal la w, t he 
c hil d or a d olesce nt m ust t he n pr o vi de t he a p pr o priate asse nt or c o nse nt t o d oc u me nt t heir 
willi n g ness t o c o nti n ue i n t he st u d y . F or a n a d olesce nt w h o reac hes t he a ge of c o nse nt, 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 8
pare ntal c o nse nt w o ul d n o l o n ger be vali d. If t he e nr oll me nt of e ma nci pate d mi n ors is 
per mitte d b y t he I RB/ E C a n d l ocal la w, t he pa rtici pa nt m ust pr o vi de d oc u me ntati o n of le gal 
stat us t o gi ve c o nse nt wit h o ut t he per missi o n of a le gall y a ut h orize d re prese ntati ve.
Partici pa nts a n d t heir pare nt(s)/le gal g uar dia n m ust be i nf or me d t hat t heir partici pati o n is 
v ol u ntar y . T he partici pa nt’s p are nt(s)/le gal g uar dia n will be re q uire d t o si g n a state me nt of 
i nf or me d c o nse nt t hat meets t he re q uire me nts of 2 1 C F R 5 0, l ocal re g ulati o ns, I C H 
g ui deli nes, HI P A A re q uire me nts, w here a p plica ble, a n d t he I R B/ E C or st u d y  ce nter.
T he i n vesti gat or m ust e ns ur e t hat eac h st u d y partici pa nt’s pare nt(s)/le gal g uar dia n a n d t he 
st u d y partici pa nt as a p plica ble are f ull y i nf or me d a b o ut t he nat ure a n d o bjecti ves of t he 
st u d y, t he s hari n g of data relate d t o t he st u d y, a n d p ossi ble ris ks ass ociate d wit h 
partici pati o n, i n cl u di n g t he ris ks ass ociate d wit h t he pr ocessi n g of t he partici pa nt’s pers o nal 
data.
T he partici pa nt’s pare nt(s)/le gal g uar dia n m ust be i nf or me d t hat t he partici pa nt’s pers o nal 
st u d y-relate d data will be use d b y t he s p o ns or i n acc or da nce wit h l ocal data pr otecti o n 
la w. T he le vel of discl os ure m ust als o be e x plai ne d t o t he partici pa nt’s pare nt(s)/le gal 
g uar dia n.
T he partici pa nt’s pare nt(s)/le gal g uar dia n m ust be i nf or me d t hat t he partici pa nt’s me dical 
rec or ds ma y be e xa mi ne d b y Cli nical Q uality Ass ura nce a u dit ors or ot her a ut h orize d 
pers o n nel a p p oi nte d b y t he s p o ns or, b y a p pr o priate I R B/ E C me m bers, a n d b y  i ns pect ors 
fr o m re g ulat or y a ut h orities.
T he i n vesti gat or f urt her m ust e ns ure t hat eac h st u d y  partici pa nt’s pare nt(s)/le gal g uar dia n is 
f ull y i nf or me d a bo ut t heir ri g ht t o access a n d c orrect t heir c hil d’s pers o nal data a n d t o 
wit h dra w c o nse nt f or t he pr ocessi n g of t heir c hil d’s pers o nal data, kee pi n g i n mi n d t he 
pri vac y  ri g hts t hat ma y restrict access of ol der a d olesce nts’ me dical rec or ds b y  t heir 
pare nt(s )/le gal g uar dia n i n certai n re gi o ns.
T he s o urce d oc u me ntati o n m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt, a n d as 
a p plica ble, asse nt was o btai ne d bef ore t he partici pa nt was e nr olle d i n t he st u d y  a n d t he date 
t he writte n c o nse nt/asse nt was o btai ne d. T he a ut h orize d pers o n o btai ni n g t he i nf or me d 
c o nse nt m ust als o si g n t he IC D.
Pare nt(s)/le gal g uar dia n a n d t he partici pa nt m ust be rec o nse nte d t o t he m ost c urre nt versi o n 
of t he I C D(s)/asse nt d uri n g t heir partici pati o n i n t he st u d y  as re q uire d per l ocal re g ulati o ns.
A c o p y of t he I C D(s) a n d asse nt, if writte n, m ust be pr o vi de d t o t he pare nt(s)/le gal 
g uar dia n a n d t he partici pa nt .
1 1. 4. D at a Pr otecti o n
All parties will c o m pl y  wit h all a p plica ble la ws, i ncl u di n g la ws re gar di n g t he i m ple me ntati o n 
of or ga ni zati o nal a n d tec h nical meas ures t o e ns ure pr otecti o n of partici pa nt data.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 4 9
Partici pa nt s’ pers o nal data will be st ore d at t he st u d y site i n e ncr ypte d electr o nic a n d/ or pa per 
f or m a n d will be pass w or d pr otecte d or sec ure d i n a l oc ke d r o o m t o e ns ure t hat o nl y  
a ut h orize d st u d y staff ha ve access. T he st u d y site will i m ple me nt a p pr o priate tec h nical a n d 
or ga nizati o nal meas ures t o e ns ure t hat t he pers o nal data ca n be rec o vere d i n t he e ve nt of 
disaster. I n t he e ve nt of a p ote ntial pers o nal data breac h, t he st u d y site will be res p o nsi ble f or 
deter mi ni n g w het her a pers o nal data breac h has i n fact occ urre d a n d, if s o, pr o vi di n g breac h 
n otificati o ns as re q uire d b y  la w.
T o pr otect t he ri g hts a n d free d o ms of partici pa nts wit h re gar d t o t he pr ocessi n g of pers o nal 
data, parti ci pa nts will be assi g ne d a si n gle, partici pa nt- s pecific n u merical c o de. A n y 
partici pa nt rec or ds or data sets t hat are tra nsferre d t o t he S p o ns or will c o ntai n t he n u merical 
c o de; partici pa nt na mes will n ot be tra nsferre d. All ot her i de ntifia ble data tra nsfe rre d t o t he 
S p o ns or will be i de ntifie d b y t his si n gle, partici pa nt -s pecific c o de. T he st u d y site will 
mai ntai n a c o nfi de ntial list of partici pa nts w h o partici pate d i n t he st u d y , li n ki n g eac h 
partici pa nt’s n u merical c o de t o t heir act ual i de ntit y  a n d me dical rec or d I D. I n case of data 
tra nsfer, t he S p o ns or will pr otect t he c o nfi de ntialit y of partici pa nts’ pers o nal data c o nsiste nt 
wit h t he cli nical st u d y a gree me nt a n d a p plica ble pri vac y  la ws.
I nf or mati o n tec h n ol o g y s yste ms use d t o c ollect, pr ocess, a n d st ore st u d y-relate d data are 
sec ure d by t ec h nical a n d or ga nizati o nal sec urit y meas ures desi g ne d t o pr otect s uc h data 
a gai nst acci de ntal or u nla wf ul l oss, alterati o n, or u na ut h orize d discl os ure or access.
T he S p o ns or mai ntai ns sta n dar d o perati n g pr oce d ures o n h o w t o res p o n d i n t he e ve nt of 
u na ut h orize d access, use, or discl os ure of S p o ns or i nf or mati o n or s y ste ms.
W he n partici pa nt data are t o be delete d, t he i n vesti gat or will e ns ure t hat all c o pies of s uc h 
data are pr o m ptl y  a n d irre v oca bly delete d fr o m all s y ste ms.
1 2. D A T A H A N D LI N G A N D R E C O R D K E E PI N G
1 2. 1. I ns pecti o n of Rec or ds
T he S p o n s or will be all o we d t o c o n d uct site visits t o t he i n vesti gati o n facilities f or t he 
p ur p ose of m o nit ori n g a n y  as pect of t he st u d y. T he I n vesti gat or a grees t o all o w t he m o nit or 
t o i ns pect t he dr u g st ora ge area, st u d y dr u g st oc ks, dr u g acc o u nta bilit y rec or ds, partici pa nt 
c harts, st u d y s o urce d oc u me nts, a n d ot her rec or ds relati ve t o st u d y c o n d uct.
T he I n vesti gat or a grees t o mai ntai n a Re g ulat or y  Bi n der i n a c urre nt, or ga nize d fas hi o n; t his 
Bi n der wil l c o ntai n d oc u me ntati o n s u p p orti ve of t he pr ot oc ol- a n d G C P -c o m plia nce of t he 
st u d y. T he c o ntents of t he Bi n der will be or ga nize d acc or di n g t o t he sta n dar ds of I C H E 6, 
Secti o n 8 ( Esse ntial D oc u me nts). T he I n vesti gat or a grees t o ma ke t his Bi n der accessi ble t o 
t he m o nit or, a u dit or, a n d re prese ntati ves of re g ulat or y a ge ncies a n d t he I R B/ E C.
1 2. 2. Rete nti o n of Rec or ds
T he I n vesti gat or will mai ntai n a de q uate rec or ds, i ncl u di n g partici pa nts’ me dical rec or ds, 
la b orat or y re p orts, si g ne d c o nse nt f or ms, dr u g acc o u nta bilit y rec or ds, safet y re p orts, 
i nf or mati o n re gar di n g partici pa nts w h o disc o nti n ue d t he pr ot oc ol, a n d a ny ot her perti ne nt 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 0
data. All st u d y  rec or ds m ust be retai ne d f or at least 2 years after t he last a p pr o val of a 
mar keti n g a p plicati o n i n t he U S A or a n I C H re gi o n a n d u ntil ( 1) t here are n o pe n di n g or 
c o nte m plate d mar keti n g a p plicati o ns i n t he U S A or a n I C H re gi o n or ( 2) at least 2 y ears ha ve 
ela pse d si nce t he f or mal disc o nti n uati o n of cli nical de vel o p me nt of t he i n vesti gati o nal 
pr o d uct u n der st u d y. T he I n vesti gat o r/i nstit uti o n s h o ul d retai n partici pa nt i de ntifiers f or at 
least 1 5 years after t he c o m pleti o n or disc o nti n uati o n of st u d y . St u d y partici pa nt files a n d 
ot her res o urce data m ust be ke pt f or t he ma xi m u m peri o d of ti me per mitte d b y  t he h os pital, 
i nstit uti o n but n ot less t ha n 1 5 ye ars. T hese d oc u me nts s h o ul d be retai ne d f or a l o n ger peri o d, 
if re q uire d by t he a p plica ble re g ulat or y re q uire me nts or b y  t he S p o ns or. T he S p o ns or m ust be 
n otifie d wit h rete nti o n s h o ul d t he I n vesti gat or/i nstit uti o n are u na ble t o c o nti n ue wit h t he 
mai nte na nce of st u d y  partici pa nt files f or t he f ull 1 5 years. All st u d y rec or ds m ust be st ore d 
i n a sec ure a n d safe facilit y. 
T he I n vesti gat ors m ust retai n pr ot oc ols, a me n d me nts, IR B/ I E C a p pr o vals, c o pies of t he F or m 
F D A 1 5 7 2, si g ne d a n d date d c o nse nt f or ms, me dical rec or ds, C R Fs, dr u g acc o u nta bilit y  
rec or ds, all c orres p o n de nce a n d a ny ot her d oc u me nts pertai ni n g t o t he c o n d uct of t he st u d y. 
If t he I n vesti gat or m o ves, wit h dra ws fr o m a n i n vesti gati o n or retires, t he res p o nsi bilit y f or 
mai ntai ni n g t he rec or ds ma y  be tra nsferre d t o a n ot her pers o n w h o will acce pt res p o nsi bilit y. 
N otice of tra nsfer m ust be ma de t o a n d a gree d b y t he S p o ns or. T he I n vesti gat or m ust n otif y  
t he S p o ns or i m me diatel y i n t he e ve nt of acci de ntal l oss or destr ucti o n of a n y pr otoc ol 
rec or ds.
1 2. 3. Discl os ure of I nf or m ati o n
Partici pa nts’ me dical i nf or mati o n o btai ne d as a res ult of t his st u d y  is c o nsi dere d c o nfi de ntial, 
a n d discl os ure t o t hir d parties ot her t ha n t h ose n ote d i n t his pr ot oc ol is pr o hi bite d. S u bject t o 
a p plica ble a ut h orizati o n(s), re p orts a n d c o m m u nicati o ns relati n g t o partici pa nts i n t his st u d y 
will i de ntif y  t h ose partici pa nts o nl y b y n u m ber a n d/ or i nitials. Partici pa nt’s me dical 
i nf or mati o n res ulti n g fr o m t his st u d y ma y be gi ve n t o t he partici pa nt’s pers o nal p h ysicia n, 
ot h er a ut h orize d parties, or t o t he a p pr o priate me dical pers o n nel res p o nsi ble f or t he 
partici pa nt wit h re gar d t o t his cli nical trial. Data ge nerate d i n t his st u d y  will be a vaila ble f or 
i ns pecti o n o n re q uest by t he F D A or ot her g o ver n me nt re g ulat or y a ge nc y a u dit ors, t he 
s p o ns or, t he s p o ns or’s Me dical M o nit or ( or desi g nee), a n d t heir desi g nate d re prese ntati ves, 
t he IR B/ E C, a n d ot her a ut h orize d parties. All i nf or mati o n c o ncer ni n g t he st u d y  me dicati o n 
a n d t he s p o ns or’s o perati o ns (s uc h as pate nt a p plicati o ns, f or m ulas, ma n ufact uri n g pr ocesses, 
basic scie ntific data, or ot her i nf or mati o n s u p plie d b y  t he S p o ns or a n d n ot pre vi o usl y 
p u blis he d) are c o nsi dere d c o nfi de ntial a n d s hall re mai n t he s ole pr o pert y of t he S p o ns or. T he 
I n vesti gat or a grees t o use t his i nf or mati o n o nl y  i n c o n d ucti n g t his st u d y a n d t o n ot use it f or 
ot her p ur p oses wit h o ut t he S p o ns or’s pri or writte n c o nse nt. T he i nf or mati o n de vel o pe d i n 
t his cli nical st u d y will be use d b y t he S p o ns or i n t he cli nical de vel o p me nt of v o xel ot or a n d 
t heref ore, ma y be discl ose d b y t he S p o ns or as re q uire d, t o a ut h orize d parties (i ncl u di n g its 
c or p orate part ners f or t he st u d y  dr u g, if a n y, a n d t heir desi g nate d re prese ntati ves), ot her 
cli nical I n vesti gat ors, p har mace utical c o m pa nies, t he F D A, a n d ot her g o ver n me nt a ge ncies. 
A n y i nf or mati o n, i n ve nti o ns, disc o veries ( w het her pate nta ble or n ot), i n n o vati o ns, 
s u g gesti o ns, i deas, a n d re p orts ma de or de vel o pe d b y t he I n vesti gat or(s) as a res ult of 
c o n d ucti n g t his st u d y s hall be pr o m ptl y discl ose d t o t he S p o ns or a n d s hall be t he s ole 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 1
p r o perty of t he S p o ns or. T he I n vesti gat or a grees, u p o n t he S p o ns or’s re q uest a n d at t he 
S p o ns or’s e x pe nse, t o e xec ute s uc h d oc u me nts a n d t o ta ke s uc h ot her acti o ns as t he s p o ns or 
dee ms necessar y  or a p pr o priate t o o btai n pate nts i n t he s p o ns or’s na me c o veri ng a n y of t he 
f ore g oi n g. 
1 2. 4. Disse mi n ati o n of Cli nic al St u d y D at a
T he S p o ns or f ulfills its c o m mit me nt t o p u blicl y  discl ose cli nical st u d y res ults t hr o u g h 
p osti n g t he res ults of st u dies o n w w w.cli nicaltrials. g o v ( Cli nical Trials. g o v), t he 
E u dra C T/ C TI S, a n d/ or w w w. pfizer.c o m, a n d ot her p u blic re gistries a n d we bsites i n 
acc or da nce wit h a p plica ble l ocal la ws/re g ulati o n. I n a d diti o n, t he S p o ns or re p orts st u d y  
res ults o utsi de of t he re q uire me nt of l ocal la ws/re g ulati o ns p urs ua nt t o its sta n dar d o perati n g 
pr oce d ures.
In all cases, st u d y  res ults are re p orte d by t he S p o ns or i n a n o bjecti ve, acc urate, bala nce d, a n d 
c o m plete ma n ner a n d are re p orte d re gar dless of t he o utc o me of t he st u d y or t he c o u ntr y i n 
w hic h t he st u d y  was c o n d ucte d.
w w w.cli nicaltrials. g o v
T he S p o ns or p osts cli nical trial res ults o n w w w.cli nicaltrials. g o v f or G B T/ Pfizer s p o ns ore d 
i nter ve nti o nal st u dies (c o n d ucte d i n patie nts) t hat e val uate t he safety a n d/ or efficac y of a 
pr o d uct, re gar dless of t he ge o gra p hical l ocati o n i n w hic h t he st u d y is c o n d ucte d. T hese 
res ults are s u b mitte d f or p osti n g i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h by U S 
la w.
E u dra C T/ C TI S
T he S p o ns or p osts cli nical trial res ults o n E u dra C T/ C TI S f or G B T/ Pfizer s p o ns ore d 
i nter ve nti o nal st u dies i n acc or da nce wit h t he f or mat a n d ti meli nes set f ort h b y E U 
re q uire me nts.
w w w. pfizer.c o m
T he S p o ns or p osts cli nical st u d y  re p ort ( C S R) s yn o pses a n d plai n -la n g ua ge st u d y res ults 
s u m maries o n w w w. pfizer.c o m f or G B T/ Pfizer s p o ns ore d i nter ve nti o nal st u dies at t he sa me 
ti me t he c orres p o n di n g stu d y  res ults are p oste d t o w w w.cli nicaltrials. g o v. C S R s yn o pses will 
ha ve pers o nall y  i de ntifia ble i nf or mati o n a n o n ymize d.
D oc u me nts wit hi n mar keti n g a p plicati o ns
T he S p o ns or c o m plies wit h a p plica ble l ocal la ws/re g ulati o ns t o p u blis h cli nical d oc u me nts 
i ncl ude d i n mar keti n g a p plicati o ns. Cli nical d oc u me nts i ncl u de s u m mar y  d oc u me nts a n d 
C S Rs i ncl u di n g t he pr ot oc ol a n d pr ot oc ol a me n d me nts, sa m ple C R Fs, a n d S A Ps. Cli nical 
d oc u me nts will ha ve pers o nall y  i de ntifia ble i nf or mati o n a n o n ymize d.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 2
Data s hari n g
T he S p o ns or pr o vi des researc hers sec ure access t o partici pa nt -le vel data or f ull C S Rs f or t he 
p ur p oses of “ b o na fi de scie ntific researc h” t hat c o ntri b utes t o t he scie ntific u n dersta n di n g of 
t he disease, tar get, or c o m p o u n d class. T he S p o ns or will ma ke data fr o m t hese trials a vaila ble 
1 8 m o nt hs after st u d y c o m pleti o n. Partici pa nt le vel data will be a n o n ymize d i n acc or da nce 
wit h a p plica ble pri vac y  la ws a n d re g ulati o ns. C S Rs will ha ve pers o nally i de ntifia ble 
i nf or mati o n a n o ny m ize d.
Data re q uests are c o nsi dere d fr o m q ua lifie d researc hers wit h t he a p pr o priate c o m pete ncies t o 
perf or m t he pr o p ose d a nal yses. Researc h tea ms m ust i ncl u de a bi ostatisticia n. Data will n ot 
be pr o vi de d t o a p plica n ts wit h si g nifica nt c o nflicts of i nterest, i ncl u di n g i n di vi d uals 
re q uesti n g access f or c o m mercial/c o m petiti ve or le gal p ur p oses.
1 2. 5. D at a Q u alit y Ass ur a nce
All partici pa nt data relati n g t o t he st u d y will be rec or de d o n pri nte d or electr o nic C R F u nless 
tra ns mitte d t o t he S p o ns or or desi g nee electr o nicall y (e g, la b orat or y data). T he I n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.
G ui da nce o n c o m pleti o n of C R Fs will be pr o vi de d i n t he C R F C o m pleti o n Re q uire me nt 
d oc u me nt.
T he I n vesti gat or m ust e ns ure t hat t he C R Fs are sec urel y st ore d at t he st u d y site i n e ncr y pte d 
electr o nic a n d/ or pa per f or m a n d are pass w or d - pr otecte d or sec ure d i n a l oc ke d r o o m t o 
pre ve nt access b y u na ut h orize d t hir d parties.
T he I n vesti gat or m ust per mit st u d y -relate d m o nit ori n g, a u dits, I R B/ E C re vie w, a n d 
re g ulat or y a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce rec or ds a n d d oc u me nts. 
T his verificati o n ma y  als o occ ur after st u d y c o m pleti o n. It is i m p orta nt t hat t he 
I n vesti gat or(s) a n d t heir rele va nt pers o n nel are a vaila ble d uri n g t he m o nit ori n g visits a n d 
p ossi ble a u dits or i ns pecti o ns a n d t hat s ufficie nt ti me i n de v ote d t o t he pr ocess.
M o nit ori n g details descri bi n g strate g y , i ncl u di n g defi niti o n of st u d y-critical data ite ms a n d 
pr ocesses (e g, ris k -base d i nitiati ves i n o perati o ns a n d q uali t y s uc h as ris k ma na ge me nt a n d 
miti gati o n strate gies a n d a nal yt ical ris k-base d m o nit ori n g), met h o ds, res p o nsi bilities, a n d 
re q uire me nts, i ncl u di n g ha n dli n g of n o nc o m plia nce iss ues a n d m o nit ori n g tec h ni q ues 
(ce ntral, virt ual, or o n-site m o nit ori n g), are pr ovi de d i n t he data ma na ge me nt pla n mai ntai ne d 
a n d utilize d b y t he S p o ns or or desi g nee.
T he S p o ns or or desi g nee is res p o nsi ble f or t he data ma na ge me nt of t his st u d y , i ncl u di n g 
q ualit y  c hec ki n g of t he data.
Rec or ds a n d d oc u me nts, i ncl u di n g si g ne d I C Fs, pertai ni n g t o t he c o n d uct of t his st u d y  m ust 
be retai ne d b y t he I n vesti gat or f or 1 5 ye ars after st u d y c o m pleti o n u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y be destr o ye d d uri n g 
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 3
t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he s p o ns or. N o rec or ds ma y be 
tra nsferre d t o a n ot her l ocati o n or party wit h o ut writte n n otificati o n t o t he S p o ns or. T he 
I n vesti gat or m ust e ns ure t hat t he rec or ds c o nti n ue t o be st ore d sec urely f or as l o n g as t he y are 
mai ntai ne d.
W he n partici pa nt data are t o be delete d, t he I n vesti gat or will e ns ure t hat all c o pies of s uc h 
data are pr o m ptl y  a n d irre v oca bly delete d fr o m all s yste ms.
T he I n vesti gat or(s) will n otif y  t he S p o ns or or its a ge nts i m me diately of a n y re g ulat or y 
i ns pecti o n n otificati o n i n relati o n t o t he st u d y. F urt her m ore, t he I n vesti gat or will c o o perate 
wit h t he S p o ns or or its a ge nts t o pre pare t he I n vesti gat or site f or t he i ns pecti o n a n d will all o w 
t he S p o ns or or its a ge nt, w he ne ver feasi ble, t o be prese nt d uri n g t he i ns pectio n. T he 
I n vesti gat or site a n d I n vesti gat or will pr o m ptl y res ol ve a n y discre pa ncies t hat are i de ntifie d 
bet wee n t he st u d y data a n d t he partici pa nt’s me dical rec or ds. T he I n vesti gat or will pr o m ptl y 
pr o vi de c o pies of t he i ns pecti o n fi n di n gs t o t he S p o ns or or its a ge nt. Bef ore res p o nse 
s u b missi o n t o t he re g ulat or y a ut h orities, t he I n vesti gat or will pr o vi de t he S p o ns or or its 
a ge nts wit h a n o p p ort u nit y t o re vie w a n d c o m me nt o n res p o nses t o a n y s uc h fi n di n gs. 
1 2. 6. St u d y a n d Site St art a n d Cl os ure
T he st u d y  start date is t he date of t he first partici pa nt’s first visit.
T he S p o ns or desi g nee reser ves t he ri g ht t o cl ose t he st u d y  site or ter mi nate t he st u d y at a ny 
ti me f or a ny reas o n at t he s ole discreti o n of t he S p o ns or, i ncl u di n g ( b ut n ot li mite d t o) 
re g ulat or y a ut h ority decisi o n, c ha n ge i n o pi ni o n of t he I R B/ E C, or c ha n ge i n be nefit -ris k 
assess me nt. St u d y sites will be cl ose d u p o n st u d y c o m pleti o n. A st u d y site is c o nsi dere d 
cl ose d w he n all re q uire d d oc u me nts a n d st u d y  s u p plies ha ve bee n c ollecte d a n d a st u d y-site 
cl os ure visit has bee n perf or me d.
T he I n vesti gat or ma y  i nitiate st u d y-site cl os ure at a n y ti me u p o n n otificati o n t o t he S p o ns or 
or desi g nee/ C R O if re q ueste d t o d o s o b y  t he res p o nsi ble IR B/ E C or if s uc h ter mi nati o n is 
re q uire d t o pr otect t he healt h of st u d y partici pa nts.
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he S p o ns or ma y i ncl u de b ut are n ot li mite d 
t o:

Fail ure of t he I n vesti gat or t o c o m pl y  wit h t he pr ot oc ol, t he re q uire me nts of t he 
I RB/ E C or l ocal healt h a ut h orities, t he S p o ns or’s pr oce d ures, or t he I CH G C P 
g ui deli nes;

I na de q uate recr uit me nt of partici pa nts b y  t he I n vesti gat or;

Disc o nti n uati o n of f urt her st u d y  i nter ve nti o n de vel o p me nt.
If t he st u d y is pre mat urel y ter mi nate d or s us pe n de d, t he S p o ns or s hall pr o m ptl y i nf or m t he 
I n vesti gat ors, t he E Cs/IR Bs, t he re g ulat or y  a ut h orities, a n d a n y C R O(s) use d i n t he st u d y of 
t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble re g ulat or y 
re q uire me nts. T he I n vesti gat or s hall pr o m ptl y i nf or m t he partici pa nt a n d s h o ul d ass ure 
a p pr o priate partici pa nt t hera py a n d/ or f oll o w - u p.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 4
St u d y  ter mi nati o n is als o pr o vi de d f or i n t he cli nical st u d y a gree me nt. If t here is a n y c o nflict 
bet wee n t he c o ntract a n d t his pr ot oc ol, t he c o ntract will c o ntr ol as t o ter mi nati o n ri g hts. 
1 3. P U B LI C A TI O N P O LI C Y
F or m ultice nter trials, t he pri mar y  p u blicati o n will be a j oi nt p u blicati o n de vel o pe d by t he 
I n vesti gat or a n d t he S p o ns or re p orti n g t he pri mar y e n d p oi nt(s) of t he st u d y c o veri n g all st u d y 
sites. T he I n vesti gat or a grees t o refer t o t he pri mar y p u blicati o n i n a ny s u bse q ue nt 
p u blicati o ns. T he S p o ns or will n ot pr o vi de a n y fi na ncial c o m pe nsati o n f or t he I n vesti gat or’s 
partici pati o n i n t he pre parati o n of t he pri mar y  c o n gress a bstract, p oster, prese ntati o n, or 
pri mar y  ma n uscri pt f or t he st u d y.
I n vesti gat ors are free t o p u blis h i n di vi d ual ce nter res ults t hat t he y dee m t o be cli nicall y 
mea ni n gf ul after p u blicati o n of t he o verall res ults of t he st u d y  or 1 2 m o nt hs after pri mar y 
c o m pleti o n date or st u d y c o m pleti o n at all sites, w hic he ver occ urs first, s u bject t o t he ot her 
re q uire me nts descri be d i n t his secti o n.
T he I n vesti gat or will pr o vi de t he S p o ns or a n o p p ort u nit y  t o re vie w a ny pr o p ose d p u blicati o n 
or a n y ot her t y pe of discl os ure of t he st u d y res ults (c ollecti vel y, “ p u blicati o n”) bef ore it is 
s u b mitte d or ot her wise discl ose d a n d will s u b mit all p u blicati o ns t o t he S p o ns or 3 0 da y s 
bef ore s u b missi o n. If a n y pate nt acti o n is re q uire d t o pr otect i ntellect ual pr o pert y ri g hts, t he 
I n vesti gat or a grees t o dela y t he discl os ure f or a peri o d n ot t o e xcee d a n a d diti o nal 6 0 da ys 
u p o n re q uest fr o m t he S p o ns or. T his all o ws t he S p o ns or 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, a n d t he I n vesti gat or will, o n re q uest, re m o ve a n y pre vi o usl y 
u n discl ose d c o nfi de ntial i nf or mati o n bef ore discl os ure, e xce pt f or a n y st u d y i nter ve nti o n or 
S p o ns or relate d i nf or mati o n necessar y  f or t he a p pr o priate scie ntific prese ntati o n or 
u n dersta n di n g of t he st u d y  res ults. F or j oi nt p u blicati o ns, s h o ul d t here be disa gree me nt 
re gar di n g i nter pretati o n a n d/ or prese ntati o n of s pecific a nalys is res ults, res ol uti o n of, a n d 
res p o nsi bilit y f or, s uc h disa gree me nts will be t he c ollecti ve res p o nsi bilit y of all a ut h ors of 
t he p u blicati o n.
F or all p u blicati o ns relati n g t o t he st u d y, t he i n vesti gat or a n d t he S p o ns or will c o m pl y wit h 
rec o g nize d et hical sta n dar ds c o ncer ni ng p u blicati o ns a n d a ut h ors hi p, i ncl u di n g t h ose 
esta blis he d b y t he I nter nati o nal C o m mittee of Me dical J o ur nal E dit ors. T he I n vesti gat or will 
discl ose a n y relati o ns hi p wit h t he S p o ns or a n d a n y rele va nt p ote ntial c o nflicts of i nterest, 
i ncl u di n g a ny fi na ncial or pers o nal relati o ns hi p wit h t he S p o ns or, i n a n y  p u blicati o ns. All 
a ut h ors will ha ve access t o t he rele va nt statistical ta bles, fi g ures, a n d re p orts (i n t heir ori gi nal 
f or mat) re q uire d t o de vel o p t he p u blicati o n.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 5
1 4. R E F E R E N C E S
1.
He b bel R P. Rec o nstr ucti n g si c kle cell disease: a data -base d a nal ys is of t he 
“ h yper he m ol ys is para di g m” f or p ul m o nar y h yperte nsi o n fr o m t he pers pecti ve of 
e vi de nce -base d me dici ne. A m J He mat ol. 2 0 1 1; 8 6: 1 2 3 - 1 5 4
2.
H o war d J, He m ma wa y  CJ, Telfer P, La yt o n D M, P orter J, A w o g ba de M, et al. A 
p hase 1/ 2 asce n di n g d ose st u d y  a n d o pe n-la bel e xte nsi o n st u d y of v o xel ot or i n 
patie nts wit h sic kle cell disease. Bl o o d. 2 0 1 9; 1 3 3( 1 7): 1 8 6 5 - 1 8 7 5.
3.
R ot her R P, Bell L , Hill me n, P a n d Gla d wi n M T. T he cli nical se q uelae of 
i ntra vasc ular he m ol ysis a n d e xtracell ular plas ma he m o gl o bi n. J A M A 2 0 0 5, 
2 9 3: 1 6 5 3 - 1 6 6 2.
4.
Vic hi ns k y  E, H o p pe C C, Ata ga KI, Ware R E, N d u ba V, El-Bes hla w y  A. et al. A 
p hase 3 ra n d o mize d trial of v o xel ot or i n sic kle cell disease. N E n gl J Me d. 
2 0 1 9; 3 8 1: 5 0 9 - 5 1 9.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 6
1 5. A P P E N DI C E S
A p pe n di x 1. Sc he d ule of assess me nts
Assess me nts
Tre at me nt Peri o d
E n d of St u d y i
St u d y D a y(s)
D a y 
1 a
W 4 *
± 5 
d a ys
W 8 *
± 5 
d a ys
W 1 2
± 5 
d a ys
W 2 4
± 1 0 
d a ys
W 3 6
± 1 0 
d a ys
W 4 8
± 1 0 
d a ys
Q 1 2
W ks
± 1 0 
d a ys
Q 2 4
W ks
± 1 0 
d a ys
I nf or me d C o nse nt / Asse nt
X
Eli gi bilit y Assess me nt
X
Me dical Hist or y 
X
P h ysical E xa mi nati o n b
X  
X  
X  
X  
X
X
X  
X
Vital Si g ns c
X  
X  
X  
X  
X
X
X
A d verse E ve nts
X  
X  
X  
X  
X
X
X  
X
C o nc o mita nt Me dicati o ns
X  
X  
X  
X  
X
X
X  
X
He mat ol o g y/ C he mistr y a nal yze d 
b y Ce ntral La b orat or y 
( U S a n d E ur o pe o nl y) d
X  
X  
X  
X  
X
X
X
He mat ol o g y/ C he mistr y a nal yze d 
b y L ocal La b orat or y 
(e x-U S a n d e x -E ur o pe o nl y) d , e
X
a
X  
X  
X  
X
X
X f
X
E x pl orat or y La b orat or y 
 
 ( U S a n d E ur o pe O nl y) 
X
X  
X
X
Uri ne Pre g na nc y Test   g
X  
X  
X  
X  
X
X
X  
X
Dr u g Dis pe nsi n g a n d 
Acc o u nta bilit y h
X
X  
X  
X  
X  
X  
X  
X
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)
C CI

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
Pa ge 5 7
Assess me nts
Tre at me nt Peri o d
E n d of St u d y i
St u d y D a y(s)
D a y 
1 a
W 4 *
± 5 
d a ys
W 8 *
± 5 
d a ys
W 1 2
± 5 
d a ys
W 2 4
± 1 0 
d a ys
W 3 6
± 1 0 
d a ys
W 4 8
± 1 0 
d a ys
Q 1 2
W ks
± 1 0 
d a ys
Q 2 4
W ks
± 1 0 
d a ys
A b bre viati o ns: Q = e ver y; W = w ee k; W ks = wee ks
* 
Partici pa nts fr o m G B T 4 4 0 -0 3 1 w h o recei ve d G B T 4 4 0 9 0 0 m g or place b o, or w h o recei ve d v o xel ot or f or less t ha n 1 2 wee ks will ha ve a d diti o nal 
assess me nts at Wee k 4 a n d Wee k 8.
a.
Eli gi bilit y assess me nts will be deter mi ne d o n Da y 1 pri or t o d osi n g. If la bs were d o ne f or G B T 4 4 0 -0 3 1 or t his st u d y wit hi n 7 da ys of Da y 1, t he y d o 
n ot nee d t o be re peate d o n Da y 1.
b. 
A b bre viate d P h ysical E xa m w hic h i ncl u des: ge neral a p peara nce, e xa mi nati o n of e yes, s ki n, car di o vasc ular a n d res pirat or y s yste ms, a n a b d o mi nal 
e xa mi nati o n a n d a s y m pt o m directe d e xa mi nati o n. 
c. 
Vital si g ns ( heart rate [ H R], bl o o d press ure [ B P]) w ill be c ollecte d after a partici pa nt has reste d f or at least 5 mi n utes i n t he seate d or s u pi ne p ositi o n. 
A re peate d meas ure me nt of H R a n d B P w ill be ta ke n if t he first rea di n g is o utsi de t he n or mal ra n ge a n d dee me d cli nicall y si g nifica nt.
d. 
H e m at ol o g y assess me nts will i ncl u de: re d bl o o d cell ( R B C), he mat ocrit ( Hct), he m o gl o bi n ( H b), platelets, w hite bl o o d cell ( W B C), 
% retic ul oc ytes, a bs ol ute retic ul oc ytes, R B C distri b uti o n wi dt h ( R D W), mea n c or p usc ular v ol u me ( M C V) a n d mea n c or p usc ular he m o gl o bi n 
c o nce ntrati o n ( M C H C). After Wee k 4 8, he mat ol o g y assess me nts s h o ul d o nl y be perf or me d per sta n dar d of care.
e. 
Ser u m c he mistries will i ncl u de: Ala ni ne a mi n otra nsferase ( A L T), al kali ne p h os p hatase ( A L K), as partate a mi n otra nsferase ( A S T), bicar b o nate, B U N, 
creati ni ne, L D H, s o di u m, p otassi u m, bilir u bi n (t otal, direct, a n d i n direct). After Wee k 4 8, ser u m c he mistries s h o ul d o nl y be perf or me d per sta n dar d of 
care.
f. 
After Wee k 4 8 (f or partici pa nts e nr olle d o utsi de of t he U nite d States a n d E ur o pe), la b orat or y val ues f or meas ures of he m ol ysi s s uc h as he m o gl o bi n, 
% retic ul oc ytes, a bs ol ute retic ul oc ytes, a n d bilir u bi n (t otal, direct, a n d i n direct) w ill be c ollecte d e ver y 2 4 wee ks.
g. 
If a uri ne pre g na nc y test is p ositi ve, t he res ult m ust be c o nfir me d per l ocal sta n dar d of care (e g, ultras o u n d or ser u m pre g na nc y test).
h. 
V o xel ot or w ill be dis pe nse d i n 1 2-we e k ( ~ 9 0 da y) i nter vals wit h i nstr ucti o n t o partici pa nts t o ret ur n a n y use d/ u n use d b ottles t o cli nic.
i. 
T he E n d of St u d y ( E O S) visit s h o ul d be c o n d ucte d w it hi n 2 8-3 5 da ys after last d ose of st u d y dr u g f or partici pa nts w h o wit h dra w  fr o m t he st u d y 
earl y.  
T he E O S visit ca n occ ur a n y ti me after partici pa nts o btai ns c o m mercial v o xel ot or f or partici pa nts w h o c o m plete st u d y per pr ot oc ol. Partici pa nts w h o 
c o m plete st u d y per pr ot oc ol s h o ul d re mai n o n st u d y dr u g u ntil E O S visit is c o m plete d.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
P a ge 5 8
A p pe n di x 2. LI V E R S A F E T Y: S U G G E S T E D A C TI O N S A N D F O L L O W U P 
A S S E S S M E N T S 
P ote nti al C ases of Dr u g I n d uce d Li ver I nj ur y
H u ma ns e x p ose d t o a dr u g w h o s h o w n o si g n of li ver i nj ur y  (as deter mi ne d b y ele vati o ns i n 
tra nsa mi nases) are ter me d “t olerat ors,” w hile t h ose w h o s h o w tra nsie nt li ver i nj ur y b ut a da pt 
are ter me d “a da pt ors.” I n so me partici pa nts, tra nsa mi nase ele vati o ns are a har bi n ger of a 
m ore seri o us p ote ntial o utc o me. T hese partici pa nts fail t o a da pt a n d t heref ore are 
“s usce pti ble” t o pr o gressi ve a n d seri o us li ver i nj ur y , c o m m o nly referre d t o as DI LI. 
Partici pa nts w h o e x perie nce a tra nsa mi nase ele vati o n a b o ve 3 × t he u p per li mit of n or mal 
( U L N) s h o ul d be m o nit ore d m ore fre q ue ntl y t o deter mi ne if t he y are “a da pt ors” or are 
“s usce pti ble.”
Li ver f u ncti o n tests ( L F Ts) are n ot re q uire d as a r o uti ne safet y m o nit ori n g pr oce d ure i n t hi s 
st u d y. H o we ver, s h o ul d a n i n vesti gat or dee m it necessar y t o assess L F Ts beca use a 
partici pa nt prese nts wit h cli nical si g ns/s y m pt o ms, s uc h L F T res ults s h o ul d be ma na ge d a n d 
f oll o we d as descri be d bel o w.
I n t he maj orit y of DI LI cases, ele vati o ns i n A S T (as partate tra nsa mi nase) a n d/ or A L T 
(ala ni ne tra nsa mi nase) prece de t otal bilir u bi n ele vati o ns ( > 2 × U L N) by se veral da ys or 
wee ks. T he i ncrease i n t otal bilir u bi n t y picall y  occ urs w hile A S T/ A L T is/are still ele vate d 
a b o ve 3 × U L N (ie, A S T/ A LT a n d t otal bilir u bi n val ues will be ele vate d wit hi n t he sa me 
la b orat or y sa m ple). I n rare i nsta nces, b y t he ti me t otal bilir u bi n ele vati o ns are detecte d, 
A S T/ A L T val ues mi g ht ha ve decrease d. T his occ urre nce is still re gar de d as a p ote ntial DI LI. 
T heref ore, a b n or mal ele vati o ns i n eit her A S T or A L T i n a d diti o n t o t otal bilir u bi n t hat meet 
t he criteria o utli ne d bel o w are c o nsi dere d p ote ntial DI LI (assesse d per H y’s la w criteria) 
cases a n d s h o ul d al wa y s be c o nsi dere d i m p orta nt me dical e ve nts, e ve n bef ore all ot her 
p ossi ble ca use s of li ver i nj ur y ha ve bee n e xcl u de d.
T he t hres h ol d of la b orat or y  a b n or malities f or a p ote ntial DI LI case de pe n ds o n t he 
partici pa nt’s i n di vi d ual baseli ne val ues a n d u n derl yi n g c o n diti o ns. Partici pa nts w h o prese nt 
wit h t he f oll o wi n g la b orat or y  a b n or malities s h o ul d be e val uate d f urt her as p ote ntial DI LI 
( Hy’s la w) cases t o defi niti vel y  deter mi ne t he eti ol o g y of t he a b n or mal la b orat or y val ues:

Partici pa nts wit h A S T/ A L T a n d t otal bilir u bi n val ues wit hi n t he n or mal ra n ge 
w h o s u bse q ue ntl y  prese nt wit h A S T/ A LT va l ues ≥ 3 × U L N A N D a t otal 
bilir u bi n val ue ≥2 × U L N wit h n o e vi de nce of he m ol y sis a n d a n al kali ne 
p h os p hatase val ue < 2 × U L N or n ot a vaila ble.

F or partici pa nts wit h baseli ne A S T O R A L T O R t otal bilir u bi n val ues a b o ve t he 
U L N, t he f oll o wi n g t hres h ol d val u es are use d i n t he defi niti o n me nti o ne d a b o ve, 
as nee de d, de pe n di n g o n w hic h val ues are a b o ve t he U L N at baseli ne:

Pree xisti n g A S T/ A L T baseli ne val ues a b o ve t he n or mal ra n ge: A S T/ A L T 
val ues ≥ 2 ti mes t he baseli ne val ues A N D ≥ 3 × U L N; or ≥ 8 × U L N 
( w hic he ver is s maller).
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

Pr ot oc ol N u m ber ( G B T 4 4 0 -0 3 4/ C 5 3 4 1 0 2 2) 
Gl o bal Bl o o d T hera pe utics, I nc. a w h oll y o w ne d s u bsi diar y of Pfizer, I nc.
1 8 Dece m ber 2 0 2 3
A me n d me nt 3
P FI Z E R C O N FI D E N TI A L
P a ge 5 9

Pree xisti n g val ues of t otal bilir u bi n a b o ve t he n or mal ra n ge: t otal bilir u bi n 
le vel i ncrease d fr o m baseli ne val ue by a n a m o u nt of ≥ 1 × U L N or if t he val ue 
reac hes ≥ 3 × U L N ( w hic he ver is s maller).
Rises i n A S T/ A L T a n d t otal bilir u bi n se par ate d b y m ore t ha n a fe w wee ks s h o ul d be assesse d 
i n di vi d uall y base d o n cli nical j u d g me nt; a n y case w here u ncertai nt y re mai ns as t o w het her it 
re prese nts a p ote ntial H y’s la w case s h o ul d be re vie we d wit h t he s p o ns or. 
T he partici pa nt s h o ul d ret ur n t o t he i n vesti gat or site a n d be e val uate d as s o o n as p ossi ble, 
prefera bl y wit hi n 4 8 h o urs fr o m a ware ness of t he a b n or mal res ults. T his e val uati o n s h o ul d 
i ncl u de la b orat or y tests, detaile d hist or y, a n d p h ysical assess me nt. 
I n a d diti o n t o re peati n g meas ure me nts of AS T a n d A L T a n d t otal bilir u bi n f or s us pecte d 
H y ’s la w cases, a d diti o nal la b orat or y tests s h o ul d i ncl u de al b u mi n, creati ne ki nase, direct a n d 
i n direct bilir u bi n, ga m ma-gl uta m yl  tra nsferase, pr ot hr o m bi n ti me/i nter nati o nal n or malize d 
rati o, e osi n o p hils ( %), an d al kali ne p h os p hatase. C o nsi derati o n s h o ul d als o be gi ve n t o 
dra wi n g a se parate t u be of cl otte d bl o o d a n d a n a ntic oa g ulate d t u be of bl o o d f or f urt her 
testi n g, as nee de d, f or f urt her c o nte m p ora ne o us a nal yses at t he ti me of t he rec o g nize d i nitial 
a b n or mali ties t o deter mi ne eti ol o g y. A detaile d hist or y, i ncl u di n g rele va nt i nf or mati o n, s uc h 
as re vie w of et ha n ol, aceta mi n o p he n/ paraceta m ol (eit her b y itself or as a c of or m ulate d 
pr o d uct i n prescri pti o n or o ver -t he-c o u nter me dicati o ns), recreati o nal dr u g, or s u p ple me nt 
( her bal) use a n d c o ns u m pti o n, fa mil y hist or y, se x ual hist or y, tra vel hist or y, hist or y of c o ntact 
wit h a ja u n dice d pers o n, s ur ger y , bl o o d tra nsf usi o n, hist or y of li ver or aller gic disease, a n d 
p ote ntial occ u pati o nal e x p os ure t o c he micals, s h o ul d be c ollecte d. F urt her testi n g f or ac ute 
he patitis A, B, C, D, a n d E i nfecti o n, t otal bile aci ds, li ver i ma gi n g (e g, biliar y  tract), a n d 
c ollecti o n of ser u m sa m ples f or aceta mi n o p he n/ paraceta m ol dr u g a n d/ or pr otei n a d d uct 
le vels ma y be warra nte d. 
All cases de m o nstrate d o n re peat testi n g as meeti n g t he la b orat or y  criteria of A S T/ A LT a n d 
t otal bilir u bi n ele vati o n defi ne d a b o ve s h o ul d be c o nsi dere d p ote ntial DI LI ( Hy’s la w) cases 
if n o ot her reas o n f or t he L F T a b n or malities has yet bee n f o u n d. S uc h p ote nti al DI LI ( H y’s 
l a w) c ases are t o be re p orte d as S A Es, irres pecti ve of a v ail a bilit y of all t he res ults of t he 
i n vesti g ati o ns perf or me d t o deter mi ne eti ol o g y of t he L F T a b n or m alities.
A p ote ntial DI LI ( H y ’s la w) case bec o mes a c o nfir me d case o nly after all res ults o f 
reas o na ble i n vesti gati o ns ha ve bee n recei ve d a n d ha ve e xcl u de d a n alter nati ve eti ol o g y.
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)

D o c u m e nt A p pr o v al R e c or d
D o c u m e nt N a m e:
D o c u m e nt Titl e:
Si g n e d B y:
D at e( G M T)
Si g ni n g C a p a cit y
0 9 0 1 7 7 e 1 9f b d cff 7\ A p pr o v e d\ A p pr o v e d O n: 2 4- J a n- 2 0 2 4 2 1: 3 5 ( G M T)
P P D
P P D