A Multicenter, Multiple-Dose Study in Neovascular Age-related Macular Degeneration (nAMD) to Evaluate the Safety, Tolerability, Pharmacodynamics, Immunogenicity, and Clinical Effect of Repeat Intravitreal (IVT) Injections of GEM103 as an Adjunct to Standard of Care Aflibercept Therapy
Phase: PHASE2
Conditions: Neovascular Age-related Macular Degeneration, Retinal Disease, Retinal Degeneration, Macular Degeneration
Sponsor: Gemini Therapeutics, Inc.

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R MI S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C.  
 
A M ultice nter, M ulti ple- D os e St u d y i n Ne o v asc ul ar A ge-rel ate d M ac ul ar De ge ner ati o n 
( n A M D) t o E v al u ate t h e S afet y, T oler a bilit y, P h ar m a c o d y n a mics, I m m u n o ge nicit y, a n d 
Cli nic al Effect of Re pe at I ntr a vitre al (I V T) I njecti o ns of G E M 1 0 3 as a n A dj u nct t o 
St a n d ar d of C are Afli berce pt T her a p y 
 
Pr ot oc ol N u m ber: 
G E M- C L- 1 0 3 1 1 
D ate of Pr ot oc ol: 
5 Ma y 2 0 2 1 
Pr ot oc ol V ersi o n: 
Versi o n 3. 0  
( P)I N D N u m ber: 
1 4 1 0 3 6 
Pr o d uct: 
Rec o m bi na nt H u ma n C o m ple me nt Fact or H ( G E M 1 0 3) 
I n dic ati o n: 
Ne o vasc ular A ge-rel ate d Mac ular De ge n erati o n 
S p o ns or: 
Ge mi ni T hera p e utics, I nc. 
3 0 0 O ne Ke n d all S q uare, 3 r d Fl o or 
Ca m bri d ge, M A 0 2 1 3 9, U S A  
T he st u d y will be c o n d ucte d acc or di n g t o t he I nter n at i o n al C o u ncil f or H ar m o nis ati o n tri p artite g ui deli ne 
E 6( R 2): G o o d Cli nic al Pr actice   
 
 
 
T H E C O N C E P T S A N D I N F O R M A TI O N C O N T AI N E D  I N T HI S D O C U M E N T O R G E N E R A T E D 
D U RI N G T H E S T U D Y A R E C O N SI D E R E D P R O P RI E T A R Y A N D M A Y N O T B E DI S C L O S E D I N 
W H O L E O R I N P A R T WI T H O U T T H E E X P R E S S W RI T T E N C O N S E N T O F G E MI NI T H E R A P E U TI C S, 
I N C. 

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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
C O N T E N T S 
C O N T E N T S....................................................................................................................... ........... ii 
LI S T O F T A B L E S ................................................................................................................ ..... vii 
LI S T O F FI G U R E S ............................................................................................................... ... viii 
A P P R O V A L SI G N A T U R E P A G E ........................................................................................... i x  
I N V E S TI G A T O R S T A T E M E N T .............................................................................................. x 
LI S T O F A B B R E VI A TI O N S .................................................................................................... xi  
C LI NI C A L S T U D Y S Y N O P SI S ............................................................................................. xiii 
1  
I N T R O D U C TI O N.......................................................................................................... 2 0 
1. 1  
B ac k gr o u n d ........................................................................................................ 2 0  
1. 1. 1  
Disease .................................................................................................. 2 0  
1. 1. 2  
Me dical Rati o nale f or G E M 1 0 3 ........................................................... 2 1  
1. 2  
I n vesti g ati o n al Me dici n al Pr o d uct ( G E M 1 0 3) ................................................ 2 2 
1. 3  
N o ncli nic al S u m m ar y ........................................................................................ 2 2  
1. 4  
Cli nic al S u m m ar y .............................................................................................. 2 4  
1. 5  
D ose R ati o n ale a n d Ris k/ Be nefits ..................................................................... 2 4  
1. 5. 1  
St u d y D ose Rati o nale............................................................................ 2 4  
1. 5. 2  
Ris k/ Be nefit Assess me nt f or St u d y Dr u g a n d St u d y 
Pr oce d ures .............................................................................................  2 5  
2  
S T U D Y O B J E C TI V E S A N D E N D P OI N T S ................................................................  2 8  
3  
I N V E S TI G A TI O N A L P L A N ....................................................................................... 3 0 
3. 1  
O ver all Desi g n a n d Pl a n of t he St u d y .............................................................. 3 0  
3. 2  
St u d y Desi g n a n d Criteri a f or D osi n g .............................................................. 3 0  
3. 3  
R ati o n ale f or St u d y Desi g n ............................................................................... 3 1  
3. 4  
R ati o n ale f or D ose .............................................................................................. 3 2  
3. 5  
St u d y E n d p oi nts ................................................................................................. 3 2  
4  
S T U D Y P O P U L A TI O N ................................................................................................ 3 3  
4. 1  
T ar get P o p ul ati o n .............................................................................................. 3 3  
4. 2  
N u m ber of S u bjects ............................................................................................ 3 3 
4. 3  
Eli gi bilit y Criteri a .............................................................................................. 3 3  
4. 3. 1  
I ncl usi o n Criteria .................................................................................. 3 3 
4. 3. 2  
E xcl usi o n Criteria ................................................................................. 3 3  
4. 4  
Met h o d f or Assi g ni n g S u bjects t o Tre at me nt Gr o u ps.................................... 3 5  
4. 5  
S u bject Restricti o ns D u ri n g t he St u d y ............................................................. 3 5  

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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
4. 5. 1  
Ge neral a n d Dietar y .............................................................................. 3 5  
4. 5. 2  
C o ntrace pti o n a n d Pre g na nc y A v oi da nce P r oce d ures .......................... 3 5 
4. 6  
C o nc o mit a nt Me dic ati o ns a n d Tre at me nts ..................................................... 3 5  
4. 7  
Disc o nti n u ati o n of S u bjects ............................................................................... 3 6  
4. 7. 1  
Pre mat ure Wit h dra wal fr o m St u d y Partici pati o n.................................. 3 6  
4. 7. 2  
Pr oce d ures f or Disc o nti n uati o n ............................................................ 3 6  
4. 8  
S u bject Re pl ace me n t P olic y .............................................................................. 3 6 
4. 9  
S u bject Res cree ni n g ........................................................................................... 3 6 
5  
S T U D Y P R O C E D U R E S ............................................................................................... 3 7  
5. 1  
St u d y Assess me nts ............................................................................................. 3 7  
5. 1. 1  
I nf or me d C o nse nt ................................................................................. 3 7 
5. 1. 2  
Ge netic Sa m ple C ollecti o n ................................................................... 3 7  
5. 1. 3  
Me dical a n d Oc ular Hist or y .................................................................. 3 7  
5. 1. 4  
De m o gra p hic I nf or mati o n..................................................................... 3 7  
5. 1. 5  
P h ysical E xa mi nati o n ........................................................................... 3 7  
5. 1. 6  
O p ht hal mic  E xa mi nati o n ...................................................................... 3 8  
5. 1. 7  
Vital Si g n Meas ure me nts ...................................................................... 3 8  
5. 2  
Cli nic al L a b or at or y Assess me nts ..................................................................... 3 8  
5. 2. 1  
D N A Sa m p le ......................................................................................... 3 8 
5. 2. 2  
E x pl orat or y Bi o mar kers ........................................................................ 3 9  
5. 2. 3  
P K a n d I m m u n o ge nicit y Assess me nts .................................................. 3 9  
5. 3  
I m a gi n g Assess me nts ......................................................................................... 3 9 
5. 4  
Deter mi n ati o n of St u d y E ye .............................................................................. 4 0  
6  
S T U D Y T R E A T M E N T S ............................................................................................... 4 1  
6. 1  
Tre at me nts A d mi nistere d  ................................................................................. 4 1 
6. 1. 1  
D ose A dj ust me nts ................................................................................. 4 1  
6. 1. 2  
D ose Escalati o n..................................................................................... 4 1  
6. 2  
St o p pi n g R ules .................................................................................................... 4 1  
6. 2. 1  
St o p pi n g R ules i n I n di vi d ual S u bjects .................................................. 4 1  
6. 2. 2  
St o p pi n g R ules f or M ulti ple S u bjects ................................................... 4 1  
6. 3  
Descri pti o n of St u d y Dr u g................................................................................. 4 1  
6. 4  
St or a ge a n d Dis p ositi o n of St u d y Dr u g ............................................................ 4 1  
6. 4. 1  
Recei pt of Dr u g S u p plies ...................................................................... 4 1  

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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
6. 4. 2  
Ma na ge me nt of Cli nical S u p plies ......................................................... 4 2  
6. 4. 3  
St ora ge .................................................................................................. 4 2  
6. 4. 4  
Dis p ositi o n ............................................................................................ 4 2  
6. 5  
Pre p ar ati o n a n d A d mi nistr ati o n of St u d y Dr u g ............................................. 4 2  
6. 5. 1  
Pre parati o n of St u d y Dr u g .................................................................... 4 2  
6. 5. 2  
A d mi nistrati o n of St u d y Dr u g .............................................................. 4 3  
6. 6  
R a n d o miz ati o n of t he St u d y Dr u g .................................................................... 4 3  
6. 7  
Destr ucti o n of t he St u d y Dr u g .......................................................................... 4 4  
7  
A S S E S S M E N T O F S A F E T Y ........................................................................................ 4 5  
7. 1  
A Es a n d L a b or at or y A b n or m alities ................................................................. 4 5  
7. 1. 1  
Cli nical A Es .......................................................................................... 4 5  
7. 1. 2  
La b orat or y Test A b n or malit y ............................................................... 4 6  
7. 2  
Rec or di n g of A Es ............................................................................................... 4 7  
7. 3  
Re p orti n g a n d H a n dli n g of S afet y P ar a meters ............................................... 4 7  
7. 3. 1  
S A Es (I m me diatel y Re p orta ble t o t he S p o ns or) ................................... 4 7  
7. 3. 2  
A E Re p orti n g Peri o d ............................................................................. 4 7  
7. 3. 3  
I n vesti gat or Re p orti n g:  N otif yi n g t he S p o ns or .................................... 4 8 
7. 3. 4  
I n vesti gat or Re p orti n g:  N otif yi n g t he I R B/I E C................................... 4 8 
7. 3. 5  
S p o ns or Re p orti n g:  N otif yi n g Re g ulat or y A ut h orities ........................ 4 8  
7. 3. 6  
S p o ns or Re p orti n g:  N otif yi n g Partici pati n g I n vesti gat ors................... 4 8  
7. 3. 7  
Treat me nt a n d F oll o w- u p of A Es ......................................................... 4 8  
7. 3. 8  
F oll o w- u p of A b n or mal La b orat or y Test Val ues ................................. 4 9  
7. 3. 9  
Pre g na nc y.............................................................................................. 4 9  
7. 4  
Me dic al Re vie w C o m mittee ( M R C) ................................................................. 4 9  
8  
S T A TI S TI C A L P L A N ................................................................................................... 5 0  
8. 1  
Ge ner al C o nsi der ati o ns ..................................................................................... 5 0  
8. 2  
Deter mi n ati o n of S a m ple Size ........................................................................... 5 0  
8. 3  
A n al ysis Sets ....................................................................................................... 5 0  
8. 3. 1  
C o nse nte d S u bject Set .......................................................................... 5 0  
8. 3. 2  
Bi o mar ker Set ....................................................................................... 5 0  
8. 3. 3  
F ull A nal ysis Set ................................................................................... 5 0  
8. 4  
De m o gr a p hics a n d S afet y A n al ysis .................................................................. 5 0  
8. 5  
Bi o m ar ker, I m a gi n g, a n d Cli nic al E n d p oi nt A n al ysis ................................... 5 1  

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
8. 6  
S u m m aries of D at a Pri or t o St u d y C o m pleti o n .............................................. 5 1  
8. 6. 1  
Ha n dli n g of Missi n g Data ..................................................................... 5 2  
9  
D A T A Q U A LI T Y A N D A S S U R A N C E, S U B J E C T 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 ........................................................................................... 5 3  
9. 1  
S o urce D oc u me nts .............................................................................................. 5 3  
9. 2  
C ase Re p ort F or ms ( C R Fs) ............................................................................... 5 3  
9. 3  
Rec or ds Rete nti o n .............................................................................................. 5 3  
1 0  
S T U D Y M O NI T O RI N G, A U DI TI N G, A N D I N S P E C TI N G .................................... 5 4  
1 0. 1  
St u d y M o nit ori n g Pl a n ...................................................................................... 5 4  
1 0. 2  
A u diti n g a n d I ns pecti n g .................................................................................... 5 4  
1 0. 3  
M a n a ge me nt of Pr ot oc ol A me n d me nts a n d De vi ati o ns ................................. 5 4  
1 0. 3. 1  
M o dificati o n of t he Pr ot oc ol ................................................................. 5 4  
1 0. 3. 2  
Pr ot oc ol De viati o ns............................................................................... 5 4  
1 0. 4  
St u d y Ter mi n ati o n ............................................................................................. 5 5  
1 1  
I N V E S TI G A T O R O B LI G A TI O N S ............................................................................. 5 6 
1 1. 1  
C o nfi de nti alit y .................................................................................................... 5 6  
1 1. 2  
I nstit uti o n al Re vie w ........................................................................................... 5 6 
1 1. 3  
S u bject C o nse nt .................................................................................................. 5 6  
1 1. 4  
Fi n a nci al Discl os ure a n d O bli g ati o ns............................................................... 5 6  
1 1. 5  
St u d y C o n d uct a n d A d here nce t o Pr ot oc ol ..................................................... 5 7  
1 1. 6  
D at a C ollecti o n ................................................................................................... 5 7  
1 1. 7  
Re p orti n g A d verse E ve nts ................................................................................. 5 7  
1 1. 8  
Rec or ds Rete nti o n .............................................................................................. 5 7  
1 1. 9  
P u blic ati o ns ........................................................................................................ 5 7  
1 2  
E T HI C A L C O N SI D E R A TI O N S .................................................................................. 5 8  
1 3  
C LI NI C A L S T U D Y R E P O R T A N D D A T A DI S C L O S U R E .................................... 5 9  
1 3. 1  
Fi n al Re p ort ........................................................................................................ 5 9  
1 4  
R E F E R E N C E S ............................................................................................................... 6 0  
1 5  
A P P E N DI C E S ................................................................................................................ 6 3  
A p pe n di x A:  Sc he d ule of Assess me nts ........................................................................ 6 4  
A p pe n di x B:  Bi ol o gic al S a m ple C ollecti o n a n d S hi p pi n g I nstr ucti o ns.................... 6 7  
A p pe n di x C:  C ol or F u n d u s P h ot o gr a p h y ( C F P) ....................................................... 6 8 
A p pe n di x D:  F u n d us A ut ofl u oresce nce ( F A F) ........................................................... 6 9  
A p pe n di x E:  Fl u orescei n A n gi o gr a p h y ( F A) .............................................................. 7 0  

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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
A p pe n di x F:  S pectr al D o m ai n O ptic al C o here nce T o m o gr a p h y ( S D-
O C T).................................................................................................................... 7 1  
A p pe n di x G:  O ptic al C o here nce T o m o gr a p h y – A n gi o gr a m ( O C T- A) .................. 7 2  
A p pe n di x H:  Ne ar I nfr are d Reflect a nce I m a gi n g ( NI R) .......................................... 7 3  
A p pe n di x I:  Mi n nes ot a L o w- visi o n Re a di n g Test ( M N Re a d) C h arts...................... 7 4  
A p pe n di x J:  N ati o n al E ye I nstit ute Vis u al F u ncti o ni n g Q uesti o n n aire 
2 5-ite m Versi o n ( N EI- V F Q- 2 5) wit h Ne ar a n d Dist a nce Acti vit y 
S u bsc ale Sc ores................................................................................................... 7 6  
A p pe n di x K:  Gr a di n g Sc ale f or U veitis ...................................................................... 8 8  
A p pe n di x L:  Me dic ati o ns K n o w n t o P ote nti all y E x acer b ate M ac ul ar 
E de m a or M ac ul ar De ge ner ati o n ..................................................................... 8 9  
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
LI S T O F T A B L E S 
T a ble 1.  
St u d y O bjecti v es a n d E n d p oi nts ..................................................................................... 2 8  
T a ble 2.  
Assess me nt of Ca usalit y ................................................................................................ 4 6  
 

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5 Ma y 2 0 2 1 
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
LI S T O F FI G U R E S 
Fi g ure 1  
St u d y Desi g n ..................................................................................................................  3 1 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 9 of 8 9 
G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R MI S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C.  
A P P R O V A L SI G N A T U R E P A G E 
Pr ot oc ol Title: 
A M ultice nter, M ulti ple- D ose St u d y i n Ne o v asc ul ar A ge- Relate d 
Mac ular De ge n erati o n ( n A M D) t o E val uate t h e Safet y, 
T olera bilit y, P har m ac o d y na mics, I m m u n o ge nicit y, a n d Cli nical 
Effect of Re peat I ntra vitreal (I V T) I njecti o ns of G E M 1 0 3 as a n 
A dj u nct t o Sta n dar d of Care Afli berce pt T hera p y  
Pr ot oc ol N u m ber: 
G E M- C L- 1 0 3 1 1 
Pr ot oc ol V ersi o n: 
Versi o n 3. 0 
D ate of Pr ot oc ol: 
5 Ma y 2 0 2 1 
 
R E VI E W E D/ A P P R O V E D B Y: 
 
 
 
S p o ns or a p pr o val  
 
Si g nat ure 
Date              
Title of s p o ns or a p pr o ver 
 
 
 
P P D
P P D
P P D

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
I N V E S TI G A T O R S T A T E M E N T 
I a gree t o c o n d uct t his cli nical st u d y i n acc or da nce wit h t he desi g n a n d s pecific pr o visi o ns of t his 
pr ot oc ol. 
I u n dersta n d t hat I ma y ter mi nate or s us pe n d e nr oll me nt i n t he st u d y at a n y ti me if it bec o mes 
necessar y t o pr otect t he best i nte rests of t he st u d y s u bjects.  T his st u d y ma y be ter mi nate d at a n y 
ti me b y t he S p o ns or, wit h or wit h o ut ca use. 
I a gree t o pers o nall y c o n d uct a n d s u per vise t his i n vesti gati o n at m y i nstit uti o n a n d t o e ns ure t hat 
all ass ociates, c ollea g ues, a n d e m pl o yees assisti n g i n t he c o n d uct of t his st u d y are i nf or me d 
a b o ut t heir o bli gati o ns i n meeti n g t hese c o m mit me nts. 
I will c o n d uct t he st u d y i n acc or da nce wit h G o o d Cli nical Practice, t he Declarati o n of Helsi n ki, 
a n d t he m oral, et hical, a n d scie ntific pri nci ples t hat j ustif y me dical researc h.  T he st u d y will be 
c o n d ucte d i n acc or da nce wit h all rele va nt la ws a n d re g ulati o ns relati n g t o cli nical st u dies a n d t he 
pr otecti o n of s u bjects.   
I will e ns ure t hat t he re q uire me nts relati n g t o I nstit uti o nal Re vie w B oar d/I n de pe n de nt Et hics 
C o m mittee (I R B/I E C) re vie w a n d a p pr o val are met.  I will pr o vi de t he S p o ns or wit h a n y 
material t hat is pr o vi de d t o t he I R B/I E C f or et hical a p pr o val. 
I a gree t o mai ntai n a de q uate a n d acc urate rec or ds a n d t o ma ke t h ose rec or ds a vaila ble f or a u dit 
a n d i ns pecti o n i n acc or da nce wit h rele va nt re g ulat or y re q uire me nts. 
I a gree t o pr o m ptl y re p ort t o t he I R B/I E C a n y c ha n ges i n t he researc h acti vit y a n d all 
u na ntici pate d pr o ble ms i n v ol vi n g ris ks t o h u ma n s u bjects or ot hers.  A d diti o nall y, I will n ot 
ma ke a n y c ha n ges i n t he researc h wit h o ut I R B/I E C a n d S p o ns or a p pr o val, e xce pt w here 
necessar y t o e ns ure t he safet y of st u d y s u bjects. 
 
 
 
I n vesti gat or Na me  
  I n vesti gat or Si g nat ure  
  
Date 
 
 
I n vesti gati o nal site or na me of i nstit uti o n  
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
LI S T O F A B B R E VI A TI O N S 
A b b re vi ati o n
 Defi niti o n
 
A D A
 a nti dr u g
 
a nti b o d y(ies)
 
A E(s)
 a d v erse
 
e v e nt(s)
 
A M D
 a g e-relat e d
 
mac ular
 
d e g e n erati o n
 
A P
 alter n ati v e
 
p at h wa y
 
A U C
 are a
 
u n d er
 
c ur v e
 
B C V A 
b est c orre cte d vis u al a c uit y 
B L A
 Bi ol o gics
 
Lice nse
 
A p plicati o n
 
C F H
 c o m ple me nt
 
fact or
 
H
 
C F R
 C o d e
 
of
 
F e d eral
 
R e g ulati o ns
 
CI
 c o nfi d e n ce
 
i nter v al
 
C ma x  ma xi m u m
 c o n ce ntrati o n
 
C N V
 c h or oi d al
 
n e o v asc ulari zati o n
 
C P T 
ce nter p oi nt t hic k ness 
C S R
 cli nic al
 
st u d y
 
re p ort
 
C S T 
ce ntral s u bfiel d t hic k ness 
E C G
 ele ctr o car di o gra m
 
e C R F  
ele ctr o nic case r e p ort f or m 
E O M
 e v er y
 
ot h er
 
m o nt h
 
E O S  
e n d of st u d y 
E T D R S  
E arl y Treat me nt Dia b eti c R eti n o p at h y St u d y 
E U
 E ur o pea n
 
U ni o n
 
F A
 fl u oresc ei n
 
a n gi o gra p h y
 
F A F
 f u n d us
 
a ut ofl u oresce n ce
 
F A S  
F ull A nal ysis Set 
F D A  
F o o d a n d Dr u g A d mi nistrati o n 
G A
 g e o gra p hic
 
atr o p h y
 
G C P
 G o o d
 
Cli nical
 
Practi ce
 
G L P  
G o o d L a b orat or y Practice 
I C F
 i nf or me d
 
c o nse nt
 
f or m
 
I C H  
I nter n ati o n al C o u n cil f or H ar m o nisati o n 
I E C
 I n de pe n de nt
 
Et hics
 
C o m mittee
 
I O P
 i ntra o c ular
 
press ure
 
I R B
 I nstit uti o n al
 
Re vie w
 
B o ar d
 
I V T
 i ntra vitr eal
 
L L V A  
l o w l u mi n a n ce vis u al ac uit y 
M A
 m ac ular
 
atr o p h y
 
Me d D R A  
Me dical Dicti o n ar y f or Re g ulat or y Acti vities 
M N Rea d  
Mi n n es ota L o w- visi o n Rea di n g Test 
M R C
 Me dical
 
Re vie w
 
C o m mittee
 
n A M D  
N e o v asc ular A g e- R elate d Mac ular D e g e n erati o n 
N EI- V F Q- 2 5  
Nati o n al E y e I nstit ute Vis u al F u n cti o ni n g Q uesti o n n aire- 2 5 

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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
A b b re vi ati o n
 Defi niti o n
 
NI R  
n ear i nfrare d reflecta n ce i m a gi n g 
O C T
 o ptical
 
c o h ere n ce
 
t o m o gra p h y
 
O C T- A 
o ptical c o h ere n ce t o m o gra p h y – a n gi o gra m/a n gi o gra p h y 
P D
 p h ar mac o d y n a mic(s)
 
P K
 p h ar mac o ki n etic(s)
 
P T
 preferre d
 
ter m
 
r h C F H 
rec o m bi n a nt h u ma n C F H 
R P E 
reti n al pi g me nt e pit h eli u m 
S A E(s)
 seri o us
 
a d v ers e
 
e v e nt(s)
 
S A P 
Statistic al A n al ysis Pla n 
S D- O C T 
s p ectr al d o mai n o ptical c o h ere n c e t o m o gra p h y 
S O A
 sc h e d ule
 
of
 
assess me nts
 
S o C
 sta n d ar d
 
of
 
care
 
S O C
 s yste m
 
or g a n
 
class
 
T E A E 
treat me nt-e m er g e nt a d v erse e v e nt 
U S 
U nite d States ( of A meric a) 
V A
 vis u al
 
ac uit y
 
V E G F 
v asc ular e n d ot h elial gr o wt h fact or 
 
 

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5 Ma y 2 0 2 1 
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
C LI NI C A L S T U D Y S Y N O P SI S 
P r ot o c ol Title 
A M ultice nter, M ulti ple- D ose St u d y i n N e o v asc ular A g e-r elate d Mac ular 
De ge nerati o n ( n A M D) t o E val uate t h e Safet y, T olera bilit y, P har mac o d y na mics, 
I m m u n o g e nicit y, a n d Cli nical Effect of Re p eat I ntra vitr eal (I V T) I njecti o ns of 
G E M 1 0 3 as a n A dj u n ct t o Sta n d ar d of C are Afli b er ce pt T h era p y 
P r ot o c ol N u m b er 
G E M- C L- 1 0 3 1 1 
Cli nic al P h ase 
P h ase 2 a 
( P)I N D N u m ber 
1 4 1 0 3 6 
I n dic ati o n 
N e o v asc ular A g e- R elate d Mac ular D e g e n erati o n 
O bjecti v es a n d 
E n d p oi nts 
T h e pri mar y e n d p oi nt will assess t h e s afet y a n d t olera bilit y of 
G E M 1 0 3 +sta n d ar d of care ( S o C) vs s h a m + S o C ( S o C is d efi n e d as afli b er ce pt 
e v er y ot h er m o nt h [ E O M]) t hr o u g h 1 2 m o nt hs.  S ec o n d ar y a n d e x pl orat or y 
e n d p oi nts will ass ess G E M 1 0 3 + S o C vs s h a m + S o C at m o nt h 1 2 a n d o v er ti m e. 
O bjecti v es
 E n d p oi nts
 
P ri m a r y 
 
 
Descri b e t h e saf et y a n d t olera bilit y 
of G E M 1 0 3 + S o C vs s h a m + S o C 
 
O c ular a n d n o n- o c ular 
treat me nt-e m er g e nt 
a d v erse e v e nts ( T E A Es) 
 
C h a n g es i n o p ht h al mic 
e x a ms 
 
R es ults of vis u al f u n cti o n 
ass ess m e nts 
 S ec o n d a r y
 
 
 
T o e v al u ate t otal c o m ple me nt 
fact or H ( C F H) i n a q u e o us h u m or 
after G E M 1 0 3 I V T i njecti o n, 
w h e n e v er p ossi ble 
 
A q u e o us h u m or c o n ce ntrati o ns of 
t otal C F H  
 
 
Descri b e t h e eff ect o n b est 
c orrecte d vis u al ac uit y ( B C V A) 
 
Mea n c h a n g e i n B C V A fr o m 
b aseli n e i n Earl y Treat m e nt 
Dia b etic R eti n o p at h y St u d y 
( E T D R S) letters 
 
 
Descri b e t h e eff ect o n mac ular 
atr o p h y ( M A) size i n s u bjects wit h 
M A prese nt at b aseli n e 
 
Mea n c h a n ge i n size of M A 
e v al u ate d b y f u n d us 
a ut ofl u oresce n c e ( F A F)  
 
E x pl o r at o r y 
 
 
T o e v al u ate t h e i m m u n o g e nicit y of 
G E M 1 0 3 i n ser u m after G E M 1 0 3 
I V T i njecti o n, w h e n e v er p ossi ble 
 
Ge n er ati o n of ser u m G E M 1 0 3 
a nti dr u g a nti b o dies 
 
 
D escri b e t h e eff ect of G E M 1 0 3 
I V T i njecti o n o n bi o mar k ers i n 
a q u e o us h u m or 
 
C h a n g e fr o m b aseli n e i n 
c o m ple me nt pr otei n, c o m ple m e nt 
s plit pr o d u cts, a n d relate d 
c yt o ki n es pr otei n v al u es i n 
a q u e o us h u m or 

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5 Ma y 2 0 2 1 
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
 
 
D escri b e t h e eff ect o n i n ci d e n ce of 
ne w M A i n s u bjects wit h o ut M A 
at b aseli n e 
 
Ne w M A e v al uate d b y F A F  
 
 
D escri b e t h e eff ect o n c h or oi d al 
n e o v asc ulariz ati o n ( C N V) size 
 
Mea n re d u cti o n fr o m b aseli n e i n 
C N V size as e v al u at e d b y 
fl u oresc ei n a n gi o gra p h y ( F A) 
 
 
D escri b e t h e eff ect o n t hic k n ess of 
reti n al la y ers 
 
Mea n c h a n g e fr o m b aseli n e i n 
ce nter p oi nt t hic k n ess a n d ce ntral 
s u bfiel d t hic k n ess i n μ m as 
e v al u ate d b y s p ectral d o mai n 
o ptical c o h ere n ce t o m o gra p h y 
( S D- O C T) 
 
 
D escri b e t h e eff ect o n s u breti n al 
a n d i ntrareti n al fl ui d 
 
T h e pr o p orti o n of p atie nts wit h 
i ntrar eti n al or s u breti n al fl ui d as 
e v al u ate d b y S D- O C T 
 
 
Descri b e t h e eff ect o n l o w 
l u mi na nce vis u al ac uit y ( L L V A) 
 
Mea n c h a n g e i n L L V A fr o m 
b aseli n e i n E T D R S letters 
 
 
D escri b e t h e eff ect o n N ati o n al 
E y e I nstit ute Vis u al F u n cti o ni n g 
Q u esti o n n aire 2 5 ite m V ersi o n 
( N EI- V F Q- 2 5)  
 
D escri b e t h e eff ect o n Mi n n es ota 
L o w- visi o n Rea di n g Test 
( M N Rea d) 
 
Mea n c h a n g e i n sc ore fr o m 
b aseli n e o n N EI- V F Q- 2 5  
 
Mea n c h a n g e i n ma xi m u m rea di n g 
s p ee d fr o m b aseli n e o n M N Rea d 
Test 
Met h o d ol o g y 
Ge mi ni T h era p e utics, I n c. (t h e S p o ns or) is d e v el o pi n g G E M 1 0 3 (rec o m bi n a nt 
h u ma n c o m ple me nt fact or H [r h C F H]) as a n alter n ati v e pat h wa y ( A P) 
c o m ple m e nt m o d ulat or y t h era p y f or t h e treat m e nt of n e o v asc ular a g e-rel ate d 
mac ular de ge nerati o n ( n A M D).  G E M 1 0 3 is bei n g de vel o pe d t o rest ore 
a p pr o priate re g ulati o n of t h e c o m ple m e nt s yste m i n n A M D p atie nts. 
G E M 1 0 3 is i nte n de d t o be use d as a n A P c o m ple me nt m o d ulat or y t h era p y f or 
t h e treat me nt of n A M D b y pr o vi di n g s u pra p h ysi ol o gical r h C F H b y I V T 
i njecti o n. 
T his is a P h ase 2 a, si n gle- mas k e d, s h a m-c o ntr olle d, m ultice nter, m ulti ple- d ose 
st u d y i n s u bjects wit h n A M D t o e v al u ate t h e safet y, t oler a bilit y, 
i m m u n o ge nicit y, p h ar mac o ki netic/ p har mac o d y na mic, c o m ple me nt bi o mar k ers, 
a n d cli nical effe ct d uri n g 1 2 m o nt hs of G E M 1 0 3 I V T i njecti o ns E O M as a n 
a dj u n ct t o S o C afli b erce pt t h era p y. 
St u d y dr u g or s h a m, al o n g wit h S o C afli b erce pt, will be a d mi nistere d t o 1 e y e 
o nl y, w hic h will b e d esi g n ate d d uri n g t h e scre e ni n g pr o cess, b ase d o n 
eli gi bilit y, a n d pri or t o a n y baseli ne meas ure me nts.  If b ot h e y es meet all e y e-
s p ecific e ntr y criteria, t h e n t h e st u d y e y e will b e d eter mi n e d b y t h e I n v esti g at or 
a n d t h e s u bject t o g et h er.  All assess me nts will b e p erf or me d i n t h e st u d y e y e as 
well as t h e f ell o w e y e w h e n e v er feasi ble. 
Detail e d ass ess m e nts of i ntra o c ular press ure (I O P), vis u al ac uit y ( V A) a n d 
f u n cti o n, a n d reti n al p ara met ers s u c h as C N V a n d M A lesi o n size will b e 
p erf or me d f or eac h s u bject e nr olle d. 

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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
D ata will b e c olle ct e d o n d e m o gra p hics, m e dical a n d o c ular hist or y, fa mil y 
hist or y, a n d c o n c o mita nt m e dicati o ns.  A d diti o n all y, o p ht h al mic a n at o mic 
ass ess m e nts a n d m ulti m o d al i ma gi n g, e x pl orat or y g e n etic a n d bi o mar k er 
a n al yses, a n d a q u e o us h u m or sa m pli n g will b e d o n e f or eac h s u bject e nr olle d. 
T h e I n v esti g at or will m o nit or t h e safet y of st u d y pr o ce d ures acc or di n g t o l o cal 
i nstit uti o n al p olic y.  All A Es will b e rec or d e d i n t h e electr o nic cas e re p ort f or m.  
Acc u m ulati n g safet y data will be re vie we d o n a n o n g oi n g basis. 
St u d y D u r ati o n 
T h e mi ni m u m pla n n e d d urati o n of eac h s u bject’s p artici p ati o n is a p pr o xi matel y 
1 3 m o nt hs:  1 m o nt h f or scree ni n g a n d 1 2 m o nt hs f or d osi n g a n d f oll o w- u p. 
St u d y C e nters 
It is a nti ci p at e d t h at a p pr o xi matel y 4 0 st u d y ce nters will p arti ci p ate i n t his 
st u d y. 
N u m b er of S u bjects 
Pl a n n e d 
A p pr o xi matel y 4 5 s u bjects ( ~ 3 0 treate d wit h G E M 1 0 3 + S o C a n d ~ 1 5 treate d 
wit h s h a m + S o C) are pla n n e d f or i n cl usi o n i n t h e st u d y. 
I n cl usi o n a n d 
E x cl usi o n Criteri a 
I ncl usi o n Criteri a: 
S u bjects m ust meet all of t h e f oll o wi n g i n cl usi o n criteri a t o be c o nsi d ere d f or 
p artici p ati o n: 
1.  At least 5 0 y ears ol d at t h e ti me of si g n e d i nf or me d c o nse nt; s u bjects 
y o u n g er t h a n 5 0 m a y b e c o nsi d ere d f or p artici p ati o n after c o ns ultati o n 
wit h t h e Me dical M o nit or 
2.  C N V relate d t o n A M D wit h t h e f oll o wi n g feat ures, as d eter mi n e d b y t h e 
I ma g e R ea di n g C e nter 
a. Ma xi m u m C N V lesi o n size of 1 2 disc areas 
b.  
 
3.   M ust b e o n afli b erce pt tr eat me nt pri or t o Da y 1 ( wit h at least o n e 
afli b erce pt d ose re cei v e d wit hi n 2 m o nt hs pri or t o D a y 1) A N D b e a ble 
t o c o nti n u e afli b erce pt at a n e v er y- ot h er- m o nt h fre q u e n c y f or t h e 
d urati o n of t h e st u d y 
4.  B C V A i n t h e st u d y e y e of 2 4 t o 7 5 letters usi n g t h e E T D R S C h art V A 
S cale ( a p pr o xi m atel y e q ui v ale nt t o S n elle n V A of b et wee n 2 0/ 3 2 a n d 
2 0/ 3 2 0) 
5.  S ufficie ntl y cl ear o c ular m e di a, a d e q u ate p u pillar y dilati o n, fi x ati o n t o 
p er mit q u alit y f u n d us i ma gi n g, a n d a ble t o c o o p erate s uffi ci e ntl y f or 
a d e q u ate o p ht h al mic vis u al f u n cti o n testi n g a n d a n at o mic assess me nt i n 
t h e st u d y e y e 
6.  U n d ersta n ds t h e f ull n at ure a n d p ur p ose of t h e st u d y, i n cl u di n g p ossi ble 
ris ks of st u d y pr o ce d ures, a n d pr o vi d es i nf or me d c o nse nt pri or t o 
i nitiati o n of a n y st u d y pr o ce d ure 
7.  All s u bjects wit h re pr o d u cti v e p ote ntial m ust a gree t o use eff ecti v e 
c o ntrace pti v e m et h o ds t hr o u g h t h e e n d of st u d y ( E O S) visit. 
E x cl usi o n C riteri a: 
A s u bject w h o meets a n y of t h e f oll o wi n g e x cl usi o n criteria will b e i n eli gi ble t o 
p artici p ate: 
1.  Prese n ce of t h e f oll o wi n g o c ular c o n diti o ns i n t he st u d y e y e: 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
a. A n y acti v e o c ular dise as e or c o n diti o n t h at c o ul d c o nf o u n d t h e 
ass ess m e nt of t h e mac ula or b e a c o ntrai n dicati o n t o I V T i njecti o n, 
e. g., reti nal pi g me nt e pit h eli u m tears or ri ps i n v ol vi n g t h e mac ula, 
mac ular h ole (a n y sta g e, i n cl u di n g la mellar h ole), e pireti n al 
me m bra n e, M A or mac ul o p at hies d u e t o a n y dise ase ot h er t h a n 
A M D, u nc o ntr olle d gla u c o ma (I O P of > 2 4 m m H g w he n o n 2 or 
m ore I O P-l o w eri n g me dicati o ns), se v ere gla u c o ma (c u p t o disc rati o 
0. 8), dia b etic reti n o p at h y gra d e d as m o d erate n o n pr oliferati v e 
dia b etic r eti n o p at h y or w orse ( wit h or wit h o ut dia b etic m ac ular 
e d e ma) 
b.  A n y i ntra o c ular s ur g er y, e. g., a n y gla u c o ma s ur g eries i n cl u di n g 
micr oi n v asi v e gla u c o m a s ur g er y a n d/ or a n y i ntra o c ular s ur g er y 
re q uiri n g vitrect o m y.  H o we v er, sta ble i ntra o c ular le ns re pl ace m e nt 
s ur g er y t h at was p erf or me d m ore t h a n 3 m o nt hs pri or t o c o nse nt will 
be all o we d. 
c. A p h a kia or c o m plete a bse n ce of t h e p osteri or ca ps ule 
d.  Pri or c or n eal tra ns pla nt 
e. 
 
2.  Prese n ce of a n y of t h e f oll o wi n g o c ular c o n diti o ns – i n eit h er e y e: 
a. Hist or y of h er p etic i nfecti o n, i di o p at hic p ol y p oi d al c h or oi d al 
v asc ul o p at h y ( P C V), p at h ol o gic m y o pia, ce ntral ser o us 
c h ori oreti n o p at h y ( C S C R), a d ult- o nset f o v eal p atter n d ystr o p h y 
b.  C o n c urre nt disease t h at c o ul d re q uire me dical or s ur gical 
i nter v e nti o n d uri n g t h e st u d y p eri o d 
c. Acti v e/s us p e cte d o c ular/ p eri o c ular i nfe cti o n or acti v e i ntr a o c ular 
i nfla m mati o n 
d.  Hist or y of i di o p at hic or a ut oi m m u n e-ass o ci ate d u v eitis 
3.  I n t h e o pi ni o n of t h e I n v esti g at or, t h e s u bject h as a n y pri or or o n g oi n g 
me dical c o n diti o n (e. g., oc ular ot her t h a n wet A M D, s yste mic, 
ps y c hiatric) or cli nic all y si g nific a nt scr ee ni n g la b orat or y v al u e t h at m a y 
prese nt a safet y ris k, i nterfere wit h st u d y c o m plia n ce, i nterf er e wit h 
c o nsiste nt st u d y f oll o w- u p, or c o nf o u n d d ata i nter pretati o n t hr o u g h o ut 
t h e l o n git u di n al f oll o w- u p p eri o d 
4.  S u bject h as e x p erie n ce d a car di o v as c ular or c ere br o v asc ular e v e nt wit hi n 
1 2 m o nt hs of i nf or me d c o nse nt 
5.  F e m ale s u bjects m ust n ot b e pre g n a nt or lactati n g, n or pla n t o b ec o m e 
pre g n a nt d uri n g t h e st u d y 

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5 Ma y 2 0 2 1 
Pa ge 1 7 of 8 9 
G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
6.  C urre nt use of m e dicati o ns k n o w n t o b e t o xic t o t h e le ns, reti n a, or o ptic 
n er v e ( d efer o x a mi n e, c hl or o q ui n e/ h y dr o x y c hl or o q ui n e [ Pla q u e nil ®], 
ta m o xife n, p h e n ot hiazi n es, et h a m b ut ol, di g o xi n, a n d a mi n o gl y c osi d es).  
( C urre nt use is d efi n e d as t h e a d mi nistrati o n of first d ose of G E M 1 0 3 
wit hi n 5 h alf-li v es of t h e pr o hi bite d me dicati o n).  P ast use of t h ese 
m e dicati o ns, wit h o ut hist or y of o c ular si d e eff ects, is n ot c o nsi d ere d 
e x cl usi o n ar y.  Use of me dicati o ns t h at ma y p ote ntiall y e x acer b ate 
m ac ular e d e ma or m ac ular d e g e n erati o n is p er mitte d if, i n t h e o pi ni o n of 
t h e I n v esti g at or, i n c o ns ultati o n wit h t h e Me dical M o nit or, s u c h use will 
n ot c o nf o u n d t h e i nter pretati o n of st u d y res ults 
7.  Use of a n y i n v esti g ati o n al n e w dr u g or ot h er e x p eri m e ntal tre at me nt i n 
t h e last 6 m o nt hs, a n d/ or recei pt at a n y ti m e of a n y pri or g e n e t h era p y 
(e. g., A d e n o-ass o ciat e d vir us), cell t h er a p y, or oc ular de vice 
i m pla ntati o n ( ot h er t h a n p osteri or c h a m b er i ntra o c ular l e ns place me nt 
after catar act s ur g er y) 
I n v esti g ati o n al 
P r o d u ct ( a n d 
Refer e n ce T her a p y), 
D ose, R o ute, 
Re gi me n 
G E M 1 0 3 (r h C F H) will b e s u p plie d i n si n gle- use vials wit h a 0. 2 5 m L fill 
v ol u m e at a c o n ce ntrati o n of 1 0 m g/ m L r h C F H. 
Afli b erc e pt a d mi nister e d I V T E O M is S o C t hera p y.  S u bjects assi g n e d t o t h e 
G E M 1 0 3 + S o C gr o u p w ill b e a d mi nistere d afli b erce pt ( 2 m g/ 5 0 μ L) first, 
f oll o we d b y G E M 1 0 3 ( 5 0 0 μ g/ 5 0 μ L) 1 5 mi n utes ( ± 5 mi n utes) lat er.  St u d y 
dr u g m ust n ot be mi xe d i n t h e sa me s yri n ge wit h ot her pr o d ucts. 
S u bjects will b e ra n d o mize d t o 1 of 2 treat me nt gr o u ps:  G E M 1 0 3 + S o C or 
s h a m + S o C.  S u bjects ra n d o mize d t o t h e G E M 1 0 3 + S o C treat me nt gr o u p will 
rec ei v e tr eat me nt E O M ( 6 d oses).  All s u bjects assi g n e d t o t h e G E M 1 0 3 + S o C 
treat me nt will b e tre at e d wit h 5 0 0 μ g G E M 1 0 3 p er e y e. 
S u bjects ra n d o mize d t o t h e s h a m + S o C treat me nt gr o u p will recei v e S o C wit h a 
s h a m I V T i njecti o n i nstea d of G E M 1 0 3, t o k ee p t h e s u bject mas k e d t o t h eir 
treat me nt assi g n me nt. 
St atistic al Met h o ds  
Ge ner al C o nsi der ati o ns 
D escri pti v e s u m m ar y statisti cs will b e pr o vi d e d f or d e m o gra p hics, dis p ositi o n, 
a n d d ose e x p os ure.  T h e n u m b er a n d p erce nta g e of s u bjects w h o disc o nti n u e d 
fr o m t h e st u d y, al o n g wit h reas o ns f or disc o nti n u ati o ns, will b e ta b ulate d a n d 
d escri b e d i n listi n gs.  All d escri pti v e s u m mari es will b e pr o vi d e d b y treat me nt 
gr o u p ( G E M 1 0 3 vs s h a m). 
C o nti n u o us d ata will b e s u m m arize d usi n g d escri pti v e statistics ( n u m b er of 
s u bjects, mea n, sta n dar d de viati o n, me dia n, mi ni m u m, a n d ma xi m u m) a n d, 
w h ere a p pr o priate, gra p hic re prese nt ati o n, a n d t w o-
i nter v als ( CI); c ate g oric al d ata will b e s u m marize d b y sa m ple size, pr o p orti o ns, 
a n d t w o-
 
A n y re p orte d p- val u es will be c o nsi d ere d part of t h e descri pti v e a n al yses (i. e., 
h y p ot h esis- g e n erati n g) a n d will n ot b e a dj uste d f or m ulti plicit y.  T h e p hrase 
“st atistic all y si g nifi ca nt” ma y b e use d i nterc h a n g ea bl y wit h “ n o mi n all y 
statisticall y si g nific a nt” t o i n dicate t h at a n o mi n al p-
 

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5 Ma y 2 0 2 1 
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
S a m ple Size 
T h e pla n n e d t otal sa m ple siz e of a p pr o xi matel y 4 5 s u bjects ( ~ 3 0 treat e d wit h 
G E M 1 0 3 + S o C, ~ 1 5 treate d wit h s h a m + S o C) is b ase d o n feasi bilit y 
c o nsi d erati o ns, rat h er t h a n a n y s p ecifi c st atisti cal t est. 
A n al ysis S ets 
T h e C o nse nte d S u bject S et will i n cl u d e s u bjects w h o si g n e d t h e i nf or me d 
c o nse nt f or m a n d will be use d t o create a dia gra m t o ill ustrate s u bject fl o w fr o m 
c o nse nt t hr o u g h dis p ositi o n (si milar t o a C o ns oli d ate d Sta n d ar ds of R e p orti n g 
Trials [ C O N S O R T] dia gra m f or a ra n d o mize d trial). 
T he Bi o mar ker Set will i n cl u de s u bjects wit h s ufficie nt data t o assess bi o m ar k er 
res ults. 
T h e F ull A n al ysis S et ( F A S) will i n cl u d e all s u bjects w h o recei v e at l east 1 
d ose of st u d y dr u g/refere n c e t h era p y ( G E M 1 0 3 or s h a m).  S afet y a n al yses will 
be perf or me d o n t h e F A S.  A nal yses o n t h e F A S are c o nsiste nt wit h t h e 
i nte nti o n-t o-treat pri n ci ple. 
S afet y A n al ysis 
D escri pti v e statistics will b e c o m p ute d f or safet y p ara m eters, as a p pr o priate.  
N u m b er a n d p erce nta g e of s u bjects w h o disc o nti n u e d fr o m t h e st u d y b eca use of 
A Es will b e ta b ulate d acr oss d ose c o h orts; se v erit y a n d fre q u e n c y of A Es a n d 
seri o us a d v ers e e v e nts ( S A Es) will als o b e ta b ulate d acr oss tre at me nt gr o u ps.  
All ot h er safet y d ata will b e pr o vi d e d i n listi n gs.  P h ysical e x a mi n ati o n 
fi n di n gs, cli nical la b orat or y v al u es, a n d vital si g ns will b e s u m m arize d b y d ose 
c o h ort. 
T h e pr o p orti o n of s u bjects wit h m eas ura bl e a nti b o dies t o G E M 1 0 3 will b e 
dis pla y e d. 
F urt h er statisti cal e v al u ati o ns will b e a p plie d f or select e n d p oi nts, if w arra nte d.  
All b aseli n e d at a a n d safet y d ata c oll ecte d d uri n g t h e st u d y will b e liste d f or 
eac h s u bject. 
All A Es will b e c o d e d usi n g a c o nsiste nt v ersi o n of t h e Me dical Dicti o n ar y f or 
Re g ulat or y Acti vities ( Me d D R A, versi o n 2 2. 0 or hi g h er) a n d will be classifie d 
b y Me d D R A s yste m or g a n class ( S O C) a n d preferre d ter m ( P T). 
A E a n al yses will i n cl u d e t h e f oll o wi n g ta b ular s u m maries: 
•
 S u m mar y
 
of
 
all
 A Es
 
•  
I n ci d e n ce of A Es b y S O C a n d P T 
•  
I n ci d e n ce of A Es b y se v erit y 
•  
I n ci d e n ce of S A Es 
•  
I n ci d e n ce of treat me nt-r elate d A Es 
Bi o m a r ker, I m a gi n g, a n d Cli nic al E n d p oi nt A n al ysis 
A q u e o us h u m or will b e c ollect e d pri or t o t h e first d ose, a n d j ust pri or t o eac h 
s u bse q u e nt I V T i njecti o n of G E M 1 0 3 t o e v al uate c o m ple m e nt pr otei ns a n d 
p ossi bl y i nfla m mat or y c yt o ki n e pr ofiles t o d eter mi n e t h eir p ote ntial as P D 
bi o mar k ers f or usef ul n ess i n a pi v otal st u d y.  T otal C F H c o nce ntrati o ns i n 
a q u e o us h u m or will b e e v al u ate d. 

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5 Ma y 2 0 2 1 
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G E MI NI T H E R A P E U TI C S I N C P R O P RI E T A R Y A N D C O N FI D E N TI A L:  
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S I N C. 
I ma gi n g e n d p oi nts s u c h as C N V lesi o n size, M A lesi o n size, reti n al la y er 
t hic k ness or prese n ce of fl ui d, a n d cli nical e n d p oi nts s u c h as B C V A, L L V A, 
a n d l o w l u mi n a n ce d eficit, will b e c ollecte d as d escri b e d i n t h e sc h e d ule of 
ass ess m e nts. 
A n al yses of bi o mar k ers, i ma gi n g assess m e nts, a n d cli nical e n d p oi nts will b e 
d escri pti v e, a n d will s u m mariz e act u al v al u es a n d c h a n g es fr o m b aseli n e o v er 
ti me.  Gra p hic al dis pla ys will als o b e create d. 
A n al ysis of bi o m ar k er, i ma gi n g, a n d cli nical e n d p oi nt c h a n g es fr o m b aseli n e 
will pri maril y e m pl o y t h e Wilc o x o n ra n k-s u m test. 
F ull a n al ysis d etails will b e pr o vi d e d i n t h e Statistic al A n al ysis Pla n. 
 

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5 Ma y 2 0 2 1 
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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
1  I N T R O D U C TI O N 
T his st u d y will be c o n d ucte d acc or di n g t o G o o d Cli nical Practice ( G C P), as defi ne d b y t he 
I nter nati o nal C o u ncil f or Har m o nisati o n (I C H) a n d t he et hical pri nci ples u n derl yi n g E ur o pea n 
U ni o n ( E U) Directi ves 2 0 0 1/ 2 0/ E C  a n d E U Directi ves 2 0 0 5/ 2 8/ E C ; t he U nite d States ( U S) C o de 
of Fe deral Re g ulati o ns ( C F R), Title 2 1, Parts 5 0 a n d 3 1 2 ( 2 1 C F R 5 0, 2 1 C F R 3 1 2) ; a n d all 
a p plica ble g o ver n me nt re g ulati o ns a n d i nstit uti o nal researc h p olicies a n d pr oce d ures. 
1. 1  B ac k gr o u n d 
1. 1. 1  Dise ase 
A ge-relate d mac ular de ge nerati o n ( A M D) is a c o n diti o n affecti n g ol der pe o ple t hat i n v ol ves t he 
pr o gressi ve l oss of t he ce ntral fiel d of visi o n a n d it is t he lea di n g ca use of irre versi ble bli n d ness 
i n t he wester n w orl d (W orl d Healt h Or ga nizati o n [ W H O] 2 0 1 9 ).  T w o f or ms of a d va nce d A M D 
ca n be disti n g uis he d: ne o vasc ular ( wet) A M D ( n A M D) a n d dr y A M D.  Ne o vasc ular A M D is 
visi o n l oss i n t he wester n w orl d i n i n di vi d uals 5 5 years or ol der.  Alt h o u g h n A M D acc o u nts f or 
wit h t he disease ( K ha na ni 2 0 2 0, H ole ka m p 2 0 1 9 ).  T he c urre nt sta n dar d of care ( S o C) f or 
n A M D is t he i ntra vitreal deli ver y of f u ncti o nal a nta g o nists of vasc ular e n d ot helial gr o wt h fact or 
( V E G F), a pr otei n i n v ol ve d i n t he m olec ular orc hestrati o n of t he pat h ol o gic ne o vasc ular casca de 
(Sa h ni 2 0 2 0 , Jaffe 2 0 1 6).  H o we ver, t here are se veral practical li mitati o ns t o a nti- V E G F t hera p y, 
i ncl u di n g t he nee d f or fre q ue nt i ntra vitreal i njecti o ns, i nc o m plete res p o nse, a n d/ or fail ure t o 
mai ntai n res p o nse i n s o me patie nts ( Jaffe 2 0 1 6).  A d diti o nall y, t here is s o me c o ncer n t hat l o n g-
ter m use of a nti- V E G F a ge nts ma y ha ve a n u n desira ble effect o n t he mac ula, p ossi bl y relate d t o 
t he r ole t hat V E G F pla ys i n mai ntai ni n g t he i nte grit y of t he reti nal pi g me nt e pit heli u m 
(Gillies 2 0 2 0 ).  De vel o p me nt of mac ular atr o p h y ( M A) i n e yes wit h ne o vasc ular A M D treate d 
wit h a ge nts tar geti n g V E G F has als o bee n re p orte d i n se veral st u dies ( Sa d da 2 0 1 8 , Gillies 2 0 2 0 ). 
Ne o vasc ular A M D is c haracterize d b y t he u nc o ntr olle d pr oliferati o n of a b n or mal mac ular bl o o d 
vessels t hat ca n lea k fl ui d a n d bl o o d, res ulti n g i n da ma ge t o t he p h ot orece pt ors a n d t he  reti nal 
pi g me nt e pit heli u m ( R P E), a pr ocess k n o w n as c h or oi dal ne o vasc ularizati o n ( C N V) 
(H ole ka m p 2 0 1 9 ).  V E G F, t he pri nci pal dri ver of ne o vasc ularizati o n i n A M D, i n d uces 
a n gi o ge nesis a n d i ncreases vasc ular per mea bilit y a n d i nfla m mati o n.  O ver ti me, t his ca uses 
pr o gressi ve de ge nerati o n of p h ot orece pt ors a n d t he R P E, a n d reti nal fl ui d ca n acc u m ulate, 
lea di n g t o e de ma a n d f u ncti o nal deteri orati o n (H ole ka m p 2 0 1 9, K ha na ni 2 0 2 0 ).  D ysre g ulati o n 
of R P E- deri ve d V E G F is ass ociate d wit h ne o vasc ularizati o n i n n A M D.  Si nce ge netic varia nts i n  
c o m ple me nt fact or H ( C F H) are k n o w n ris k fact ors f or A M D; i n a meta nal ysis, C F H 
p ol y m or p his m rs 1 0 6 1 1 7 0 was a pre dict or of treat me nt res p o nse of ne o vasc ular A M D, es peciall y 
f or a nti- V E G F a ge nts ra ni biz u ma b a n d be vaciz u ma b (C he n 2 0 1 2 ).  I n di vi d uals h o m oz y g o us f or 
t he varia nt ris k C-allele c orres p o n de d t o a decrease d res p o nse t o treat me nt b y a p pr o xi matel y 
1. 6-f ol d w he n c o m pare d wit h patie nts carr yi n g h o m oz y g o us f or T-allele ( C he n 2 0 1 2 ).  Dr use n 
de p osits ass ociate d wit h ge netic varia nts of i nterest t o t he S p o ns or ha ve als o bee n s h o w n t o 
i ncrease t he ris k of pr o gressi o n fr o m earl y or i nter me diate A M D t o a d va nce d A M D ( ge o gra p hic 
atr o p h y [ G A] a n d n A M D) ( C ha vali 2 0 1 5 , Merle 2 0 2 0).  I n b ot h dr y a n d n A M D patie nts, oc ular 
c o m ple me nt acti vati o n has bee n re p orte d wit h c o m ple me nt de p osits detecte d i n dr use n, o n R P E 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
cells, Br uc h’s me m bra ne, c h ori oca pillaris, a n d c o m ple me nt acti vati o n pr o d ucts ha ve als o bee n 
s h o w n i n a q ue o us h u m or (Keir 2 0 1 7 , Sc hic k 2 0 1 7 , Alta y 2 0 1 9 ). 
E n d o ge n o us (i ntra oc ular) C F H is cr ucial i n re g ulati n g t he alter nati ve pat h wa y ( A P) of 
c o m ple me nt a m plificati o n l o o p.  I ntra oc ular h u ma n rec o m bi na nt C F H has als o bee n s h o w n t o 
re d uce C N V as efficie ntl y as c urre ntl y use d a nti- V E G F a nti b o d y i n a m o use m o del f or n A M D 
(B orras 2 0 2 0 ).  F u ncti o nal C F H als o has r oles i n A M D t hat are necessar y t o mai ntai n 
h o me ostasis i n t he s u breti nal s pace, i ncl u di n g assista nce i n R P E cleara nce of pr o d ucts of li pi d 
o xi dati o n a n d cell ular de bris t hat are necessar y t o mai ntai n h o me ostasis i n t he s u breti nal s pace, 
a n d w hic h are n o n-ca n o nical a n d se parate fr o m t he c o m ple me nt re g ulati o n pr o vi de d b y 
f u ncti o nal C F H (Cali p pe 2 0 1 7 , Matta pallil 2 0 1 7,  La n d o ws ki 2 0 1 9 , Y u 2 0 2 0 ).  T heref ore, 
pr o vi di n g s u pra p h ysi ol o gical r h C F H ( G E M 1 0 3) as a n A P c o m ple me nt m o d ulat or y t hera p y has 
p ote ntial t o be a n effecti ve treat me nt f or n A M D t o a de q uatel y a d dress h y peracti ve c o m ple me nt 
acti vati o n, R P E f u ncti o nal deficits, a n d res ulta nt reti nal atr o p h y ca use d b y C F H i ns ufficie nc y 
(Keir 2 0 1 7 , B orras 2 0 2 0 ).  Ta ke n t o get her, t hese res ults clearl y i de ntif y n o vel mec ha nis ms of 
C F H i n t he n A M D pr ocess a n d de m o nstrate t he p ote ntial of G E M 1 0 3 as a n o vel, t hera pe utic 
o pti o n f or patie nts wit h n A M D. 
1. 1. 2  Me dic al R ati o n ale f or G E M 1 0 3 
Ge mi ni T hera pe utics, I nc. (t he S p o ns or) is de vel o pi n g G E M 1 0 3 (rec o m bi na nt h u ma n 
c o m ple me nt fact or H [r h C F H]) as a n A P c o m ple me nt m o d ulat or y t hera p y f or t he treat me nt of 
n A M D.  G E M 1 0 3 is a gl yc o pr otei n of a p pr o xi matel y 1 5 5 kil o dalt o ns ( k Da) ma de u p of 2 0 of t he 
C F H c o ntr ol pr otei n m o d ules j oi ne d b y s h ort li n kers ( 3 t o 8 a mi n o aci ds i n le n gt h).  T he c urre nt 
S o C f or n A M D is t he i ntra vitreal deli ver y of f u ncti o nal a nta g o nists of V E G F, a pr otei n i n v ol ve d 
i n t he m olec ular orc hestrati o n of t he pat h ol o gic ne o vasc ular casca de (Sa h ni 2 0 2 0 , Jaffe 2 0 1 6).  
H o we ver, si g nifica nt u n met nee d e xists wit h a nti- V E G F m o n ot hera p y ( Jaffe 2 0 1 6).  T h us, n o vel, 
alter nati ve, a n d m ulti-tar get t hera pies t hat pr o vi de rest orati o n of reti nal healt h, i m pr o ve d efficac y 
a n d e xte n de d d ura bilit y o ver a nti- V E G F t hera p y are nee de d f or patie nts wit h n A M D 
(Sa h ni 2 0 2 0 , B orras 2 0 2 0 ). 
F u ncti o nal C F H is critical f or re g ulati n g t he A P a m plificati o n l o o p as well as C 3 c o n vertase 
acti vit y (Br o dsz ki 2 0 2 0 , Trie b wasser 2 0 1 5 , Geerli n gs 2 0 1 7 ).  Rest ori n g reti nal healt h b y 
pr o vi di n g f u ncti o nal C F H has a p ote ntial f or be nefit t o patie nts wit h n A M D.  C F H has a n a bilit y 
t o a d dress R P E f u ncti o nal deficits a n d res ulta nt reti nal atr o p h y ca use d b y C F H i ns ufficie nc y 
(Keir 2 0 1 7 , B orras 2 0 2 0 ).  A d diti o nall y, i n a m uri ne m o del of n A M D, i ntra oc ular h u ma n 
rec o m bi na nt C F H has bee n s h o w n t o re d uce C N V as efficie ntl y as c urre ntl y use d a nti- V E G F 
a nti b o d y ( B orras 2 0 2 0 ).  G E M 1 0 3 is i nte n de d t o b ot h rest ore a p pr o priate re g ulati o n of t he 
c o m ple me nt s yste m a n d t o hel p mai ntai n reti nal healt h.  I n vitr o a nal yses s u p p ort t he h y p ot hesis 
t hat G E M 1 0 3 rest ores a p pr o priate re g ulati o n b y bl oc ki n g t he detri me ntal effects (e. g., 
i na p pr o priate cell l ysis, i m m u ne res p o nse) w hile retai ni n g t he be neficial effects (e. g., cleara nce 
of e xtracell ular de bris, re pair of o xi dati ve da ma ge) of p h ysi ol o gic c o m ple me nt acti vit y.  
F u ncti o nal C F H als o has r oles i n t he oc ular c o m part me nt, i ncl u di n g assista nce i n R P E cleara nce 
of pr o d ucts of li pi d o xi dati o n a n d cell ular de bris t hat are necessa r y t o mai ntai n h o me ostasis i n 
t he s u breti nal s pace, a n d w hic h are n o n-ca n o nical a n d se parate fr o m t he c o m ple me nt re g ulati o n 
pr o vi de d b y f u ncti o nal C F H ( Cali p pe 2 0 1 7 , Matta pallil 2 0 1 7 , Y u 2 0 2 0 ).  G E M 1 0 3 is i nte n de d t o 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 2 2 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
be use d as a n A P c o m ple me nt m o d ulat or y t hera p y f or t he treat me nt of n A M D b y pr o vi di n g 
s u pra p h ysi ol o gical r h C F H b y i ntra vitreal (I V T) i njecti o n. 
G E M 1 0 3 has bee n teste d i n a variet y of bi oc he mical assa ys a n d n o ncli nical st u dies ( Secti o n 1. 3 ) 
a n d ha d a p pr o priate acti vit y, oc ular e x p os ure, a n d safet y pr ofile t o s u p p ort cli nical testi n g of 
G E M 1 0 3 i n n A M D patie nts.  I n a d diti o n, G E M 1 0 3 was e val uate d i n a n o n g oi n g P hase 1 si n gle 
asce n di n g d ose st u d y ( G E M- C L- 1 0 3 0 1) a n d is bei n g e val uate d i n a n o n g oi n g P hase 2a m ulti ple-
d ose st u d y ( G E M- C L- 1 0 3 0 2) i n patie nts wit h dr y A M D.  A vaila ble preli mi nar y cli nical data as 
of 3 0 Se pte m ber 2 0 2 0 fr o m t he o n g oi n g st u dies i n patie nts wit h dr y A M D, pri maril y after si n gle 
d oses of G E M 1 0 3, i n dicate t hat G E M 1 0 3 is well-t olerate d, ac hie ves s u pra p h ysi ol o gical le vels of 
G E M 1 0 3 i n a q ue o us h u m or, s h o ws a tre n d f or p ositi ve effects o n e x pl orat or y bi o mar kers of 
c o m ple me nt acti vati o n, a n d s h o ws a tre n d f or mai ntai ne d or i m pr o ve d vis ual ac uit y ( V A) 
(Secti o n 1. 4 ).  T hese data s u p p ort t he pla n ne d cli nical e val uati o n of G E M 1 0 3 i n n A M D patie nts 
i n t his P hase 2a cli nical st u d y. 
1. 2  I n vesti g ati o n al Me dici n al Pr o d uct ( G E M 1 0 3) 
G E M 1 0 3, r h C F H, is a gl yc o pr otei n of a p pr o xi matel y 1 5 5 kil o dalt o ns ma de u p of 2 0 of t he C F H 
c o ntr ol pr otei n m o d ules j oi ne d b y s h ort li n kers ( 3 t o 8 a mi n o aci ds i n le n gt h).  G E M 1 0 3 is 
f or m ulate d i n 0
v ol u me p ol ys or bate 2 0, p H 7. 0 f or a d mi nistrati o n via I V T i njecti o n, pr o vi di n g direct access i nt o 
t he tar get or ga n ( or) tiss ue.  T he G E M 1 0 3 dr u g pr o d uct will be ma n ufact ure d as a f or m ul ate d, 
b uffere d s ol uti o n at 1 0 m g/ m L r h C F H c o nce ntrate d li q ui d t hat, ca n be dil ute d (as nee de d) t o t he 
a p pr o priate c o nce ntrati o n pri or t o d osi n g at t he site. 
1. 3  N o ncli nic al S u m m ar y 
T he p har mac ol o g y, p har mac o ki netics ( P K), a n d t o xic ol o g y of G E M 1 0 3 were e val uate d i n a 
series of i n vitr o a n d i n vi v o n o ncli nical st u dies. 
T he bi ol o gical acti vit y of G E M 1 0 3 was f o u n d t o be c o m para ble t o e n d o ge n o us h u ma n 
plas ma- p urifie d C F H, a n d c o nsiste nt wit h literat ure-re p orte d val ues of C F H i n t he sa me i n vitr o 
m o dels.  T hese data de m o nstrate t hat G E M 1 0 3 e xerts t he desire d bi ol o gical effect, a n d t he 
p ote nc y of G E M 1 0 3 is c o m para ble a n d e q ui vale nt t o t hat of e n d o ge n o us h u ma n C F H.  I n 
a d diti o n, G E M 1 0 3 e x vi v o acti vit y e val uate d b y t he c o m ple me nt fact or I c ofact or assa y o n 
vitre o us sa m ples o btai ne d fr o m G E M 1 0 3-treate d c y n o m ol g us m o n ke ys s h o we d t hat acti vit y was 
mai ntai ne d fr o m 1 4 t o 2 7 da ys after a si n gle I V T a d mi nistrati o n of G E M 1 0 3 at d oses ra n gi n g 
fr o m 1 5 0 μ g/e ye t o 1 0 0 0 μ g/e ye.  Literat ure s u p p orts t he a bilit y of C F H t o a d dress t he R P E 
f u ncti o nal deficits a n d res ulta nt reti nal atr o p h y ca use d b y C F H i ns ufficie nc y (Keir 2 0 1 7 , 
B orras 2 0 2 0, Di n g 2 0 1 5 ).  A d diti o nall y, i n a m uri ne m o del of n A M D, i ntra oc ular h u ma n 
rec o m bi na nt C F H has bee n s h o w n t o re d uce C N V as efficie ntl y as c urre ntl y use d a nti- V E G F 
a nti b o d y ( B orras 2 0 2 0 ). 
se q ue nce h o m ol o g y bet wee n h u ma ns a n d c y n o m ol g us m o n ke ys c o m pare d wit h ot her s pecies’ 
pr otecte d c y n o m ol g us m o n ke y er yt hr oc ytes fr o m he m ol ysis i n C F H- de plete d h u ma n ser u m b ut 
di d n ot pr otect ra b bit er yt hr oc ytes i n t he sa me assa y.  T he res ults of t hese st u dies de m o nstrate d 
t hat n o n h u ma n pri mates are t he m ost rele va nt s pecies f or t he n o ncli nical safet y assess me nt of 
G E M 1 0 3. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 2 3 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
Safet y p har mac ol o g y assess me nts of ce ntral ner v o us, res pirat or y, a n d car di o vasc ular s yste ms 
after si n gle a n d 3- m o nt h o nce m o nt hl y re peate d d oses of I V T a d mi nistrati o n i n c y n o m ol g us 
m o n ke ys s h o we d n o G E M 1 0 3-relate d effects o n t he f u ncti o n of t hese or ga n s yste ms at 5 0, 1 0 0, 
or 2 5 0 μ g/e ye. 
T he P K, t o xic o ki netic, a n d distri b uti o n pr o perties of G E M 1 0 3 were e val uate d base d o n t he 
ser u m, vitre o us h u m or, a q ue o us h u m or, reti na, R P E, a n d c h or oi d after si n gle or re peate d I V T 
a d mi nistrati o n t o c y n o m ol g us m o n ke ys.  After I V T i njecti o n, t he vitre o us h u m or, a q ue o us 
h u m or, reti na, R P E, a n d c h or oi d c o nce ntrati o n of G E M 1 0 3 were s ustai ne d i n c y n o m ol g us 
m o n ke ys, s u p p orti n g t he i nte n de d I V T r o ute of a d mi nistrati o n i n h u ma ns.  G E M 1 0 3 e x p os ure 
i ncrease d wit h i ncrease i n d ose i n a n a p pr o xi matel y pr o p orti o nal ma n ner after I V T i njecti o n.  
G E M 1 0 3 ra pi dl y distri b ute d t o a q ue o us h u m or, reti na, R P E, a n d c h or oi d wit h eli mi nati o n half-
life ra n gi n g fr o m 2. 9 8 t o 4. 4 3 da ys i n vitre o us h u m or, fr o m 2. 8 6 t o 4. 2 7 da ys i n a q ue o us h u m or, 
fr o m 2. 5 3 t o 6. 8 3 da ys i n reti na, fr o m 6. 2 7 t o 8. 2 7 da ys i n R P E, a n d fr o m 6. 1 2 t o 9. 5 0 da ys i n 
c h or oi d.  G E M 1 0 3 was f o u n d t o be relati vel y sta ble i n t he d ose site ( vitre o us h u m or) a n d at t he 
tar get tiss ue ( R P E).  G E M 1 0 3 efficie ntl y distri b ute d i nt o t he a q ue o us h u m or, reti na, R P E, a n d 
c h or oi d wit h ma xi m u m c o nce ntrati o n ( C ma x
t hat of vitre o us h u m or Cma x , res pecti vel y, a n d wit h area u n der c ur ve ( A U C) val ues of 
distri b uti o n at stea d y-state is a p pr o xi matel y 1-f ol d t o 5. 9-f ol d greater t ha n c y n o m ol g us m o n ke y 
vitre o us v ol u me, a n d is a p pr o xi matel y 0. 7-f ol d t o 3. 9-f ol d greater t ha n c y n o m ol g us m o n ke y 
w h ole e ye v ol u me t hat s u g gest t hat G E M 1 0 3 is mai nl y c o ntai ne d t o t he e ye.  T he t otal cleara nce 
of G E M 1 0 3 is a p pr o xi matel y t he rate of drai na ge of a q ue o us h u m or fr o m t he u ve o-scleral r o utes 
b y t he a nteri or c ha m ber or b y c o n ve nti o nal r o utes. 
T he s yste mic e x p os ure of G E M 1 0 3 after a si n gle i njecti o n was mi ni mal at a p pr o xi matel y 
After re peate d ( o nce m o nt hl y) d oses f or a t otal of 3 d oses at 5 0, 
1 0 0, or 2 5 0 μ g/e ye, s yste mic G E M 1 0 3 e x p os ure was mi ni mal a n d o bser ve d i n t he 1 0 0 a n d 
2 5 0 μ g/e ye d ose gr o u ps after t he first d ose b ut n ot after t he sec o n d or t hir d d ose.  T his ma y be a 
res ult of t he m o derate t o se vere i nfla m mati o n o bser ve d i n t he a ni mals after t he first d ose d ue t o 
ge nerati o n of G E M 1 0 3 a nti dr u g a nti b o dies ( A D A), as A D A detecti o n ge nerall y c orres p o n de d 
wit h t o xic o ki netic sa m ples t hat were bel o w t he li mit of q ua ntificati o n. 
T he t o xicit y pr ofile of G E M 1 0 3 has bee n well-c haracterize d i n si n gle- d ose ra n ge-fi n di n g st u dies, 
G o o d La b orat or y Practice ( G L P)-c o m plia nt, e x pa n de d, ac ute, si n gle- d ose, 3- m o nt h a n d 6- m o nt h 
re peate d- d ose ( o nce m o nt hl y) t o xic ol o g y st u dies, as well as si n gle- d ose a n d 3- m o nt h re peate d 
d ose ( o nce m o nt hl y) safet y p har mac ol o g y st u dies i n c y n o m ol g us m o n ke ys.  T here were n o 
G E M 1 0 3-relate d s yste mic t o xicities i n cli nical pat h ol o g y or s yste mic hist o pat h ol o g y effects 
o bser ve d.  G E M 1 0 3-attri b uta ble oc ular fi n di n gs i n t he t o xic ol o g y st u dies were c o nsiste nt acr oss 
st u dies a n d li mite d t o oc ular i nfla m mat or y reacti o ns t hat were li kel y i m m u ne-relate d res p o nses 
res ulti n g fr o m t he ge nerati o n of G E M 1 0 3 A D A after t he a d mi nistrati o n of a rec o m bi na nt h u ma n 
pr otei n t o c y n o m ol g us m o n ke ys ( S h ort 2 0 0 8 , Bi ol o gics Lice nse A p plicati o n [ B L A] 1 2 5 1 5 6 , 
B L A 1 2 5 3 8 7 ).  G E M 1 0 3 A D As were m ostl y o bser ve d starti n g o n Da y 1 5 i n all G E M 1 0 3-treate d 
a ni mals acr oss st u dies a n d teste d d oses.  T o xic ol o g y st u dies i n dicate d t hat fi n di n gs of 
i nfla m mati o n i n t he e ye c oi nci de d wit h t he ti me of A D A ge nerati o n i n m ost a ni mals. 
A n o- o bser va ble-a d verse-effect le vel c o ul d n ot be deter mi ne d f or eit her t he si n gle- d ose, 3- m o nt h 
or 6- m o nt h re peat- d ose ( o nce m o nt hl y) st u dies beca use of a nti b o d y pr o d ucti o n a gai nst a h u ma n 
pr otei n.  T hese G L P-c o m plia nt st u dies i n dicate d t hat G E M 1 0 3 was t olera ble u p t o t he hi g h d ose 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 2 4 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
of 2 5 0 μ g/e ye, wit h o nl y oc ular i nfla m mat or y fi n di n gs d ue t o a n i m m u n o ge nic res p o nse of 
G E M 1 0 3 A D A ge nerati o n as a ntici pate d f or a n I V T-a d mi nistere d h u ma n pr otei n ( S h ort 2 0 0 8 ). 
F urt her details o n t he n o ncli nical p har mac ol o g y, P K, a n d t o xic ol o g y of G E M 1 0 3 ma y be f o u n d 
i n t he I n vesti gat or’s Br oc h ure. 
1. 4  Cli nic al S u m m ar y 
As of 2 3 Se pte m ber 2 0 2 0, 1 2 dr y A M D s u bjects ( 3 per d ose) wit h bilateral G A ha d recei ve d a 
si n gle d ose of G E M 1 0 3 i n t he P hase 1 si n gle asce n di n g d ose cli nical st u d y ( G E M- C L- 1 0 3 0 1) at 
5 0, 1 0 0, 2 5 0 a n d 5 0 0 
-li miti n g t o xicities a n d n o relate d a d verse e ve nts ( A Es) 
were re p orte d.  Base d o n a vaila ble preli mi nar y data, t here were n o si g ns of i ntra oc ular 
i nfla m mati o n a n d n o cli nicall y rele va nt c ha n ges i n best c orrecte d vis ual ac uit y ( B C V A), 
i ntra oc ular press ure (I O P), e n d o ge n o us plas ma C F H le vels, or safet y la b orat or y res ults.  I n 
a d diti o n, t he preli mi nar y res ults e val uati n g t he ge nerati o n of a nti b o dies a gai nst G E M 1 0 3 i n 
ser u m of patie nts recei vi n g 5 0 μ g/e ye t o 5 0 0 μ g/e ye at all assesse d ti me p oi nts were ne gati ve. 
G E M 1 0 3 mea n c o nce ntrati o n i n a q ue o us h u m or was mai ntai ne d at or a b o ve 6 8. 3 n g/ m L ( mea n 
e n d o ge n o us le vel of C F H i n n or mal s u bjects) f or a d urati o n of at least 2 8 da ys after I V T 
i njecti o n at all d oses teste d, i n dicati n g ac hie ve me nt of s u pra p h ysi ol o gical le vels of G E M 1 0 3. 
A vaila ble preli mi nar y mea n p har mac o d y na mic ( P D) data s h o we d a tre n d f or p ositi ve effects o n 
e x pl orat or y mar kers of c o m ple me nt acti vati o n ( C 3a a n d Ba), at all d oses. 
As of 3 0 Se pte m ber 2 0 2 0, 1 0 dr y A M D s u bjects ha ve als o recei ve d a si n gle d ose of G E M 1 0 3 i n 
t he P hase 2a m ulti ple- d ose) cli nical st u d y ( G E M- C L- 1 0 3 0 2); t he first dr y A M D s u bject i n t his 
st u d y has recei ve d 2 d oses of G E M 1 0 3.  N o seri o us a d verse e ve nts ( S A Es) were re p orte d.  
Ser u m A D A f or t he 1 s u bject w h o recei ve d 2 d oses a n d w h o ha d p ost- d ose sa m pli n g after t heir 
first d ose as per pr ot oc ol was ne gati ve at Da y 3 0; t he ne xt sa m pli n g ti me p oi nt f or ser u m A D A 
per pr ot oc ol is after t he f o urt h d ose.  Base d o n a vaila ble preli mi nar y P K data fr o m t he first 
s u bject t hat recei ve d 2 d oses as of 3 0 Se pte m ber 2 0 2 0, s u pra p h ysi ol o gical le vels of C F H were 
mai ntai ne d.  N o P D data were a vaila ble fr o m t his st u d y as 3 0 Se pte m ber 2 0 2 0. 
Details o n t he cli nical pr ofile of G E M 1 0 3 are pr o vi de d i n t he I n vesti gat or’s Br oc h ure. 
1. 5  D ose R ati o n ale a n d Ris k/ Be nefits 
1. 5. 1  St u d y D ose R ati o n ale 
T his P hase 2a st u d y ( G E M- C L- 1 0 3 1 1) will e val uate t he safet y, t olera bilit y, i m m u n o ge nicit y, 
P K/ P D, c o m ple me nt bi o mar kers, a n d cli nical efficac y of re peat I V T i njecti o ns of 
G E M 1 0 3 +sta n dar d of care ( S o C) defi ne d as afli berce pt e ver y ot her m o nt h [ E O M]; c o m pare d 
wit h s ha m + S o C) i n s u bjects wit h n A M D. 
Data fr o m eac h d ose i n t he P hase 1 si n gle asce n di n g d ose st u d y ( G E M- C L- 1 0 3 0 1) i n dr y A M D 
patie nts has bee n e val uate d f or safet y, G E M 1 0 3 e x p os ure, a n d bi o mar ker res p o nse, a n d has bee n 
use d t o i nf or m t he selecti o n of t he 5 0 0 μ g/e ye d ose f or e val uati o n i n t his P hase 2a m ulti ple- d ose 
st u d y i n s u bjects wit h n A M D. 
Re peat d oses of G E M 1 0 3 will be a d mi nistere d b y I V T i njecti o n t o s u bjects wit h n A M D.  T he 
5 0 0 μ g/e ye was base d o n safet y data fr o m si n gle- a n d re peat- d ose ( u p t o 3 a n d u p t o 6 o nce 
m o nt hl y) I V T t o xic ol o g y st u dies i n c y n o m ol g us m o n ke ys, P K m o deli n g a n d si m ulati o n of t he 
pr ofiles of G E M 1 0 3 after a si n gle I V T i njecti o n i n c y n o m ol g us m o n ke ys, a n d t he e n d o ge n o us 
le vel of C F H i n h u ma n R P E (t he tar get oc ular tiss ue of G E M 1 0 3 re place me nt t hera p y i n dr y 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 2 5 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A M D patie nts), as well as data fr o m t he P hase 1 si n gle asce n di n g d ose st u d y ( G E M- C L- 1 0 3 0 1) 
as descri be d i n Secti o n 1. 4 .  T he 5 0 0 μ g/e ye d ose le vel (i n G E M- C L- 1 0 3 0 2 pr ot oc ol versi o n 2. 0) 
was base d o n t he cli nical e x perie nce wit h 5 0, 1 0 0, 2 5 0, a n d 5 0 0 μ g i n t he P hase 1 si n gle 
asce n di n g d ose st u d y ( G E M- C L- 1 0 3 0 1). 
N o ncli nical G L P-c o m plia nt, si n gle- a n d re peat- d ose ( o nce m o nt hl y) I V T st u dies i n dicate d t hat 
G E M 1 0 3 was t olera ble u p t o t he hi g h d ose of 2 5 0 μ g/e ye, wit h o nl y oc ular i nfla m mat or y 
fi n di n gs d ue t o a n i m m u n o ge nic res p o nse of G E M 1 0 3- A D A ge nerati o n as a ntici pate d f or a n 
I V T-a d mi nistere d h u ma n pr otei n (S h ort 2 0 0 8 ).  T he h u ma n e q ui vale nt d ose f or t he hi g hest teste d 
t olera ble d ose ( 2 5 0 μ g/e ye) i n c y n o m ol g us m o n ke ys (f or t he e x pa n de d ac ute si n gle- d ose a n d 
3- m o nt h re peat- d ose [ o nce m o nt hl y f or a t otal of 3 d oses] a n d 6- m o nt h re peat d ose [ o nce 
m o nt hl y f or a t otal of 6 d oses] t o xicit y st u dies) is 5 0 0 μ g/e ye, calc ulate d base d o n a 2-f ol d lar ger 
h u ma n vitre o us v ol u me ( h u ma n vitre o us v ol u me is a p pr o xi matel y 4 m L, w hereas c y n o m ol g us 
m o n ke y vitre o us v ol u me is a p pr o xi matel y 2 m L).  A brief s u m mar y of a vaila ble cli nical safet y 
data is pr o vi de d i n Secti o n 1. 4 . 
D ose selecti o n was base d o n b ot h t he P K m o deli n g a n d si m ulati o n of t he pr ofiles of G E M 1 0 3 
after a si n gle I V T i njecti o n i n c y n o m ol g us m o n ke y, a n d t he e n d o ge n o us le vel of C F H i n h u ma n 
R P E, t he tar get oc ular tiss ue of G E M 1 0 3 re place me nt t hera p y i n A M D.  T he a vera ge 
e n d o ge n o us le vel of C F H i n R P E is olate d fr o m fr oze n ca da ver h u ma n e yes is 1 5 7 7 n g/ g (ra n ge 
fr o m 4 8 8. 0 6 t o 3 4 6 9. 7 n g/ g).  T his was ass u me d t o be t he n or mal e n d o ge n o us le vel f or t he 
p ur p ose of pr ojecti o n of effecti ve G E M 1 0 3 c o nce ntrati o ns a n d d urati o n of effect p ost I V T 
a d mi nistrati o n.  C F H ha pl oi ns ufficie nc y has bee n i de ntifie d as a ris k fact or f or dr y A M D, w hic h 
(Trie b wasser 2 0 1 5 , Geerli n gs 2 0 1 7 ).  T heref ore, f or C F H re place me nt t hera p y i n A M D patie nts, 
 n g/ g) of t he n or mal e n d o ge n o us c o nce ntrati o ns of 
C F H i n R P E is c o nsi dere d t o be s ufficie nt f or cli nical effect.  Base d o n t his ass u m pti o n, P K 
m o deli n g a n d si m ulati o n were c o n d ucte d usi n g c y n o m ol g us m o n ke y P K para meters t o pr oject 
 n g/ g after a si n gle I V T a d mi nistrati o n i n 
h u ma ns at d oses ra n gi n g fr o m 5 0 t o 7 5 0 μ g/e ye.  T he P K m o del ass u me d t hat t he half-life of 
G E M 1 0 3 i n h u ma n R P E is 2- t o 3-f ol d l o n ger t ha n i n c y n o m ol g us m o n ke y R P E, a n d t hat t he 
vitre o us v ol u me i n h u ma n is 2-f ol d greater t ha n i n c y n o m ol g us m o n ke y ( Ga u drea ult 2 0 0 5 , 
Kr o h ne 2 0 1 2 , X u 2 0 1 3 ).  G E M 1 0 3 R P E c o nce ntrati o ns are e x pecte d t o be > 8 0 0 n g/ g f or 8 7 t o 
1 3 2 da ys after a si n gle I V T d ose of 5 0 0 μ g/e ye i n h u ma ns.  O verall, t he data i n dicate t hat t he 
n o ncli nical oc ular P K, distri b uti o n, a n d s yste mic P K c haracteristics of G E M 1 0 3 s u p p ort t he 
i nte n de d cli nical r o ute of a d mi nistrati o n (I V T i njecti o n), d ose, a n d re gi me n ( o nce m o nt hl y, or 
less fre q ue ntl y) f or t he treat me nt of A M D. 
1. 5. 2  Ris k/ Be nefit Assess me nt f or St u d y Dr u g a n d St u d y Pr oce d ures 
P ote nti al Ris ks of G E M 1 0 3:  I m m u n o ge nicity a n d I nfl a m m ati o n 
T he pre d o mi na nt o p ht hal mic a n d hist o pat h ol o gic fi n di n gs i n c y n o m ol g us m o n ke ys were 
se q uelae ass ociate d wit h, a n d sec o n dar y t o, a n i m m u n o ge nic res p o nse, c o nsiste nt wit h a n 
e x pecte d i m m u n o ge nic res p o nse t o a h u ma n pr otei n.  N o de ge nerati ve or a p o pt otic disr u pti o ns 
were n ote d.  T hese i m m u n o ge nic res p o nses are less li kel y t o be ge nerate d i n t he cli nic si nce 
G E M 1 0 3 is a h u ma n rec o m bi na nt pr otei n. 
M ost I V T bi ol o gics pr o d uce oc ular i nfla m mati o n i n n o ncli nical test s pecies, a n d i nfla m mati o n 
was o bser ve d wit h G E M 1 0 3 i n c y n o m ol g us m o n ke ys.  I n ge neral, mil d, dr u g-i n d uce d 
i nfla m mati o n is c o nsi dere d t o be a n acce pta ble safet y ris k i n p osteri or se g me nt diseases, si nce it 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 2 6 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
is re versi ble, treata ble, a n d m o nit ora ble i n h u ma ns (S h ort 2 0 0 8 ).  De vel o p me nt of A D A will be 
m o nit ore d i n t he st u d y. 
T he P hase 1 si n gle asce n di n g d ose st u d y ( G E M- C L- 1 0 3 0 1) di d n ot ha ve a n y fi n di n gs of oc ular 
i nfla m mati o n f oll o wi n g d oses ra n gi n g fr o m 5 0 t o 5 0 0 m g a d mi nistere d i ntra vitreall y i n dr y 
A M D s u bjects.  F urt her m ore, t here were n o A D As detecte d i n t his st u d y, c o nsiste nt wit h t he 
e x pectati o n t hat a h u ma n pr otei n s h o ul d n ot elicit a n i m m u ne res p o nse i n h u ma n s u bjects. 
 
P ote nti al Ris ks of a nti- V E G F St a n d ar d of C are tre at me nt: 
O p ht hal m ol o gists are acc ust o me d t o pr o vi di n g fre q ue nt I V T i njecti o ns f or n A M D.  A re p ort b y 
t he A merica n Aca de m y of O p ht hal m ol o g y c o ncl u de d t hat i ntra vitreal a nti- V E G F 
p har mac ot hera p y is a safe a n d effecti ve treat me nt f or ne o vasc ular A M D o ver a 2- year peri o d 
(Ba kri 2 0 1 9 ).  A d verse oc ular e ve nts after I V T i njecti o n of a nti- V E G F a ge nts, i ncl u di n g 
e n d o p ht hal mitis, reti nal detac h me nt, a n d i ncrease d I O P are rare.  Arterial t hr o m b oe m b olic e ve nts 
i n ass ociati o n wit h use of a nti-
patie nts 
(Ba kri 2 0 1 9 ).  A rece nt p u blicati o n (Ba u mal, 2 0 2 0 ), reiterates t he i m p orta nce of effecti vel y 
ma na gi n g t he s pectr u m of i ntra oc ular i nfla m mati o n after treat me nt wit h a nti- V E G F a ge nts i n 
n A M D patie nts.  It is rec o m me n de d t hat as s o o n as a patie nt is dia g n ose d wit h i ntra oc ular 
i nfla m mati o n, reti nal vasc ulitis, a n d/ or a reti nal vasc ular occl usi ve e ve nt, a nti- V E G F treat me nt 
s h o ul d be s us pe n de d.  T he patie nt s h o ul d be m o nit ore d re g ularl y a n d f ut ure treat me nt o pti o ns f or 
n A M D ma y be deter mi ne d base d o n t he o utc o mes of t he a b o ve e ve nts a n d t he patie nt’s cli nical 
stat us.  T he cli nicia n ma y c o nsi der treat me nt m o dalities base d o n a n i n di vi d ualize d a p pr oac h a n d 
t he l ocall y a vaila ble S o C (Ba u mal, 2 0 2 0 ). 
 
P ote nti al Ris ks of G E M 1 0 3 t o get her wit h a nti- V E G F St a n d ar d of C are tre at me nt: 
C urre ntl y t here is n o n o ncli nical or cli nical i nf or mati o n o n effects of a d mi nisteri n g G E M 1 0 3 as 
a n a dj u nct t o a S o C afli berce pt t hera p y i ncl u di n g a n y p ote ntial si de effects.  H o we ver, I V T 
rec o m bi na nt h u ma n Fact or H has bee n use d i n a C N V m uri ne m o del i n c o m bi nati o n wit h a nti-
V E G F ( B orras 2 0 2 0 ). 
St u d y dr u g will n ot be i njecte d wit h ot her pr o d ucts i n t he sa me s yri n ge, as t he c o m pati bilit y of 
G E M 1 0 3 i n s ol uti o n wit h ot her pr o d ucts has n ot bee n e val uate d.  Afli berce pt is a d mi nistere d 
first, f oll o we d b y G E M 1 0 3 1 5 mi n utes ( ± 5 mi n utes) later (see Secti o n 6. 5. 2 ). 
 
Pr oce d ur al Ris ks:  I V T I njecti o n a n d A q ue o us H u m or S a m pli n g 
T he ris k of se vere c o m plicati o ns after I V T i njecti o n s uc h as u veitis, reti nal detac h me nt, 
A ver y 2 0 1 4 ).  
O p ht hal m ol o gists are acc ust o me d t o pr o vi di n g fre q ue nt ( m o nt hl y) I V T i njecti o ns f or n A M D, 
s o meti mes f or years.  A nteri or c ha m ber parace ntesis ( use d t o ac q uire a q ue o us h u m or sa m ples) 
has bee n wi del y use d a n d is c o nsi dere d safe, si m ple, a n d necessar y f or t he re d ucti o n of I O P i n a 
m ultit u de of e ye e mer ge ncies, i ncl u di n g ac ute a n gle cl os ure gla uc o ma, u veitis, h y p he ma, reti nal 
arter y occl usi o n, a n d e n d o p ht hal mitis i n or der t o pre ve nt f urt her irre versi ble visi o n l oss, 
es peciall y if use d i n c o nj u ncti o n wit h ot her me dical m o dalities. 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 2 7 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
P ote nti al Be nefit:  Rest or ati o n of C o m ple me nt Re g ul ati o n  
T he c urre nt S o C f or n A M D is I V T deli ver y of f u ncti o nal a nta g o nists of V E G F ( Sa h ni 2 0 2 0 , 
Jaffe 2 0 1 6).  H o we ver, t here are se veral practical li mitati o ns t o a nti- V E G F t hera p y, i ncl u di n g t he 
nee d f or fre q ue nt I V T i njecti o ns, i nc o m plete res p o nse, a n d/ or fail ure t o mai ntai n res p o nse i n 
s o me patie nts (Jaffe 2 0 1 6).  G E M 1 0 3 is i nte n de d t o b ot h rest ore a p pr o priate re g ulati o n of t he 
c o m ple me nt s yste m a n d t o hel p mai ntai n reti nal healt h.  I n vitr o a nal yses s u p p ort t he h y p ot hesis 
t hat G E M 1 0 3 rest ores a p pr o priate re g ulati o n b y bl oc ki n g A P h y peracti vit y a n d t he detri me ntal 
effects (e. g., i na p pr o priate cell l ysis, i m m u ne res p o nse) w hile retai ni n g t he be neficial effects 
(e. g., cleara nce of e xtracell ular de bris, re pair of o xi dati ve da ma ge) of p h ysi ol o gic c o m ple me nt 
acti vit y.  F u ncti o nal C F H als o has r oles i n t he oc ular c o m part me nt, i ncl u di n g assista nce i n R P E 
cleara nce of pr o d ucts of li pi d o xi dati o n a n d cell ular de bris t hat are necessar y t o mai ntai n 
h o me ostasis i n t he s u breti nal s pace, a n d w hic h are n o n-ca n o nical a n d se parate fr o m t he 
c o m ple me nt re g ulati o n pr o vi de d b y f u ncti o nal C F H ( Cali p pe 2 0 1 7 , Matta pallil 2 0 1 7 , Y u 2 0 2 0 ).  
T he be nefit of a t hera p y t hat ca n rest ore n or mal C F H a n d A P c o m ple me nt f u ncti o n, a n d w hic h 
has a n a bilit y t o a d dress R P E f u ncti o nal deficits i n n A M D patie nts is li kel y t o o ut wei g h t he 
a b o ve- me nti o ne d p ote ntial ris ks. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 2 9 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
O bjecti ves
 E n d p oi nts
 
Descri be t he eff ect o n L L V A 
 Mea n c ha n ge i n L L V A fr o m baseli ne i n E T D R S 
letters 
 
Descri be t he eff ect o n N EI- V F Q- 2 5  
 
Descri be t he eff ect o n M N Rea d 
 Mea n c ha n ge i n sc or e fr o m baseli ne o n 
N EI- V F Q- 2 5  
 Mea n c ha n ge i n ma xi m u m rea di n g s pee d fr o m 
baseli ne o n M N Rea d T est 
A b br e viati o ns: A D A =a nti dr u g a nti b o dies; A E =a d verse  e ve nt; B C V A = best c orr ecte d vis ual ac uit y; 
C F H =c o m ple me nt fact or H; C N V =c h or oi dal ne o vasc ularizati o n;  C P T =ce nter p oi nt t hic k ness;  C S T =c e ntral s u bfiel d 
t hic k ness; E T D R S = E arl y Tr eat me nt Dia betic Reti n o pat h y St u d y; F A =fl u or escei n a n gi o gr a p h y; F A F =f u n d us 
a ut ofl u or esce nce; I V T =i ntr a vitr eal; L L V A =l o w l u mi na nce vis ual ac uit y; M A = mac ular atr o p h y; 
M N Rea d = Mi n nes ot a L o w- visi o n Rea di n g T est; N EI- V F Q- 2 5 = Nati o nal E ye I nstit ute Vis ual F u ncti o ni n g 
Q uesti o n nair e- 2 5; O C T = o ptical c o her e nce t o m o gr a p h y; S D- O C T = S pectr al D o mai n O ptical C o her e nce 
T o m o gr a p h y; S o C = Sta n dar d of Car e ( 2 m g afli ber ce pt e ver y ot her m o nt h) 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 3 0 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
3  I N V E S TI G A TI O N A L P L A N 
3. 1  O ver all Desi g n a n d Pl a n of t he St u d y 
T his is a P hase 2a, si n gle- mas ke d, s ha m-c o ntr olle d, m ultice nter, m ulti ple- d ose st u d y i n s u bjects 
wit h n A M D t o e val uate t he safet y, t olera bilit y, i m m u n o ge nicit y, P K/ P D, c o m ple me nt 
bi o mar kers, a n d cli nical efficac y d uri n g 1 2 m o nt hs of G E M 1 0 3 I V T i njecti o ns E O M as a n 
a dj u nct t o S o C afli berce pt t hera p y. 
St u d y dr u g or s ha m, al o n g wit h S o C afli berce pt, will be a d mi nistere d t o 1 e ye o nl y, w hic h will 
be desi g nate d d uri n g t he scree ni n g pr ocess, base d o n eli gi bilit y, a n d pri or t o a n y baseli ne 
meas ure me nts.  See Secti o n 5. 4 f or deter mi nati o n of st u d y e ye. 
Detaile d assess me nts of I O P, V A a n d f u ncti o n, a n d reti nal para meters s uc h as C N V a n d M A 
lesi o n size will be perf or me d as descri be d i n t he sc he d ule of assess me nts ( S O A) i n A p pe n di x A . 
Data will be c ollecte d o n de m o gra p hics, me dical a n d oc ular hist or y, fa mil y hist or y, a n d 
c o nc o mita nt me dicati o ns.  A d diti o nall y, o p ht hal mic a nat o mic assess me nts a n d m ulti m o dal 
i ma gi n g, e x pl orat or y ge netic a n d bi o mar ker a nal yses, a n d a q ue o us h u m or sa m pli n g will be d o ne 
f or eac h s u bject e nr olle d. 
T he I n vesti gat or will m o nit or t he safet y of st u d y pr oce d ures acc or di n g t o l ocal i nstit uti o nal 
p olic y.  All A Es will be rec or de d i n t he electr o nic case re p ort f or m (e C R F). 
T he mi ni m u m pla n ne d d urati o n of eac h s u bject’s partici pati o n is a p pr o xi matel y 1 3 m o nt hs:  
1 m o nt h f or scree ni n g a n d 1 2 m o nt hs f or d osi n g a n d f oll o w- u p. 
3. 2  St u d y Desi g n a n d Criteri a f or D osi n g 
S u bjects will be ra n d o mize d t o 1 of 2 treat me nt gr o u ps:  G E M 1 0 3 + S o C or s ha m + S o C ( S o C 
defi ne d as 2 m g afli berce pt E O M).  See Secti o n 6. 6 f or ra n d o mizati o n of t he st u d y dr u g). 
All s u bjects treate d wit h G E M 1 0 3 will recei ve 5 0 0 μ g G E M 1 0 3 I V T, w hic h was t he hi g hest 
d ose teste d i n t he P hase 1 si n gle asce n di n g d ose st u d y i n dr y A M D ( G E M- C L- 1 0 3 0 1) a n d is t h us 
deter mi ne d t o be t he hi g hest t olera ble d ose t hat ac hie ve d s u pra p h ysi ol o gical le vels of G E M 1 0 3 
i n a q ue o us h u m or a n d was ass ociate d wit h P D acti vit y.  O ne d osi n g re gi me n ( E O M) will be 
e val uate d i n eac h treat me nt gr o u p.  A st u d y sc he matic is prese nte d i n Fi g ure 1 . 
Acc u m ulati n g safet y data will be re vie we d o n a n o n g oi n g basis ( See Secti o n 7. 4 ). 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 3 2 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
t otal of 6 I V T i njecti o ns will be a d mi nistere d o ver t he 1 2- m o nt h st u d y peri o d.  T he E O M I V T 
i njecti o n re gi me n of afli berce pt is use d i n sta n dar d cli nical d osi n g i n s u bjects wit h n A M D a n d is 
als o si milar t o t he d osi n g fre q ue nc y bei n g e val uate d i n ot her M A st u dies c o n d ucte d wit h a nti-
c o m ple me nt a ge nts (Lia o 2 0 2 0, Jaffe 2 0 2 0 ).  P K m o deli n g a n d si m ulati o n as well as oc ular P K 
data fr o m t he o n g oi n g P hase 1 si n gle asce n di n g d osi n g st u d y ( G E M- C L- 1 0 3 0 1) s u p p orts b ot h 
t he pr o p ose d d ose a n d d osi n g re gi me n of G E M 1 0 3 i n t his st u d y. 
3. 4  R ati o n ale f or D ose 
St u d y d ose rati o nale is descri be d i n Secti o n 1. 5. 1 . 
3. 5  St u d y E n d p oi nts 
St u d y e n d p oi nts are descri be d i n Ta ble 1 . 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 3 3 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
4  S T U D Y P O P U L A TI O N 
4. 1  T ar get P o p ul ati o n 
T he tar get p o p ulati o n f or t his st u d y is s u bjects wit h n A M D  w h o are u n der g oi n g treat me nt (at 
least 1 pri or d ose) wit h afli berce pt t hera p y. 
4. 2  N u m ber of S u bjects 
A p pr o xi matel y 4 5 s u bjects ( ~ 3 0 treate d wit h G E M 1 0 3 + S o C a n d ~ 1 5 treate d wit h s ha m + S o C; 
S o C defi ne d as afli berce pt E O M) are pla n ne d f or i ncl usi o n i n t he st u d y. 
4. 3  Eli gi bilit y Criteri a 
4. 3. 1  I ncl usi o n Criteri a 
S u bjects m ust meet all of t he f oll o wi n g i ncl usi o n criteria t o be c o nsi dere d f or partici pati o n: 
1.  At least 5 0 years ol d at t he ti me of si g ne d i nf or me d c o nse nt; s u bjects y o u n ger t ha n 
5 0 ma y be c o nsi dere d f or partici pati o n after c o ns ultati o n wit h t he Me dical M o nit or 
2.  C N V relate d t o n A M D wit h t he f oll o wi n g feat ures, as deter mi ne d b y t he I ma ge Rea di n g 
Ce nter 
a. Ma xi m u m C N V lesi o n size of 1 2 disc areas 
b.  S
 
3.  M ust be o n afli berce pt treat me nt pri or t o Da y 1 ( wit h at least o ne afli berce pt d ose 
recei ve d wit hi n 2 m o nt hs pri or t o Da y 1) A N D be a ble t o c o nti n ue afli berce pt at a n 
e ver y- ot her- m o nt h fre q ue nc y f or t he d urati o n of t he st u d y 
4.  B C V A i n t he st u d y e ye of 2 4 t o 7 5 letters usi n g t he Earl y Treat me nt Dia betic 
Reti n o pat h y St u d y ( E T D R S) C hart V A Scale (a p pr o xi matel y e q ui vale nt t o S nelle n V A of 
bet wee n 2 0/ 3 2 a n d 2 0/ 3 2 0) 
5.  S ufficie ntl y clear oc ular me dia, a de q uate p u pillar y dilati o n, fi xati o n t o per mit q ualit y 
f u n d us i ma gi n g, a n d a ble t o c o o perate s ufficie ntl y f or a de q uate o p ht hal mic vis ual 
f u ncti o n testi n g a n d a nat o mic assess me nt i n t he st u d y e ye 
6.  U n dersta n ds t he f ull nat ure a n d p ur p ose of t he st u d y, i ncl u di n g p ossi ble ris ks of st u d y 
pr oce d ures, a n d pr o vi des i nf or me d c o nse nt pri or t o i nitiati o n of a n y st u d y pr oce d ure 
7.  All s u bjects wit h re pr o d ucti ve p ote ntial m u st a gree t o use effecti ve c o ntrace pti ve 
met h o ds liste d i n Secti o n 4. 5. 2  t hr o u g h t he e n d of st u d y ( E O S) visit. 
4. 3. 2  E xcl usi o n Criteri a 
A s u bject w h o meets a n y of t he f oll o wi n g e xcl usi o n criteria will be i neli gi ble t o partici pate: 
1.  Prese nce of t he f oll o wi n g oc ular c o n diti o ns i n t he st u d y e ye: 
a. A n y acti ve oc ular disease or c o n diti o n t hat c o ul d c o nf o u n d t he assess me nt of t he 
mac ula or be a c o ntrai n dicati o n t o I V T i njecti o n, e. g., R P E tears or ri ps i n v ol vi n g 
t he mac ula, mac ular h ole (a n y sta ge, i ncl u di n g la mellar h ole), e pireti nal 
me m bra ne, M A or mac ul o pat hies d ue t o a n y disease ot her t ha n A M D, 
u nc o ntr olle d gla uc o ma (I O P of > 2 4 m m H g w he n o n 2 or m ore I O P-l o weri n g 
me dicati o ns), se vere gla uc o ma (c u p-t o-

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
gra de d as m o derate n o n pr oliferati ve dia betic reti n o pat h y or w orse ( wit h or 
wit h o ut dia betic mac ular e de ma) 
b.  A n y i ntra oc ular s ur ger y, e. g., a n y gla uc o ma s ur geries i ncl u di n g micr oi n vasi ve 
gla uc o ma s ur ger y a n d/ or a n y i ntra oc ular s ur ger y re q uiri n g vitrect o m y.  H o we ver, 
sta ble i ntra oc ular le ns re place me nt s ur ger y t hat was perf or me d m ore t ha n 
3 m o nt hs pri or t o c o nse nt will be all o we d. 
c. A p ha kia or c o m plete a bse nce of t he p osteri or ca ps ule 
d.  Pri or c or neal tra ns pla nt 
e. 
 
2.  Prese nce of a n y of t he f oll o wi n g oc ular c o n diti o ns i n eit her e ye: 
a. Hist or y of her petic i nfecti o n, i di o pat hic p ol y p oi dal c h or oi dal vasc ul o pat h y 
( P C V), pat h ol o gic m y o pia, ce ntral ser o us c h ori oreti n o pat h y ( C S C R), a d ult o nset 
f o veal patter n d ystr o p h y 
b.  C o nc urre nt disease t hat c o ul d re q uire me dical or s ur gical i nter ve nti o n d uri n g t he 
st u d y peri o d 
c. Acti ve/s us pecte d oc ular/ peri oc ular i nfecti o n or acti ve i ntra oc ular i nfla m mati o n 
d.  Hist or y of i di o pat hic or a ut oi m m u ne-ass ociate d u veitis ( gra di n g scale f or u veitis 
is a vaila ble i n A p pe n di x K ) 
3.  I n t he o pi ni o n of t he I n vesti gat or, t he s u bject has a n y pri or or o n g oi n g me dical c o n diti o n 
(e. g., oc ular ot her t ha n n A M D, s yste mic, ps yc hiatric) or cli nicall y si g nifica nt scree ni n g 
la b orat or y val ue t hat ma y prese nt a safet y ris k, i nterfere wit h st u d y c o m plia nce, i nterfere 
wit h c o nsiste nt st u d y f oll o w- u p, or c o nf o u n d data i nter pretati o n t hr o u g h o ut t he 
l o n git u di nal f oll o w- u p peri o d 
4.  S u bject has e x perie nce d a car di o vasc ular or cere br o vasc ular e ve nt wit hi n 1 2 m o nt hs of 
i nf or me d c o nse nt 
5.  Fe male s u bjects m ust n ot be pre g na nt or lactati n g, n or pla n t o bec o me pre g na nt d uri n g 
t he st u d y 
6.  C urre nt use of me dicati o ns k n o w n t o be t o xic t o t he le ns, reti na, or o ptic ner ve 
( defer o xa mi ne, c hl or o q ui ne/ h y dr o x yc hl or o q ui ne [ Pla q ue nil® ], ta m o xife n, p he n ot hiazi nes, 
et ha m b ut ol, di g o xi n, a n d a mi n o gl yc osi des).  ( C urre nt use is defi ne d as t he a d mi nistrati o n 
of first d ose of G E M 1 0 3 wit hi n 5 half-li ves of t he pr o hi bite d me dicati o n).  Past use of 
t hese me dicati o ns, wit h o ut hist or y of oc ular si de effects, is n ot c o nsi dere d e xcl usi o nar y.  
A p pe n di x L  pr o vi des a list of me dicati o ns t hat ma y p ote ntiall y e xacer bate mac ular e de ma 
or mac ular de ge nerati o n.  Use of t hese me dicati o ns is per mitte d if, i n t he o pi ni o n of t he 
I n vesti gat or, i n c o ns ultati o n wit h t he Me dical M o nit or, s uc h use will n ot c o nf o u n d t he 
i nter pretati o n of st u d y res ults. 
7.  Use of a n y i n vesti gati o nal ne w dr u g or ot her e x peri me ntal treat me nt i n t he last 6 m o nt hs 
pri or t o Da y 1, a n d/ or recei pt at a n y ti me of a n y pri or ge ne t hera p y (e g A de n o-ass ociate d 

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
vir us), cell t hera p y, or oc ular de vice i m pla ntati o n ( ot her t ha n p osteri or c ha m ber 
i ntra oc ular le ns place me nt after cataract s ur ger y) 
4. 4  Met h o d f or Assi g ni n g S u bjects t o Tre at m e nt Gr o u ps 
S u bjects will be ra n d o ml y assi g ne d t o a treat me nt c o h ort i n a 2: 1 ra n d o mizati o n patter n wit h 
2 s u bjects assi g ne d t o treat me nt wit h G E M 1 0 3 + S o C ( S o C defi ne d as afli berce pt E O M) f or e ver y 
1 s u bject assi g ne d t o treat me nt wit h s ha m + S o C. 
4. 5  S u bject Restricti o ns D uri n g t he St u d y 
4. 5. 1  Ge ner al a n d Diet ar y 
N ot a p plica ble. 
4. 5. 2  C o ntr ace pti o n a n d Pre g n a nc y A v oi d a nce Pr oce d ures 
If of c hil d beari n g p ote ntial (all fe male s u bjects u nless a me n orr heic f or > 1 year or ha ve 
u n der g o ne s ur gical sterilizati o n), s u bjects are re q uire d t o practice at least 2 me dicall y a p pr o ve d 
a n d hi g hl y effecti ve met h o ds of c o ntrace pti o n ( defi ne d as t h ose w hic h res ult i n a l o w fail ure rate 
 
All fe male s u bjects of c hil d beari n g p ote ntial m ust ha ve a ne gati ve pre g na nc y test at scree ni n g 
a n d bef ore d osi n g wit h st u d y dr u g.  W o me n of c hil d beari n g p ote ntial m ust a gree t o a bstai n fr o m 
heter ose x ual se x ual i nterc o urse fr o m date of i nf or me d c o nse nt, a n d at a mi ni m u m t hr o u g h t he 
3 m o nt hs after t he last I V T i njecti o n, or a gree t o c o nsiste ntl y use at least 2 of a n y of t he 
f oll o wi n g met h o ds of c o ntrace pti o n fr o m date of i nf or me d c o nse nt a n d f or at least 3 m o nt hs after 
t he last I V T i njecti o n:  c o n d o ms ( male or fe male) wit h s per mici de, dia p hra g m wit h s per mici de, 
cer vical ca p wit h s per mici de, i ntra uteri ne de vice, h or m o nal c o ntrace pti o n (e. g., oral or patc h 
c o ntrace pti ves, N or pla nt ® , De p o- Pr o vera® ), or ot her 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 c o ntrace pti ve met h o d desi g ne d t o pr otect a gai nst pre g na nc y.  Peri o dic 
a bsti ne nce (e. g., cale n dar, o v ulati o n, s y m pt ot her mal, p ost- o v ulati o n met h o ds) a n d wit h dra wal 
are n ot acce pta ble met h o ds of c o ntrace pti o n. 
Male s u bjects m ust a gree t o c o nsiste ntl y use a p pr o priate c o ntrace pti o n a n d t o refrai n fr o m s per m 
d o nati o n fr o m c o nse nt t hr o u g h 3 m o nt hs after t he fi nal d ose. 
S u bjects will be pr o vi de d wit h i nf or mati o n o n acce p ta ble met h o ds of c o ntrace pti o n as part of t he 
s u bject i nf or me d c o nse nt pr ocess a n d will be as ke d t o si g n a n i nf or me d c o nse nt f or m (I C F) 
stati n g t hat t he y u n dersta n d t he re q uire me nts f or acce pta ble meas ures of birt h c o ntr ol. 
4. 6  C o nc o mit a nt Me dic ati o ns a n d Tre at m e nts 
C o nc o mita nt me dicati o ns i ncl u de prescri pti o n a n d o ver-t he-c o u nter me dicati o ns, pr o p h ylactic 
a n d t hera pe utic vacci nes, her bal me dicati o ns, vita mi ns, a n d dietar y/ n utriti o nal s u p ple me nts, as 
well as a n y i n vesti gati o nal me dicati o ns t he s u bject ma y ha ve recei ve d.  See A p pe n di x L  f or a list 
of me dicati o ns t hat ma y p ote ntiall y e xacer bate mac ular e de ma or mac ular de ge nerati o n.  
C o nc o mita nt treat me nts i ncl u de dia g n ostic, palliati ve, or i nter ve nti o nal pr oce d ures (e. g., 
he mat o p oietic ste m cell tra ns pla nt, b o ne marr o w tra ns pla nt). 
At t he scree ni n g visit, i nf or mati o n o n all me dicati o ns a n d treat me nts recei ve d b y t he s u bject 
wit hi n t he prece di n g 4 wee ks will be rec or de d.  T hereafter, reas o na ble eff orts will be ma de t o 
ascertai n all c ha n ges i n c o nc o mita nt me dicati o ns a n d treat me nts fr o m scree ni n g u ntil t he s u bject 
c o m pletes t he E O S visit.  S u bjects w h o are o n a sta ble d osi n g re gi me n f or a n y of t he me dicati o ns 
liste d i n A p pe n di x L at t he ti me of scree ni n g, ma y be e nr olle d a n d re mai n o n t he d osi n g re gi me n 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
d uri n g t he st u d y if, i n t he o pi ni o n of t he I n vesti gat or, s uc h use will n ot c o nf o u n d t he 
i nter pretati o n of st u d y res ults.  If d uri n g t he c o urse of t he st u d y a s u bject de vel o ps a c o n diti o n 
t hat re q uires treat me nt wit h o ne of t he me dicati o ns liste d i n A p pe n di x L , t he s u bject s h o ul d be 
treate d as cli nicall y i n dicate d; h o we ver, t he Me dical M o nit or m ust be c o ns ulte d pri or t o 
c o nti n ui n g treat me nt i n t he st u d y.  I nf or mati o n o n all c o nc o mita nt me dicati o ns a n d treat me nts 
will be rec or de d i n t he e C R F a n d will i ncl u de t he na me of t he me dicati o n ( bra n d or ge neric) or 
t hera p y, reas o n f or use, start date, a n d st o p date. 
D uri n g t he c o urse of t he st u d y, if i n t he o pi ni o n of t he I n vesti gat or, t he pr ot oc ol re q uire d d osi n g 
of afli berce pt e ver y 6 0 da ys is i ns ufficie nt f or ma na gi n g t he s u bject’s cli nical c o n diti o n, 
a d diti o nal d oses of afli berce pt ma y be a d mi nistere d as nee de d.  T he Me dical M o nit or s h o ul d be 
n otifie d t hat a d diti o nal d osi n g has bee n a d mi nistere d ( per missi o n d oes n ot nee d t o be re q ueste d 
pri or t o treat me nt), a n d all d oses of afli berc e pt a d mi nistere d m ust be d oc u me nte d. 
4. 7  Disc o nti n u ati o n of S u bjects 
4. 7. 1  Pre m at ure Wit h dr a w al fr o m St u d y P artici p ati o n 
S u bjects ha ve t he ri g ht t o wit h dra w fr o m t he st u d y at a n y ti me f or a n y reas o n. 
T he I n vesti gat or ca n als o wit h dra w a s u bject u p o n t he re q uest of t he S p o ns or or if t he S p o ns or 
ter mi nates t he st u d y.  U p o n occ urre nce of a seri o us or i nt olera ble A E, t he I n vesti gat or will 
c o nfer wit h t he S p o ns or or desi g nee.  If a s u bject is disc o nti n ue d beca use of a n A E, t he e ve nt 
will be f oll o we d u ntil it is res ol ve d or u ntil sta ble, or t he S p o ns or a n d I n vesti gat or a gree t hat 
f urt her f oll o w- u p is n ot nee de d (Secti o n 7 ). 
4. 7. 2  Pr oce d ures f or Disc o nti n u ati o n 
If a s u bject disc o nti n ues at a n y ti me after bei n g treate d wit h G E M 1 0 3 or s ha m, all eff orts s h o ul d 
be ma de t o ha ve t he s u bject c o m plete t he f oll o w- u p visit pr oce d ures, i ncl u di n g E O S/ Earl y 
Wit h dra wal visit as per t he S O A ( A p pe n di x A ).  All s u bjects w h o wit h dra w will be as ke d a b o ut 
t he reas o n(s) f or t heir disc o nti n uati o n a n d a b o ut t he prese nce of a n y A Es.  T he date a n d t he 
reas o n f or disc o nti n uati o n will be rec or de d i n t he e C R F. 
W he n a s u bject fails t o ret ur n f or sc he d ule d assess me nts, t he f oll o wi n g eff orts s h o ul d be ma de t o 
c o ntact hi m/ her t o deter mi ne a reas o n f or t he fail ure t o ret ur n:  3 p h o ne atte m pts, i ncl u di n g t he 
date a n d ti me, will be d oc u me nte d i n t he s u bject’s c hart.  If t here is n o res p o nse t o t he tele p h o ne 
calls, a certifie d letter will be se nt.  After t hese eff orts ha ve bee n c o m plete d, a s u bject will be 
c o nsi dere d as l ost t o f oll o w- u p.  All atte m pts at c o ntact s h o ul d be d oc u me nte d i n t he s u bject’s 
me dical rec or d. 
4. 8  S u bject Re pl ace m e nt P olic y 
All s u bjects w h o recei ve at least 1 d ose of G E M 1 0 3 or refere nce t hera p y (s ha m) will be i ncl u de d 
i n s u m maries of safet y res ults.  I n t his se nse, treate d s u bjects are n ot “re place d.” 
If a s u bject disc o nti n ues fr o m t he st u d y bef ore c o m pleti n g 3 d oses, t he S p o ns or ma y c h o ose t o 
e nr oll a d diti o nal s u bjects . 
4. 9  S u bject Rescree ni n g 
D uri n g t he 3 5- da y scree ni n g peri o d, s u bjects will be all o we d t o retest a scree ni n g pr oce d ure(s) 
wit h a p pr o val fr o m t he S p o ns or a n d Me dical M o nit or.  Retests be y o n d t he 3 5- da y wi n d o w will 
re q uire t he s u bject t o be rec o nse nte d. 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
5  S T U D Y P R O C E D U R E S 
5. 1  St u d y Assess m e nts 
T he S O A is prese nte d i n A p pe n di x A.   T he S O A pr o vi des detaile d i nf or mati o n re gar di n g t he 
ti me p oi nts f or all of t hese assess me nts. 
5. 1. 1  I nf or me d C o nse nt 
T he I n vesti gat or is re q uire d t o o btai n i nf or me d c o nse nt acc or di n g t o t his pr ot oc ol a n d 
a p pr o priate l ocal re q uire me nts a n d re g ulati o ns pri or t o e nr olli n g a s u bject i n t his st u d y.  A c o p y 
of t he si g ne d a n d date d I C F will be gi ve n t o t he s u bject.  T he ori gi nal f or m s hall be mai ntai ne d 
i n t he s u bject’s me dical rec or ds at t he site.  If t he I C F is re vise d d uri n g t he c o urse of t he st u d y, 
sites will rec o nse nt all acti ve partici pati n g s u bjects. 
5. 1. 2  Ge netic S a m ple C ollecti o n 
All s u bjects will pr o vi de a w h ole bl o o d sa m ple f or e x pl orat or y ge netics pri or t o t heir first st u d y 
dr u g d ose.  Refer t o t he la b orat or y ma n ual f or f urt her details.  T he sa m ples will be se nt t o a 
c o ntract la b orat or y selecte d b y t he S p o ns or f or tar gete d se q ue nci n g usi n g t he S p o ns or’s ge netic 
testi n g assa y (Secti o n 5. 2. 1 ). 
5. 1. 3  Me dic al a n d Oc ul ar Hist or y 
A me dical hist or y f or t he past 6 m o nt hs, pl us a n y si g nifica nt, rele va nt me dical hist or y s uc h as 
pri or car di o vasc ular e ve nts, dia betes mellit us, or ca ncer will be o btai ne d f or eac h s u bject at 
scree ni n g.  C o n diti o ns o n g oi n g at baseli ne will be d oc u me nte d.  S ocial hist or y, t o i ncl u de 
s m o ki n g hist or y a n d use of m ulti vita mi n s u p ple me nts, will als o be o btai ne d. 
A n o p ht hal mic me dical hist or y will be o btai ne d t o i ncl u de a n y past or c urre nt oc ular c o n diti o ns, 
s ur geries, a n d s y m pt o ms, as well as c o n diti o ns f or w hic h t he s u bject is u n der g oi n g pre-e m pti ve 
o bser vati o n, e. g., gla uc o ma scree ni n g.  S pecificall y, a n y hist or y of A M D i ncl u di n g hist or y of 
I V T i njecti o ns will be ca pt ure d.  S u bjects will als o be re q ueste d t o pr o vi de a fa mil y o p ht hal mic 
hist or y if a vaila ble. 
Refer t o Secti o n 4. 6  f or details o n c ollecti o n of me dicati o n hist or y a n d c o nc o mita nt 
me dicati o ns/treat me nts. 
5. 1. 4  De m o gr a p hic I nf or m ati o n 
T he f oll o wi n g de m o gra p hic i nf or mati o n will be c ollecte d at scree ni n g acc or di n g t o l ocal 
re g ulati o ns:  date of birt h, ge n der, race, a n d et h nicit y. 
5. 1. 5  P h ysic al E x a mi n ati o n 
P h ysical e xa mi nati o ns will be perf or me d b y t he I n vesti gat or or q ualifie d desi g nee at t he 
ti me p oi nts s pecifie d i n t he S O A i n A p pe n di x A .  C o m plete p h ysical e xa mi nati o ns will i ncl u de 
a n assess me nt of t he s u bject’s ge neral a p peara nce; s ki n, H E E N T ( hea d, e yes, ears, n ose, t hr oat), 
heart, l u n gs, a b d o me n, e xtre mities/j oi nts, a n d ne ur ol o gical stat us.  A 1 2-lea d electr ocar di o gra m 
( E C G) will be ta ke n at scree ni n g, after l yi n g s u pi ne f or 5 mi n utes, as part of t he car diac 
e xa mi nati o n.  A b n or mal fi n di n gs will be rec or de d i n t he e C R F a n d referre d f or a p pr o priate 
i n vesti gati o n b y a pri mar y care p h ysicia n or ot her healt hcare pr o vi der at t he deter mi nati o n of t he 
I n vesti gat or. 

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Pa ge 3 8 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
5. 1. 6  O p ht h al mic E x a mi n ati o n 
A c o m pre he nsi ve o p ht hal mic e xa mi nati o n of b ot h t he st u d y a n d fell o w e ye will be perf or me d b y 
t he I n vesti gat or or q ualifie d desi g nee at t he ti me p oi nts s pecifie d i n t he S O A i n A p pe n di x A.   
T hese e xa mi nati o ns will i ncl u de a n assess me nt of t he V A ( b ot h B C V A a n d L L V A) a n d vis ual 
f u ncti o n, a c o m plete o p ht hal mic bi o micr osc o p y e xa mi nati o n i ncl u di n g f u n d us e xa mi nati o n, I O P 
( pretreat me nt I O P is re q uire d O U, p ost treat me nt I O P is o nl y re q uire d i n t he S E), a n d oc ular 
i ma gi n g tests t o vis ualize t he a p peara nce a n d pat h ol o g y of t he reti na a n d ass ociate d oc ular 
tiss ues.  All fi n di n gs will be rec or de d i n t he e C R F.  F urt her details o n t hese e xa mi nati o ns are 
f o u n d i n res pecti ve st u d y ma n uals. 
O n d osi n g da ys, I O P assess me nts are o btai ne d pri or t o t he d ose O U, a n d 3 0 ± 1 5 mi n utes after t he 
d ose o nl y i n t he S E ( O U o pti o nal).  A n a d diti o nal assess me nt fr o m t he S E s h o ul d be ta ke n at 
6 0 ±
 m m H g at t he 3 0- mi n ute assess me nt.  If t he 
I O P c o nti n ues t o e xcee d 3 0 m m H g, t he n sta n dar d I O P-l o weri n g i nter ve nti o ns ( per i nstit uti o nal 
i nstit uti o nal g ui deli nes.  Re gar dless of w het her a p pla nati o n t o n o metr y or a T o n o- Pe n®  is use d t o 
meas ure I O P, t he sa me met h o d s h o ul d be use d f or t he s u bject f or t he e ntiret y of t heir 
partici pati o n i n t his st u d y. 
5. 1. 7  Vit al Si g n Me as ure me nts 
Vital si g n meas ure me nts will i ncl u de s yst olic a n d diast olic bl o o d press ures, heart rate, 
res pirat or y rate, a n d b o d y te m perat ure.  T he s u bject will be seate d f or at least 5 mi n utes bef ore 
all meas ure me nts are ta ke n.  Vital si g ns will be meas ure d at t he ti me p oi nts i n dicate d i n t he S O A 
i n A p pe n di x A . 
W he n pr oce d ures o verla p a n d are sc he d ule d t o occ ur at t he sa me ti me p oi nt, vital si g ns s h o ul d be 
assesse d pri or t o a n y bl o o d c ollecti o n. 
Ma na ge me nt of s u bject safet y re gar di n g vital si g ns, i ncl u di n g t he a p pr o priate ness of d osi n g if 
vital si g ns are o ut of ra n ge, is t he res p o nsi bilit y of t he I n vesti gat or.   
5. 2  Cli nic al L a b or at or y Assess m e nts 
A list of all cli nical la b orat or y tests t hat will be perf or me d, as well as t he ti me p oi nts f or sa m ple 
c ollecti o n, are s pecifie d i n t he S O A i n A p pe n di x A . 
Ce ntral la b orat or y refere nce ra n ges will be use d t hr o u g h o ut t he st u d y.  All re q uire d tests will be 
perf or me d b y a q ualifie d la b orat or y. 
Cli nical la b orat or y sa m ples will be st ore d b y t he S p o ns or or desi g nee i n a sec ure a n d c o ntr olle d 
e n vir o n me nt u ntil a nal ysis a n d will be destr o ye d b y t he S p o ns or or desi g nee after all o bli gati o ns 
ha ve bee n met, or s o o ner if re q uire d b y l ocal re g ulati o ns. 
Refer t o t he la b orat or y ma n ual f or f urt her details re gar di n g t he c ollecti o n, pr ocessi n g, a n d 
st ora ge of cli nical la b orat or y sa m ples. 
5. 2. 1  D N A S a m ple 
After c o nse nt is pr o vi de d a n d pri or t o d osi n g, a w h ole bl o o d sa m ple will be c ollecte d fr o m eac h 
s u bject f or D N A e xtracti o n (Secti o n 5. 1. 2 ). 
D N A se q ue nces, i ncl u di n g b ot h t he pr otei n c o di n g se q ue nces a n d t he n o nc o di n g se q ue nces 
i n v ol ve d i n tra nscri pti o nal a n d tra nslati o nal re g ulati o n, a n d ot her bi ol o gical f u ncti o ns, will be 

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
a nal yze d b y t he S p o ns or f or ge netic m o dificati o ns t hat ma y c o ntri b ute t o a n d/ or m o dif y t he 
disease p he n ot y pe or rate of pr o gressi o n of n A M D.  S uc h D N A se q ue nces, w hic h ma y be 
i n vesti gate d i ncl u de, b ut are n ot li mite d t o t he f oll o wi n g:  ge n o me- wi de ass ociate d varia nts f or 
A M D ris k a n d/ or pr o gressi o n, a n d selecte d pr otei n c o di n g varia nts i n ge nes near s uc h 
ge n o me- wi de ass ociati o n si g nals. 
D N A sa m ples will be st ore d b y t he S p o ns or, or desi g nee, i n a sec ure a n d c o ntr olle d e n vir o n me nt 
u ntil a nal ysis, a n d will be destr o ye d b y t he S p o ns or after all o bli gati o ns ha ve bee n met, or s o o ner 
if re q uire d b y l ocal re g ulati o ns or if re q ueste d i n writi n g b y t he s u bject. 
Refer t o A p pe n di x B  a n d t he la b orat or y ma n ual f or f urt her details re gar di n g t he c ollecti o n, 
pr ocessi n g, a n d st ora ge of t hese sa m ples. 
5. 2. 2  E x pl or at or y Bi o m ar k ers 
Bl o o d sa m ples f or plas ma is olati o n will be o btai ne d at t he ti me p oi nts s pecifie d i n t he S O A f or 
e x pl orat or y a nal yses t o i de ntif y a n d e val uate disease-relate d bi o mar kers, w here l ocal re g ulati o ns 
a n d bl o o d v ol u me per mits (see A p pe n di x A ).  A s pecific sa m ple f or e x pl orat or y bi o mar ker 
a nal ysis is bei n g c ollecte d i n t his st u d y; h o we ver, re mai ni n g bl o o d sa m ples c ollecte d i n t his 
st u d y ma y als o be use d t o a nal yze a d diti o nal bi o mar kers of p ote ntial cli nical i nterest, if t here is 
s ufficie nt sa m ple a n d w here l ocal re g ulati o ns per mit. 
A q ue o us h u m or sa m ples will be o btai ne d at t he ti me p oi nts s pecifie d i n t he S O As f or e x pl orat or y 
a nal yses t o i de ntif y a n d e val uate disease-relate d bi o mar kers (see A p pe n di x A ).  A q ue o us h u m or 
sa m ples c ollecte d will be o btai ne d f or t he pri mar y p ur p ose of P D bi o mar ker a nal ysis. 
C ollecti o n of sa m ples f or e x pl orat or y bi o mar ker a nal ysis will be s u bject t o discreti o nar y 
a p pr o val fr o m eac h ce nter’s I nstit uti o nal Re vie w B oar d (I R B)/I n de pe n de nt Et hics C o m mittee 
(I E C) a n d t he s pecific writte n c o nse nt of t he s u bject.  T his secti o n of t he pr ot oc ol o nl y a p plies if 
a p pr o val f or c ollecti o n of t hese a d diti o nal sa m ples has bee n gra nte d b y t he I R B/I E C a n d c o nse nt 
is pr o vi de d b y t he s u bject. 
Sa m ples will be st ore d b y t he S p o ns or or desi g nee i n a sec ure a n d c o ntr olle d e n vir o n me nt u ntil 
a nal ysis.  T he y will be destr o ye d b y t he S p o ns or or desi g nee after all o bli gati o ns ha ve bee n met, 
or s o o ner if re q uire d b y l ocal re g ulati o ns. 
Refer t o t he la b orat or y ma n ual f or f urt her details re gar di n g t he c ollecti o n, pr ocessi n g, a n d 
st ora ge of t hese sa m ples. 
5. 2. 3  P K a n d I m m u n o ge nicit y Assess me nts 
A q ue o us h u m or sa m ples will be c ollecte d f or P K (assesse d as t otal C F H c o nce ntrati o n i n 
a q ue o us h u m or)/ P D.  Bl o o d sa m ples will be c ollecte d f or A D A e val uati o n at t he ti me p oi nts 
s pecifie d i n A p pe n di x A  a n d i n t he la b orat or y ma n ual. 
5. 3  I m a gi n g Assess m e nts 
C ol or f u n d us p h ot o gra p h y ( A p pe n di x C ), f u n d us a ut ofl u oresce nce ( F A F; A p pe n di x D ), 
fl u orescei n a n gi o gra p h y ( F A; A p pe n di x E ), s pectral d o mai n – o ptical c o here nce t o m o gra p h y 
( O C T; A p pe n di x F ), o ptical c o here nce t o m o gra p h y – a n gi o gra p h y ( O C T- A; A p pe n di x G ), a n d 
near i nfrare d reflecta nce i ma gi n g ( A p pe n di x H ) will be e val uate d at t he ti me- p oi nts s pecifie d i n 
A p pe n di x A . 
F ull i nstr ucti o ns o n i ma ge ac q uisiti o n a n d a nal ysis will be pr o vi de d i n t he i ma gi n g ma n ual(s). 

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
5. 4  Deter mi n ati o n of St u d y E ye 
O nl y 1 e ye will be selecte d as t he st u d y e ye.  If b ot h e yes meet all e ye-s pecific e ntr y criteria, 
t he n t he st u d y e ye will be deter mi ne d b y t he I n vesti gat or a n d t he s u bject t o get her.  All 
assess me nts will be perf or me d i n t he st u d y e ye as well as t he fell o w e ye w he ne ver feasi ble. 
Si nce st u d y e ye selecti o n is base d o n b ot h V A a n d i ma gi n g assess me nts, t his deter mi nati o n will 
be ma de after res ults f or scree ni n g assess me nts are a vaila ble, b ut bef ore t he baseli ne visit a n d 
ra n d o mizati o n. 

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
6  S T U D Y T R E A T M E N T S 
6. 1  Tre at m e nts A d mi nistere d 
6. 1. 1  D ose A dj ust me nts 
D ose a dj ust me nts are n ot pla n ne d f or i n di vi d ual s u bjects.  A dj ust me nts t o d ose le vel a n d/ or 
fre q ue nc y ma y be i m ple me nte d base d o n re vie w of e mer gi n g data. 
6. 1. 2  D ose Esc al ati o n 
D ose escalati o n is n ot pla n ne d f or i n di vi d ual s u bjects. 
6. 2  St o p pi n g R ules 
6. 2. 1  St o p pi n g R ules i n I n di vi d u al S u bjects 
If a s u bject e x perie nces a n S A E c o nsi dere d relate d t o G E M 1 0 3, t he s u bject’s d osi n g will be 
pa use d u ntil t he S A E has res ol ve d, or u ntil t he I n vesti gat or deci des, i n c o ns ultati o n wit h t he 
S p o ns or, t hat t he s u bject ma y c o nti n ue wit h st u d y dr u g. 
6. 2. 2  St o p pi n g R ules f or M ulti ple S u bjects 
u ne x pecte d seri o us a d verse reacti o n ( S U S A R), t he S p o ns or will c o n ve ne t he Me dical Re vie w 
C o m mittee ( M R C, see Secti o n 7. 4 ) t o deter mi ne w het her t o c o nti n ue t he st u d y i n a ma n ner s uc h 
t hat be nefits o ut wei g h ris ks, or t o cease f urt her e nr oll me nt.  T he S p o ns or will c o n d uct o n g oi n g 
re vie ws f or detecti o n of p ote ntial safet y si g nals.  At a n y ti me d uri n g t his st u d y, if a cli nicall y 
rele va nt si g nal is esta blis he d, t he S p o ns or ma y re q uest a pa use i n d osi n g t o re vie w re p orte d 
safet y e ve nts a n d all a vaila ble data.  If a pa use is i nstit ute d, d osi n g ma y res u me o nl y after re vie w 
of a vaila ble data b y t he M R C. 
6. 3  Descri pti o n of St u d y Dr u g 
T he refere nce d oc u me nt f or G E M 1 0 3 is t he I n vesti gat or’s Br oc h ure.  G E M 1 0 3 m ust be 
a d mi nistere d u n der cl ose s u per visi o n of t he I n vesti gat or, or desi g nee. 
T he st u d y dr u g will be pr o vi de d i n sterile, si n gle- use vials as a 1 0 m g/ m L c o nce ntrate d li q ui d.  
T he dr u g pr o d uct ma y be ase pticall y dil ute d t o t he a p pr o priate d ose c o nce ntrati o n acc or di n g t o 
t he pr oce d ures o utli ne d i n t he p har mac y ma n ual as necessar y. 
A d diti o nal details are pr o vi de d i n  Secti o n 1. 2 . 
6. 4  St or a ge a n d Dis p ositi o n of St u d y Dr u g 
6. 4. 1  Recei pt of Dr u g S u p plies 
U p o n recei pt of t he st u d y treat me nt s u p plies, a n  i n ve nt or y m ust be perf or me d, a n d a dr u g recei pt 
l o g fille d o ut a n d si g ne d b y t he pers o n acce pti n g t he s hi p me nt.  Recei pt of st u d y dr u g a n d u pl oa d 
of s hi p me nt te m perat ure m o nit or re p orts m ust als o occ ur i n t he a p pr o priate I R T s yste m i n or der 
t o ma ke t he st u d y dr u g a vaila ble f or dis pe nsati o n.  It is i m p orta nt t hat t he desi g nate d st u d y staff 
c o u nts a n d verifies t hat t he s hi p me nt c o ntai ns all t he ite ms n ote d i n t he s hi p me nt i n ve nt or y.  A n y 
da ma ge d or u n usa ble G E M 1 0 3 vials i n a gi ve n s hi p me nt will be d oc u me nte d i n t he st u d y files.  
If a n y part of a n i n vesti gati o nal me dici nal pr o d uct kit is da ma ge d, t he e ntire kit will be re place d.  
T he I n vesti gat or m ust n otif y t he S p o ns or of a n y da ma ge d or u n usa ble st u d y treat me nts t hat were 
s u p plie d t o t he I n vesti gat or’s site. 

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
6. 4. 2  M a n a ge me nt of Cli nic al S u p plies 
T he S p o ns or will pr o vi de t he I n vesti gat or a n d st u d y site wit h a de q uate q ua ntities of G E M 1 0 3.  
G E M 1 0 3 will be la bele d “f or cli nical trial use” a n d ha ve all re q uire d la beli n g per re g ulati o ns.  
Eac h vial will be i n di vi d uall y la bele d f or f ut ure s u bject i de ntificati o n p ur p oses. 
G E M 1 0 3 will be s u p plie d i n si n gle- use vials wit h a 0. 2 5 m L fill v ol u me at a c o nce ntrati o n of 
1 0 m g/ m L C F H.  T he st u d y site p har mac y pers o n nel will pre pare a si n gle d ose f or eac h s u bject.  
A p har mac y ma n ual will be ma de a vaila ble a n d trai ni n g pr o vi de d t o e ns ure p har mac y staff ca n 
c o m pl y wit h all dr u g st ora ge, pre parati o n, a d mi nistrati o n, a n d dr u g acc o u nta bilit y pr oce d ures. 
6. 4. 3  St or a ge 
G E M 1 0 3 m ust be st ore d i n a sec ure area wit h li mite d access, pr otecte d fr o m m oist ure a n d li g ht, 
a n d be st ore d at 5° C ± 3° C ( 2- 8° C).  T he refri gerat or s h o ul d ha ve a n a ut o mate d te m perat ure 
rec or di n g a n d alert s yste m.  I n ad diti o n, dr u g acc o u nta bilit y st u d y pers o n nel are re q uire d t o kee p 
a te m perat ure l o g t o esta blis h a rec or d of c o m plia nce wit h t hese st ora ge c o n diti o ns.  O nl y dr u g 
acc o u nta bilit y pers o n nel s h o ul d ha ve access t o t he pr o d uct use d i n t his st u d y. 
6. 4. 4  Dis p ositi o n 
T he I n vesti gat or or desi g nee will be res p o nsi ble f or mai ntai ni n g acc urate rec or ds f or all s u p plies 
use d.  O pe ne d vials of G E M 1 0 3 c o ntai ni n g resi d ual v ol u me will u n der g o G E M 1 0 3 
acc o u nta bilit y/rec o nciliati o n.  F oll o wi n g G E M 1 0 3 acc o u nta bilit y, t he S p o ns or will pr o vi de 
a ut h orizati o n t o t he I n vesti gat or t o ret ur n or destr o y a n y re mai ni n g i n vesti gati o nal pr o d uct as 
descri be d i n Secti o n 6. 7 . 
U n der n o circ u msta nces will G E M 1 0 3 be use d ot her t ha n as directe d i n t he pr ot oc ol.  Refer t o 
t he p har mac y ma n ual f or a d diti o nal details. 
T he site is res p o nsi ble f or re p orti n g t o t he site m o nit or a n d t o t he a p pr o priate S p o ns or 
re prese ntati ve a n y vials of G E M 1 0 3 t hat were n ot te m perat ure-c o ntr olle d d uri n g s hi p me nt or 
d uri n g st ora ge.  S uc h vials will be retai ne d f or i ns pecti o n b y t he site m o nit or a n d ne xt ste ps will 
be disc usse d wit h t he S p o ns or’s S u p pl y Ma na ger.  Vials deter mi ne d t o be q uesti o na ble or 
u ns uita ble ma y be q uara nti ne d or dis p ose d of u p o n a p pr o val b y t he S p o ns or acc or di n g t o 
a p pr o ve d met h o ds. 
It is t he I n vesti gat or’s res p o nsi bilit y t o e ns ure t hat t hat t he p har mac y pers o n nel mai ntai n acc urate 
rec or ds of recei pt of all G E M 1 0 3 vials, i ncl u di n g dates of recei pt.  I n a d diti o n, acc urate rec or ds 
will be ke pt re gar di n g w he n a n d h o w m uc h G E M 1 0 3 is dis pe nse d a n d use d b y eac h s u bject i n 
t he st u d y (i ncl u di n g d oc u me ntati o n of eac h dil uti o nal rec or d use d t o pre pare t he dr u g f or 
i njecti o n).  Reas o ns f or de part ure fr o m t he e x pecte d dis pe nsi n g re gi me n m ust als o be rec or de d.  
T o satisf y re g ulat or y re q uire me nts re gar di n g dr u g acc o u nta bilit y, all G E M 1 0 3 vials will be 
rec o ncile d a n d retai ne d u ntil st u d y c o ncl usi o n.  At t hat ti me, G E M 1 0 3 vials will be destr o ye d or 
ret ur ne d t o t he S p o ns or acc or di n g t o a p plica ble re g ulati o ns. 
6. 5  Pre p ar ati o n a n d A d mi nistr ati o n of St u d y Dr u g 
6. 5. 1  Pre p ar ati o n of St u d y Dr u g 
D ose pre parati o n a n d a d mi nistrati o n s h o ul d be perf or me d usi n g sterile, n o n p yr o ge nic dis p osa ble 
materials i ncl u di n g, b ut n ot restricte d t o s yri n ges, nee dles, tra nsfer t u bi n g, a n d st o pc oc ks. 
T w o s yri n ges will be pre pare d: 1 f or afli berce pt a n d 1 f or G E M 1 0 3/s ha m.  I njecti o ns will be 
ma de wit h 2 se parate s yri n ges acc or di n g t o t he met h o ds i n t he st u d y ma n ual.  T he s yri n ge 

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
c o ntai ni n g G E M 1 0 3 s h o ul d be pre pare d j ust pri or t o t he start of i njecti o n.  It is prefera ble t hat 
t he pre pare d s yri n ge is use d wit hi n 2 h o urs, alt h o u g h it ma y be st ore d at r o o m te m perat ure f or u p 
t o 4 h o urs.  Part of t he pre parati o n ma y i ncl u de dil uti o n. 
F or s u bjects assi g ne d t o t he s ha m + S o C treat me nt gr o u p, a s yri n ge s h o ul d be pre pare d t o ser ve as 
s ha m t o mi mic a real I V T i njecti o n.  F or t he i njecti o n, t he nee dle is re m o ve d a n d o nl y t he h u b of 
t he s yri n ge is hel d t o t he e ye. 
Pri or t o pre parati o n of t he i njecti o n, t he vials of st u d y dr u g s h o ul d be vis uall y i ns pecte d.  T he 
s ol uti o n s h o ul d n ot be use d if it c o ntai ns f orei g n partic ulate matter or is disc ol ore d.  T he c o nte nts 
s h o ul d N O T be war me d usi n g a micr o wa ve or ot her heat s o urce.  G E M 1 0 3 is a pr otei n t hat 
s h o ul d be n ot be s ha ke n a n d s h o ul d be ha n dle d a n d mi xe d ge ntl y t o pre ve nt f oa mi n g. 
Refer t o t he p har mac y ma n ual f or detaile d i nstr ucti o ns re gar di n g t he pre parati o n of t he i njecti o n. 
6. 5. 2  A d mi nistr ati o n of St u d y Dr u g 
All I V T i njecti o ns m ust be a d mi nistere d b y t he I n vesti gat or, or desi g nee ( S u bi n vesti gat or) usi n g 
ase ptic tec h ni q ue c o nsiste nt wit h acce pte d g ui deli nes (e. g., A A O G ui deli nes f or I ntra vitreal 
I njecti o ns 2 0 1 5, R o yal C olle ge of O p ht hal m ol o gists O p ht hal mic Ser vice G ui da nce f or 
I ntra vitreal i njecti o n t hera p y Ma y 2 0 1 8).  St u d y dr u g m ust n ot be i njecte d wit h ot her pr o d ucts i n 
t he sa me s yri n ge, as t he c o m pati bilit y of G E M 1 0 3 i n s ol uti o n wit h ot her pr o d ucts has n ot bee n 
e val uate d.  It is rec o m me n de d t hat all i njecti o ns of G E M 1 0 3 be a d mi nistere d usi n g a 3 0- ga u ge 
nee dle a n d a 1 m L s yri n ge. 
S ha m i njecti o ns will be perf or me d usi n g t he h u b of a 1 m L s yri n ge wit h t he nee dle re m o ve d, t o 
mi mic t he I V T a d mi nistrati o n of st u d y dr u g. 
At eac h d osi n g visit, 2 I V T i njecti o ns ( or s ha m ) will be a d mi nistere d; afli berce pt a n d G E M 1 0 3 
( or s ha m).  T he y will be a d mi nistere d se paratel y t o t he sa me e ye, wit h t he sec o n d i njecti o n 
a d mi nistere d at 9 0°, or 3 cl oc k h o urs dista nce, fr o m t he l ocati o n of t he first i njecti o n.  G E M 1 0 3 
a n d afli berce pt will u n der n o circ u msta nces be a d mi nistere d as 1 c o m bi ne d i njecti o n fr o m t he 
sa me s yri n ge.  T he i ntra vitreal i njecti o ns will be a d mi nistere d i n acc or da nce wit h S o C 
a n d a sterile li d s pec ul u m.  A d mi nister 
afli berce pt ( 2 m g/ 5 0 μ L) first, f oll o we d b y G E M 1 0 3 ( 5 0 0 μ g/ 5 0 μ L) 1 5 mi n utes ( ± 5 mi n utes) 
later.  Meas ure I O P after I V T i njecti o ns as descri be d i n t he S O A (A p pe n di x A ). 
Refer t o t he p har mac y ma n ual f or detaile d i nstr ucti o ns o n t he a d mi nistrati o n of G E M 1 0 3 a n d 
s ha m.  A d mi nister afli berce pt f oll o wi n g t he i nstr ucti o ns i n t he c urre nt, a p pr o ve d f ull prescri bi n g 
i nf or mati o n a n d a n y a vaila ble i nstit uti o nal g ui deli nes, if a p plica ble. 
6. 6  R a n d o miz ati o n of t he St u d y Dr u g 
All s u bjects i n b ot h treat me nt gr o u ps will recei ve E O M treat me nt. 
S u bjects will be ra n d o mize d t o 1 of 2 treat me nts:  G E M 1 0 3 + S o C or s ha m + S o C ( S o C defi ne d as 
afli berce pt E O M) f or a t otal of 6 d oses d uri n g t he 1 2- m o nt h st u d y peri o d. 
P ossi ble c ha n ges t o ra n d o mizati o n a n d s u bse q ue nt a nal ysis base d o n disc o nti n uati o n of 
assi g n me nt t o a st u d y ar m are descri be d i n Secti o n 8. 6 . 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
6. 7  Destr ucti o n of t he St u d y Dr u g 
All st u d y dr u g vials are si n gle- use.  All vials wit h left o ver st u d y dr u g after a d mi nistrati o n will be 
destr o ye d at t he site after acc o u nta bilit y/rec o nciliati o n is c o m plete a n d i n acc or da nce wit h site 
sta n dar d o perati n g pr oc e d ures a n d p olicies g o ver ni n g dr u g destr ucti o n. 
If a n y u n use d st u d y dr u g material is re mai ni n g u p o n c o m pleti o n of t he st u d y, t he material will be 
ret ur ne d t o t he S p o ns or or desi g nee or destr o ye d o nl y after t he S p o ns or or desi g nee has 
perf or me d fi nal dr u g a cc o u nta bilit y/rec o nciliati o n a n d pr o vi de d writte n a ut h orizati o n f or t he 
ret ur n or destr ucti o n of t he st u d y dr u g.  Refer t o t he p har mac y ma n ual f or f urt her i nstr ucti o ns. 

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Pa ge 4 5 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
7  A S S E S S M E N T O F S A F E T Y 
T he met h o ds f or c ollecti n g safet y data are descri be d bel o w.  All pers o n nel i n v ol ve d wit h t he 
st u d y m ust e ns ure t he y are fa miliar wit h t he c o nte nt of t his secti o n. 
7. 1  A Es a n d L a b or at or y A b n or m alities 
7. 1. 1  Cli nic al A Es 
A n A E is a n y u nt o war d me dical occ urre nce i n a s u bject w hic h d oes n ot necessaril y ha ve a ca usal 
relati o ns hi p wit h t he st u d y dr u g.  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 t he st u d y dr u g, w het her or n ot 
c o nsi dere d relate d t o t he me dici nal pr o d uct.  Pre-e xisti n g c o n diti o ns t hat w orse n i n se verit y 
d uri n g t he c o urse of t he st u d y are t o be re p orte d as A Es.  Vital si g ns c o nsi dere d cli nicall y 
si g nifica nt b y t he I n vesti gat or s h o ul d be d oc u me nte d as A Es. 
All A Es (i ncl u di n g pr oce d ure-relate d A Es) occ urri n g d uri n g t he cli nical st u d y f oll o wi n g t he 
si g ni n g of c o nse nt will be re p orte d i n t he A E e C R F. 
T he I n vesti gat or will assess t he se verit y, ca usalit y (relati o ns hi p t o st u d y dr u g), a n d seri o us ness 
of eac h A E. 
Se verit y:  T he I n vesti gat or will assess t he se verit y of all A Es as mil d, m o derate, or se vere base d 
o n t he f oll o wi n g defi niti o ns de vel o pe d fr o m t he Cli nical Data I nterc ha n ge Sta n dar ds C o ns orti u m 
St u d y Data Ta b ulati o n M o del v 3. 1. 1 sta n dar d ter mi n ol o g y. 
 Mil d:   A t y pe of A E t hat is us uall y tra nsie nt a n d ma y re q uire o nl y mi ni mal treat me nt or 
t hera pe utic i nter ve nti o n.  T he e ve nt d oes n ot ge nerall y i nterfere wit h us ual acti vities of 
dail y li vi n g. 
 M o der ate:   A t y pe of A E t hat is us uall y alle viate d wit h a d diti o nal s pecific t hera pe utic 
i nter ve nti o n.  T he e ve nt i nterferes wit h us ual acti vities of dail y li vi n g, ca usi n g 
disc o mf ort, b ut p oses n o si g nifica nt or per ma ne nt ris k of har m t o t he researc h s u bject. 
 Se vere:   A t y pe of A E t hat i nterr u pts us ual acti vities of dail y li vi n g, or si g nifica ntl y 
affects cli nical stat us, or ma y re q uire i nte nsi ve t hera pe utic i nter ve nti o n. 
Ca usalit y:  A Es/ S A Es will be assesse d as n ot relate d, u nli kel y relate d, p ossi bl y relate d, pr o ba bl y 
relate d, or defi nitel y relate d t o st u d y dr u g.  Ta ble 2  pr o vi des ge neral g ui da nce o n t he assess me nt 
of ca usalit y.  F or data re p orti n g p ur p oses, A Es assesse d as n ot relate d or u nli kel y relate d will be 
classifie d as u nrelate d t o st u d y dr u g, a n d A Es assesse d as p ossi bl y relate d, pr o ba bl y relate d, or 
defi nitel y relate d will be classifie d as relate d t o st u d y dr u g.  Assess me nt of ca usalit y s h o ul d be 
base d o n t he I n vesti gat or’s me dical j u d g me nt a n d t he o bser ve d s y m pt o ms ass ociate d wit h t he 
e ve nt. 
E x pecte d ness: A Es/ S A Es will be c o nsi dere d u ne x pecte d if t he e ve nt is n ot liste d i n t he 
I n vesti gat or’s Br oc h ure or is n ot liste d at t he s pecificit y or se verit y t hat has bee n o bser ve d. 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
T a ble 2.  Assess me nt of C a us alit y 
Rel ati o ns hi p t o St u d y Dr u g 
Crite ri a f o r J u d g me nt 
Defi nitel y Rel ate d 
R eas o n a ble te m p oral relati o ns hi p of t h e cli nic al e v e nt t o st u d y dr u g 
a d mi nistrati o n A N D ca n n ot b e reas o n a bl y e x plai n e d b y ot h er fact ors 
(s u c h as t h e s u bject’s cli nical state, c o n c o mita nt t h era p y, a n d/ or ot h er 
i nter v e nti o ns). 
Pr o b a bl y R elate d 
T h e te m p oral relati o ns hi p of t h e cli nical e v e nt t o st u d y dr u g 
a d mi nistrati o n m a k es ca usal r elati o ns hi p pr o ba ble b ut n ot p ossi ble 
A N D ot h er dr u gs, t h era p e utic i nter v e nti o ns, or u n d erl yi n g c o n diti o ns 
d o n ot pr o vi d e a s uffici e nt e x pla n ati o n f or t h e o bser v e d e v e nt. 
P ossi bl y R elate d 
T h e te m p oral relati o ns hi p of t h e cli nical e v e nt t o st u d y dr u g 
a d mi nistrati o n m a k es ca usal r elati o ns hi p p ossi ble b ut n ot u nli k el y 
A N D ot h er dr u gs, t h era p e utic i nter v e nti o ns, or u n d erl yi n g c o n diti o ns 
d o n ot pr o vi d e a s uffici e nt e x pla n ati o n f or t h e o bser v e d e v e nt. 
U nli k el y Relate d 
T h e te m p oral relati o ns hi p of t h e cli nical e v e nt t o st u d y dr u g 
a d mi nistrati o n m a k es ca usal r elati o ns hi p u nli kel y b ut n ot i m p ossi ble 
A N D ot h er dr u gs, t h era p e utic i nter v e nti o ns, or u n d erl yi n g c o n diti o ns 
pr o vi d e a pla usi ble e x pla n ati o n f or t h e o bser v e d e v e nt. 
N ot Relate d 
Data ar e a v ail a ble t o cle arl y i d e ntif y a n alter n ati v e ca us e f or t h e 
rea cti o n. 
Seri o us ness:  A Es will be classifie d as seri o us or n o nseri o us acc or di n g t o t he defi niti o ns 
pr o vi de d bel o w. 
A n S A E is a n y A E t hat is or lea ds t o a n y of t he f oll o wi n g: 
 Deat h 
 I m me diatel y life-t hreate ni n g.  A n A E is c o nsi dere d “life-t hreate ni n g” if, i n t he vie w of 
eit her t he I n vesti gat or or S p o ns or, its occ urre nce places t he s u bject at i m me diate ris k of 
deat h.  It d oes n ot i ncl u de a n A E t hat, ha d it occ urre d i n a m ore se vere f or m, mi g ht ha ve 
ca use d deat h. 
 Re q uires 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 
 C o n ge nital a n o mal y/ birt h defect 
 Persiste nt or si g nifica nt disa bilit y or i nca pacit y 
 A n i m p orta nt me dical e ve nt t hat ma y n ot res ult i n deat h, be life-t hreate ni n g, or re q uire 
h os pitalizati o n ma y be c o nsi dere d a n S A E w he n, base d u p o n a p pr o priate me dical 
j u d g me nt, t he e ve nt ma y je o par dize t he s u bject a n d ma y re q uire me dical or s ur gical 
i nter ve nti o n t o pre ve nt o ne of t he o utc o mes liste d a b o ve 
7. 1. 2  L a b or at or y Test A b n or m alit y 
La b orat or y test res ults eit her will be rec or de d o n t he e C R F or a p pear o n t he la b orat or y re p orts 
s u b mitte d directl y fr o m t he ce ntral la b orat or y.  O ut- of-ra n ge la b orat or y test val ues s h o ul d n ot be 
re p orte d as A Es u nless t he y are c o nsi dere d cli nicall y si g nifica nt a b n or malities b y t he 
I n vesti gat or. 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
7. 2  Rec or di n g of A Es 
At eac h c o ntact wit h t he s u bject, t he I n vesti gat or will elicit i nf or mati o n o n A Es.  A n y 
i nf or mati o n o n A Es s h o ul d be rec or de d i n t he s o urce d oc u me ntati o n a n d i n t he e C R F.  All 
clearl y relate d si g ns, s y m pt o ms, a n d a b n or mal dia g n ostic pr oce d ures res ults s h o ul d be rec or de d 
u n der 1 dia g n osis. 
A n y A Es re mai ni n g u nres ol ve d s h o ul d be rec or de d as “ o n g oi n g.”  O n g oi n g A Es/ S A Es s h o ul d 
c o nti n ue t o be f oll o we d u p f or t he peri o d s pecifie d i n Secti o n 7. 3. 2 .  H o we ver, f oll o w- u p 
i nf or mati o n o n S A Es m ust be re p orte d t o t he S p o ns or or desi g nee as descri be d i n Secti o n 7. 3. 1 .  
A n y S A E t hat occ urs after t he st u d y peri o d a n d is c o nsi dere d t o be relate d or p ossi bl y relate d t o 
t he st u d y treat me nt or st u d y partici pati o n s h o ul d be rec or de d a n d re p orte d i m me diatel y. 
All A Es will be rec or de d b y ti me a n d date.  T he ti me a n d date w he n t he A E starte d a n d st o p pe d, 
t he i nte nsit y, seri o us ness, acti o n ta ke n wit h re gar d t o G E M 1 0 3, ca usalit y assess me nt, a n d 
o utc o me of t he e ve nt will be rec or de d f or eac h A E. 
A Es will be re p orte d f or a mi ni m u m of 3 0 da ys after t he last a d mi nistrati o n of st u d y treat me nt. 
7. 3  Re p orti n g a n d H a n dli n g of S afet y P ar a m eters 
7. 3. 1  S A Es (I m me di atel y Re p ort a ble t o t he S p o ns or) 
All S A Es m ust be re p orte d t o t he S p o ns or or desi g nee i m me diatel y a n d n o later t ha n 2 4 h o urs 
after t he I n vesti gat or’s first k n o wle d ge of t he e ve nt (e x pe dite d re p orti n g).  T o re p ort s uc h e ve nts, 
a n S A E f or m m ust be c o m plete d b y t he I n vesti gat or.  T he I n vesti gat or will kee p a c o p y of t his 
S A E f or m o n file at t he st u d y site. 
T he I n vesti gat or will pr o vi de a n y a d diti o nal i nf or mati o n wit hi n 2 4 h o urs of bec o mi n g a ware of 
t his i nf or mati o n.  T his u p date s h o ul d i ncl u de a c o p y of t he c o m plete d S A E f or m, a n d a n y ot her 
i nf or mati o n t hat will assist wit h t he u n dersta n di n g of t he e ve nt.  Si g nifica nt ne w i nf or mati o n o n 
o n g oi n g S A Es m ust be re p orte d t o t he S p o ns or or desi g nee i m me diatel y a n d n o later t ha n 
2 4 h o urs after t he I n vesti gat or’s bec o mes a ware of t his i nf or mati o n. 
Re p orti n g Seri o us A d verse E ve nts 
 
T he f oll o wi n g c o ntact i nf or mati o n is t o be use d f or S A E re p orti n g:  
 
S y ne os Healt h P har mac o vi gila nce 
T o Re p ort a n S A E se n d t o: safet yre p orti n g @s y ne os healt h.c o m or Fa x t o: 8 7 7- 4 6 4- 7 7 8 7. 
 
T he defi niti o n a n d re p orti n g re q uire me nt are i n acc or da nce wit h I C H G ui deli ne f or Cli nical 
Safet y Data Ma na ge me nt, Defi niti o ns a n d Sta n dar ds f or E x pe dite d Re p orti n g ( T o pic E 2, 1 9 9 5). 
7. 3. 2  A E Re p orti n g Peri o d 
T he st u d y peri o d d uri n g w hic h A Es m ust be re p orte d is defi ne d as t he peri o d fr o m si g nat ure of 
t he i nf or me d c o nse nt t o t he E O S treat me nt f oll o w- u p.  F or t his st u d y, t he st u d y treat me nt f oll o w-
u p is defi ne d as a mi ni m u m of 3 0 da ys after t he last a d mi nistrati o n of st u d y treat me nt.  If t he 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
I n vesti gat or bec o mes a ware of a n S A E t hat is c o nsi dere d t o be relate d t o st u d y treat me nt at a n y 
ti me after t he st u d y, it m ust be re p orte d t o t he S p o ns or. 
7. 3. 3  I n vesti g at or Re p orti n g:  N otif yi n g t he S p o ns or 
S A Es m ust be re p orte d i n acc or da nce wit h t he pr ocess a n d ti meli nes descri be d i n Secti o n 7. 3. 1 . 
7. 3. 4  I n vesti g at or Re p orti n g:  N otif yi n g t he I R B/I E C 
U na ntici pate d pr o ble ms p osi n g ris ks t o s u bjects or ot hers as n ote d a b o ve will be re p orte d t o t he 
I R B/I E C acc or di n g t o l ocal re g ulati o ns.  C o pies of eac h re p ort a n d d oc u me ntati o n of I R B/I E C 
n otificati o n a n d recei pt will be ke pt i n t he I n vesti gat or’s st u d y file. 
7. 3. 5  S p o ns or Re p orti n g:  N otif yi n g Re g ul at o r y A ut h orities 
T he S p o ns or is re q uire d t o re p ort certai n st u d y e ve nts i n a n e x pe dite d ma n ner t o t he F D A.  T he 
f oll o wi n g descri bes t he safet y re p orti n g re q uire me nts b y ti meli ne f or re p orti n g a n d ass ociate d 
t y pe of e ve nt: 
 I m me diatel y a n d wit hi n 7 cale n dar da ys 
o  A n y s us pecte d a d verse reacti o n t hat is:  ass ociate d wit h t he use of t he st u d y dr u g, 
u ne x pecte d, a n d fatal or life-t hreate ni n g 
o  F oll o w- u p i nf or mati o n m ust be re p orte d i n t he f oll o wi n g 8 cale n dar da ys 
 I m me diatel y a n d wit hi n 1 5 cale n dar da ys  
o  A n y s us pecte d a d verse reacti o n t hat is:  ass ociate d wit h t he use of t he st u d y dr u g, 
u ne x pecte d, a n d seri o us, b ut n ot fatal or life-t hreate ni n g 
o  A n y fi n di n g fr o m tests i n la b orat or y a ni mals t hat s u g gest a si g nifica nt ris k f or 
h u ma n s u bjects i ncl u di n g re p orts of m uta ge nicit y, terat o ge nicit y, or 
carci n o ge nicit y 
o  A n y e ve nt i n c o n necti o n wit h t he c o n d uct of t he st u d y or t he de vel o p me nt of t he 
i n vesti gati o nal me dici nal pr o d uct t hat ma y affect t he safet y of t he st u d y s u bjects 
o  F oll o w- u p i nf or mati o n m ust be re p orte d wit hi n 1 5 cale n dar da ys 
F or t he p ur p oses of e x pe dite d re p orti n g, t he deter mi nati o n of ca usalit y will be t he res p o nsi bilit y 
of t he S p o ns or wit h c o nsi derati o n of t he I n vesti gat or's assess me nt of ca usalit y. 
T he S p o ns or will c o m pl y wit h all a d diti o nal l ocal safet y re p orti n g re q uire me nts, as a p plica ble. 
7. 3. 6  S p o ns or Re p orti n g:  N otif yi n g P artici p ati n g I n vesti g at ors 
It is t he res p o nsi bilit y of t he S p o ns or or desi g nee t o i m me diatel y n otif y all partici pati n g 
I n vesti gat ors of a n y A E ass ociate d wit h t he use of t he dr u g t hat is b ot h seri o us a n d u ne x pecte d, 
as well as a n y fi n di n g fr o m tests i n la b orat or y a ni mals t hat s u g gest a si g nifica nt ris k f or h u ma n 
s u bjects. 
7. 3. 7  Tre at me nt a n d F oll o w- u p of A Es 
D uri n g t he st u d y, all S A Es a n d oc ular A Es will be f oll o we d u p u ntil t he y ha ve ret ur ne d t o 
baseli ne stat us or sta bilize d or u ntil t he I n vesti gat or a n d S p o ns or a gree t hat f oll o w- u p is n o 
l o n ger necessar y.  If a clear e x pla nati o n is esta blis he d, it s h o ul d be d oc u me nte d. 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
Treat me nt of A Es is at t he discreti o n of t he I n vesti gat or a n d s h o ul d f oll o w t he sta n dar ds of 
me dical care at t he I n vesti gat or’s i nstit uti o n. 
7. 3. 8  F oll o w- u p of A b n or m al L a b or at or y Test V al ues 
I n t he e ve nt of u ne x plai ne d cli nicall y si g nifica nt a b n or mal la b orat or y val ues, t he tests s h o ul d be 
re peate d i m me diatel y a n d f oll o we d u p u ntil t he y ha ve ret ur ne d t o baseli ne val ues a n d/ or a n 
a de q uate e x pla nati o n of t he a b n or malit y is f o u n d.  If a clear e x pla nati o n is esta blis he d, it s h o ul d 
be rec or de d; t his f oll o w- u p ma y occ ur wit h t he s u bject’s pri mar y care p h ysicia n. 
7. 3. 9  Pre g n a nc y 
C o ntrace pti o n a n d pre g na nc y a v oi da nce pr oce d ures are descri be d i n Secti o n 4. 5. 2 . 
A fe male s u bject m ust be a d vise d t o i m me diatel y i nf or m t he I n vesti gat or if s he bec o mes 
pre g na nt d uri n g t he st u d y a n d m ust n ot recei ve f urt her G E M 1 0 3 i njecti o ns.  Pre g na ncies 
occ urri n g t hr o u g h t he E O S m ust be re p orte d t o t he I n vesti gat or.  T he I n vesti gat or m ust re p ort all 
pre g na ncies t o t he S p o ns or wit hi n 2 4 h o urs of n otificati o n.  T he I n vesti gat or s h o ul d c o u nsel t he 
s u bject disc ussi n g t he ris ks of c o nti n ui n g wit h t he pre g na nc y a n d t he p ossi ble effects o n t he 
fet us.  M o nit ori n g of t he s u bject s h o ul d c o nti n ue u ntil c o ncl usi o n of t he pre g na nc y. 
Pre g na nc y occ urri n g i n t he part ner of a s u bject partici pati n g i n t he st u d y (t hr o u g h t he E O S) m ust 
als o be re p orte d t o t he I n vesti gat or a n d t he S p o ns or.  T he part ner s h o ul d be c o u nsele d a n d 
f oll o we d as descri be d a b o ve (Secti o n 4. 5. 2 ). 
7. 4  Me dic al Re vie w C o m mittee ( M R C) 
A n M R C c o nsisti n g of S p o ns or me dical pers o n nel a n d i n de pe n de nt me dical e x pert(s) will meet 
a p pr o xi matel y q uarterl y t o re vie w safet y i nf or mati o n f or t he st u d y.  T he first meeti n g is pla n ne d 
t o occ ur after at least 3 s u bjects ha ve c o m plete d 3 d oses of G E M 1 0 3 + S o C.  T he M R C ma y als o 
be c o n ve ne d f or a n a d h oc meeti n g t o disc uss i nteri m safet y fi n di n gs at t he discreti o n of t he 
S p o ns or (e. g., if 2 or m ore s u bjects re p ort cli nicall y si milar st u d y dr u g-relate d S A Es). 

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
8  S T A TI S TI C A L P L A N 
8. 1   Ge ner al C o nsi der ati o ns 
Descri pti ve s u m mar y statistics will be pr o vi de d f or de m o gra p hics, dis p ositi o n, a n d d ose 
e x p os ure.  T he n u m ber a n d perce nta ge of s u bjects w h o disc o nti n ue d fr o m t he st u d y, al o n g wit h 
reas o ns f or disc o nti n uati o ns, will be ta b ulate d a n d descri be d i n listi n gs.  All descri pti ve 
s u m maries will be pr o vi de d b y treat me nt gr o u p ( G E M 1 0 3 vs s ha m). 
C o nti n u o us data will be s u m marize d usi n g descri pti ve statistics ( n u m ber of s u bjects, mea n, 
sta n dar d de viati o n, me dia n, mi ni m u m, a n d ma xi m u m) a n d, w here a p pr o priate, gra p hic 
re prese ntati o n, a n d t w o-
s u m marize d b y sa m ple size, pr o p orti o ns, a n d t w o-
 
A n y re p orte d p- val ues will be c o nsi dere d part of t he descri pti ve a nal yses (i.e., h y p ot hesis-
ge nerati n g) a n d will n ot be a dj uste d f or m ulti plicit y.  T he p hrase “statisticall y si g nifica nt” ma y 
be use d i nterc ha n gea bl y wit h “ n o mi nall y statisticall y si g nifica nt” t o i n dicate t hat a n o mi nal 
p-
 
F ull a nal ysis details will be pr o vi de d i n a se parate Statistical A nal ysis Pla n ( S A P). 
8. 2  Deter mi n ati o n of S a m ple Size 
T he pla n ne d t otal sa m ple size of a p pr o xi matel y 4 5 s u bjects ( ~ 3 0 treate d wit h G E M 1 0 3 + S o C, 
~ 1 5 treate d wit h s ha m + S o C; S o C defi ne d as afli berce pt E O M) is base d o n feasi bilit y 
c o nsi derati o ns, rat her t ha n a n y s pe cific statistical test. 
8. 3  A n al ysis Sets 
8. 3. 1  C o nse nte d S u bject Set 
T he C o nse nte d S u bject Set will i ncl u de s u bjects w h o si g ne d t he I C F a n d will be use d t o create a 
dia gra m t o ill ustrate s u bject fl o w fr o m c o nse nt t hr o u g h dis p ositi o n (si milar t o a C o ns oli date d 
Sta n dar ds of Re p orti n g Trials [ C O N S O R T] dia gra m f or a ra n d o mize d trial). 
8. 3. 2  Bi o m ar ker Set 
T he Bi o mar ker Set will i ncl u de s u bjects wit h s ufficie nt data t o assess bi o mar ker res ults. 
8. 3. 3  F ull A n al ysis Set 
T he F ull A nal ysis Set ( F A S) will i ncl u de all s u bjects w h o recei ve at least 1 d ose of st u d y dr u g 
( G E M 1 0 3 or s ha m).  Safet y a nal yses will be perf or me d o n t he F A S.  A nal yses o n t he F A S are 
c o nsiste nt wit h t he i nte nti o n-t o-treat pri nci ple. 
8. 4  De m o gr a p hics a n d S afet y A n al ysis 
De m o gra p hic baseli ne c haracteristic data will be s u m marize d acc or di n g t o t he met h o ds 
descri be d i n Secti o n 8. 1 . 
Vari o us a nal yses t o descri be s u bject c haracteristics will be perf or me d s uc h as le n gt h of pri or 
afli berce pt treat me nt, t y pe of C N V lesi o ns, etc. 
Descri pti ve statistics will be c o m p ute d f or safet y para meters, as a p pr o priate.  N u m ber a n d 
perce nta ge of s u bjects w h o disc o nti n ue d fr o m t he st u d y beca use of A Es will be ta b ulate d acr oss 
d ose c o h orts; se verit y a n d fre q ue nc y of A Es a n d S A Es will als o be ta b ulate d acr oss treat me nt 

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
gr o u ps.  All ot her safet y data will be pr o vi de d i n listi n gs.  P h ysical e xa mi nati o n fi n di n gs, cli nical 
la b orat or y val ues, a n d vital si g ns will be s u m marize d b y d ose c o h ort. 
T he pr o p orti o n of s u bjects wit h meas ura ble a nti b o dies t o G E M 1 0 3 will be dis pla ye d. 
F urt her statistical e val uati o ns will be a p plie d f or select e n d p oi nts, if warra nte d.  All baseli ne data 
a n d safet y data c ollecte d d uri n g t he st u d y will be liste d f or eac h s u bject. 
All A Es will be c o de d usi n g a c o nsiste nt versi o n of t he Me dical Dicti o nar y f or Re g ulat or y 
Acti vities ( Me d D R A, versi o n 2 2. 0 or hi g her) a n d will be classifie d b y Me d D R A s yste m or ga n 
class ( S O C) a n d preferre d ter m ( P T). 
A E a nal yses will i ncl u de t he f oll o wi n g ta b ular s u m maries: 
 S u m mar y of all A Es 
 I nci de nce of A Es b y S O C a n d P T 
 I nci de nce of A Es b y se verit y 
 I nci de nce of S A Es 
 I nci de nce of treat me nt-relate d A Es 
8. 5  Bi o m ar ker, I m a gi n g, a n d Cli nic al E n d p oi nt A n al ysis 
A q ue o us h u m or will be c ollecte d pri or t o t he first d ose, a n d j ust pri or t o eac h G E M 1 0 3/s ha m 
I V T i njecti o n t o e val uate c o m ple me nt pr otei ns a n d p ossi bl y i nfla m mat or y c yt o ki ne pr ofiles t o 
deter mi ne t heir p ote ntial as P D bi o mar kers f or usef ul ness i n a pi v otal st u d y.  T otal C F H 
c o nce ntrati o ns i n a q ue o us h u m or a n d plas ma will be e val uate d. 
I ma gi n g e n d p oi nts s uc h as C N V lesi o n size, M A lesi o n size, reti nal la yer t hic k ness or prese nce 
of fl ui d, a n d cli nical e n d p oi nts s uc h as B C V A, l o w l u mi na nce vis ual ac uit y ( L L V A), a n d l o w 
l u mi na nce deficit, will be a nal yze d acc or di n g t o t he met h o ds of Secti o n 8. 1 . 
A nal yses of bi o mar kers, i ma gi n g assess me nts, a n d cli nical e n d p oi nts will be descri pti ve, a n d 
will s u m marize act ual val ues a n d c ha n ges fr o m baseli ne o ver ti me.  Gra p hical dis pla ys will als o 
be create d. 
A nal ysis of bi o mar ker, i ma gi n g, a n d cli nical e n d p oi nt c ha n ges fr o m baseli ne will pri maril y 
e m pl o y t he Wilc o x o n ra n k-s u m test. 
F ull a nal ysis details will be pr o vi de d i n t he S A P. 
8. 6  S u m m aries of D at a Pri or t o St u d y C o m pleti o n 
I nteri m data ma y be s u m marize d f or prese ntati o n t o re g ulat or y a ut h orities or t o t he scie ntific 
c o m m u nit y t o facilitate disc ussi o ns a n d o btai n i n p ut o n late p hase st u d y desi g ns. 
As t he desi g n of t his st u d y is n ot base d o n a s pecific statistical test, n o a dj ust me nts will be ma de 
t o t he fi nal a nal yses f or t his t y pe of c ha n ge, b ut t he c ha n ge itself will be n ote d i n t he fi nal 
cli nical st u d y re p ort ( C S R), a n d se nsiti vit y a nal yses will be perf or me d t o assess p ote ntial i m pact 
of t he c ha n ge. 
F or s o me of t hese s u m maries, CIs ma y be c o m p ute d.  A d diti o nal details of t he pres pecifie d 
statistical a nal yses will be pr o vi de d i n t he S A P. 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
8. 6. 1  H a n dli n g of Missi n g D at a 
I n ge neral, missi n g res ults will n ot be i m p ute d.  A d diti o nal i nf or mati o n, i ncl u di n g i nf or mati o n 
a b o ut missi n g data relate d t o C O VI D- 1 9, ca n be f o u n d i n t he S A P. 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
9  D A T A Q U A LI T Y A N D A S S U R A N C E, S U B J E C T 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 
All as pects of t he st u d y will be m o nit ore d f or c o m plia nce wit h a p plica ble g o ver n me nt 
re g ulati o ns wit h res pect t o c urre nt I C H har m o nise d tri partite g ui deli ne E 6( R 2):  G C P a n d c urre nt 
sta n dar d o perati n g pr oce d ures.  A n electr o nic data ca pt ure s yste m t hat is vali date d a n d c o m plia nt 
wit h U S Title 2 1 of t he C F R Part 1 1 will be use d. 
I nf or mati o n a b o ut st u d y s u bjects will be ke pt c o nfi de ntial a n d ma na ge d acc or di n g t o t he 
re q uire me nts of a p plica ble l ocal re g ulati o ns.  F urt her details are descri be d i n Secti o n 1 1. 1 . 
9. 1  S o urce D oc u m e nts 
S o urce data is all i nf or mati o n, ori gi nal rec or ds of cli nical fi n di n gs, o bser vati o ns, or ot her 
acti vities i n a cli nical st u d y necessar y f or t he rec o nstr ucti o n a n d e val uati o n of t he st u d y.  S o urce 
data are c o ntai ne d i n s o urce d oc u me nts.  E xa m ples of t hese ori gi nal d oc u me nts a n d data rec or ds 
i ncl u de:  h os pital rec or ds, cli nical a n d office c harts, la b orat or y n otes, me m ora n da, s u bjects’ 
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-ra ys, s u bject 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. 
T he i ma ges pl us a u xiliar y i nf or mati o n will be st ore d l ocall y b ut als o tra ns mitte d t o t he S p o ns or 
i n Di gital I ma gi n g a n d C o m m u nicati o ns i n Me dici ne f or mat f or p ote ntial f urt her i nter nal 
a nal yses a n d f or ge nerati o n of ill ustrati ve i ma ges. 
9. 2  C ase Re p ort F or ms ( C R Fs) 
Re q uire d data f or t his st u d y will be ca pt ure d o n C R Fs via electr o nic data ca pt ure (e C R Fs) u nless 
ot her wise s pecifie d i n t his d oc u me nt.  E xce pt f or data p oi nts f or w hic h t he pr ot oc ol i n dicates t hat 
t he e C R F ma y ser ve as s o urce d oc u me ntati o n, data are t o be o btai ne d fr o m t he s u bject’s s o urce 
d oc u me nts a n d t he n e ntere d i nt o t he e C R F b y a ut h orize d pers o n nel.  Cli nical data t hat are n ot 
rec or de d o n t he e C R F will be ca pt ure d a n d tra nsferre d t o t he S p o ns or or its desi g nee. 
9. 3  Rec or ds Rete nti o n 
It is t he I n vesti gat or’s res p o nsi bilit y t o retai n st u d y esse ntial d oc u me nts 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 f or G E M 1 0 3 i n t heir c o u ntr y a n d u ntil 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 heir c o u ntr y or at least 2 years 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 G E M 1 0 3.  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 b y t he l ocal le gislati o n re q uire me nts or a n a gree me nt 
wit h t he S p o ns or.  I n s uc h a n i nsta nce, it is t he res p o nsi bilit y of t he S p o ns or t o i nf or m t he 
I n vesti gat or/i nstit uti o n as t o w he n t hese d oc u me nts n o l o n ger nee d t o be retai ne d. 

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D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
1 0  S T U D Y M O NI T O RI N G, A U DI TI N G, A N D I N S P E C TI N G 
1 0. 1  St u d y M o nit ori n g Pl a n 
T his st u d y will be m o nit ore d acc or di n g t o t he st u d y m o nit ori n g pla n.  T he I n vesti gat or will 
all ocate a de q uate ti me f or s uc h m o nit ori n g acti vities.  T he I n vesti gat or will als o e ns ure t hat t he 
m o nit or or ot her c o m plia nce or q ualit y ass ura nce re vie wer is gi ve n access t o all t he a b o ve n ote d 
st u d y-relate d d oc u me nts a n d st u d y-relate d facilities (e. g., dia g n ostic la b orat or y), a n d has 
a de q uate s pace t o c o n d uct t he m o nit ori n g visit. 
T he cli nical m o nit or, as a re prese ntati ve of t he S p o ns or, is o bli gate d t o f oll o w t he st u d y cl osel y.  
I n d oi n g s o, t he m o nit or will visit t he I n vesti gat or a n d st u d y facilit y at peri o dic i nter vals, i n 
a d diti o n t o mai ntai ni n g necessar y tele p h o ne a n d letter c o ntact.  T he m o nit or will mai ntai n 
c urre nt pers o nal k n o wle d ge of t he st u d y t hr o u g h o bser vati o n, re vie w of st u d y rec or ds a n d s o urce 
d oc u me ntati o n, a n d disc ussi o n of t he c o n d uct of t he st u d y wit h t he I n vesti gat or a n d staff. 
All as pects of t he st u d y will be caref ull y m o nit ore d b y t he S p o ns or or its desi g nee f or 
c o m plia nce wit h a p plica ble g o ver n me nt re g ulati o n wit h res pect t o c urre nt I C H E 6( R 2) 
g ui deli nes a n d sta n dar d o perati n g pr oce d ures. 
1 0. 2  A u diti n g a n d I ns pecti n g 
T he I n vesti gat or will per mit st u d y-relate d m o nit ori n g, a u dits, a n d i ns pecti o ns b y t he I R B/I E C, 
t he S p o ns or ( or t heir desi g nee), g o ver n me nt re g ulat or y b o dies, a n d q ualit y ass ura nce gr o u ps of 
all st u d y-relate d d oc u me nts (e. g., s o urce d oc u me nts, re g ulat or y d oc u me nts, data c ollecti o n 
i nstr u me nts, st u d y data).  I n t he e ve nt of a n a u dit, t he I n vesti gat or a grees t o all o w t he S p o ns or, 
t heir re prese ntati ves, t he F D A, t he De part me nt of Defe nse or fe deral re prese ntati ves, or ot her 
re g ulat or y a ge ncies access t o all st u d y rec or ds.  T he I n vesti gat or will e n s ure t he ca pa bilit y f or 
i ns pecti o ns of a p plica ble st u d y-relate d facilities (e. g., dia g n ostic la b orat or y). 
T he I n vesti gat or s h o ul d pr o m ptl y n otif y t he S p o ns or of a n y a u dits sc he d ule d b y a n y re g ulat or y 
a ut h orities a n d pr o m ptl y f or war d c o pies of a n y a u dit re p orts recei ve d t o t he S p o ns or. 
1 0. 3  M a n a ge m e nt of Pr ot oc ol A m e n d m e nts a n d De vi ati o ns 
1 0. 3. 1  M o dific ati o n of t he Pr ot oc ol 
A n y c ha n ges i n t his researc h acti vit y, e xce pt t h ose necessar y t o re m o ve a n a p pare nt, i m me diate 
hazar d t o t he s u bject, 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 or desi g nee.  A me n d me nts 
t o t he pr ot oc ol m ust be s u b mitte d i n writi n g t o t he I n vesti gat or’s I R B f or a p pr o val bef ore 
s u bjects are e nr olle d i nt o a n a me n de d pr ot oc ol. 
1 0. 3. 2  Pr ot oc ol De vi ati o ns 
T he I n vesti gat or or desi g nee m ust d oc u me nt a n d e x plai n i n t he s u bject’s s o urce d oc u me ntati o n 
a n y de viati o n fr o m t he a p pr o ve d pr ot oc ol.  T he I n vesti gat or ma y i m ple me nt a de viati o n fr o m, or 
a c ha n ge t o, t he pr ot oc ol t o eli mi nate a n i m me diate hazar d t o st u d y s u bjects wit h o ut pri or I R B 
a p pr o val.  As s o o n as p ossi ble after s uc h a n occ urre nce, t he i m ple me nte d de viati o n or c ha n ge, 
t he reas o ns f or it, a n d a n y pr o p ose d pr ot oc ol a me n d me nts s h o ul d be s u b mitte d t o t he I R B f or 
re vie w a n d a p pr o val, t o t he S p o ns or f or a gree me nt, a n d t o t he re g ulat or y a ut h orities, if re q uire d. 
A st u d y de viati o n is a si g nifica nt or a n o nsi g nifica nt de viati o n fr o m t he pr ot oc ol or t o I C H G C P 
E 6 R 2 or a n o nc o m plia nce wit h a p plica ble re g ulat or y re q uire me nts.  N o nsi g nifica nt pr ot oc ol 
de viati o ns d o n ot i m pact t he e n d p oi nts or t he safet y or me ntal i nte grit y of a s u bject or t he 

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G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
scie ntific val ue of t he st u d y.  A pr ot oc ol vi olati o n or si g nifica nt de viati o n occ urs w he n t he 
s u bject or I n vesti gat or di d n ot a d here t o t he pr ot oc ol, a n d t he de viati o n affects pri mar y efficac y 
a n d safet y assess me nts, t he safet y or me ntal i nte grit y of a s u bject, or t he scie ntific val ue of t he 
st u d y. 
All de viati o ns, si g nifica nt a n d n o nsi g nifica nt, will be re vie we d a n d d oc u me nte d b y t he cli nical 
tea m t hr o u g h o ut t he c o urse of t he st u d y.  T he I n vesti gat or will be n otifie d i n writi n g b y t he 
m o nit or of all de viati o ns.  T he I R B s h o ul d be n otifie d of all pr ot oc ol de viati o ns, if a p pr o priate, 
i n a ti mel y ma n ner.  T he cli nical tea m will f oll o w all de viati o ns u ntil res ol ve d. 
1 0. 4  St u d y Ter mi n ati o n 
T he S p o ns or reser ves t he ri g ht t o disc o nti n ue t he st u d y at a n y ti me f or cli nical or a d mi nistrati ve 
reas o ns. 
T he E O S is defi ne d as t he date o n w hic h t he last s u bject c o m pletes t he last visit (i ncl u des t he 
E O S visit a n d a n y a d diti o nal l o n g-ter m f oll o w- u p).  A n y a d diti o nal l o n g-ter m f oll o w- u p t hat is 
re q uire d t o m o nit or t he res ol uti o n of a fi n di n g or A E ma y be re p orte d t hr o u g h a n a me n d me nt t o 
t he C S R. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 5 6 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
1 1  I N V E S TI G A T O R O B LI G A TI O N S 
T he f oll o wi n g a d mi nistrati ve ite ms are mea nt t o g ui de t he I n vesti gat or i n t he c o n d uct of t he 
st u d y a n d ma y be s u bject t o c ha n ge base d o n i n d ustr y a n d g o ver n me nt sta n dar d o perati n g 
pr oce d ures, w or ki n g practice d oc u me nts, or g ui deli nes.  C ha n ges will be re p orte d t o t he I R B b ut 
will n ot res ult i n pr ot oc ol a me n d me nts. 
1 1. 1  C o nfi de nti alit y 
I nf or mati o n a b o ut st u d y s u bjects will be ke pt c o nfi de ntial a n d ma na ge d acc or di n g t o t he 
re q uire me nts of a p plica ble l ocal re g ulati o ns. 
All la b orat or y s peci me ns, e val uati o n f or ms, re p orts, a n d ot her rec or ds will be i de ntifie d i n a 
ma n ner desi g ne d t o mai ntai n s u bject c o nfi de ntialit y.  All rec or ds will be ke pt i n a sec ure st ora ge 
area wit h li mite d access.  Cli nical i nf or mati o n will n ot be release d wit h o ut t he writte n 
per missi o n of t he s u bject (t hr o u g h t he I C F), e xce pt as necessar y f or m o nit ori n g, a u diti n g, a n d 
a nal yses b y t he S p o ns or, its desi g nee, rele va nt re g ulat or y a ut h orit y, or t he I R B. 
T he I n vesti gat or a n d all e m pl o yees a n d c o w or kers i n v ol ve d wit h t his st u d y ma y n ot discl ose or 
use f or a n y p ur p ose ot her t ha n perf or ma nce of t he st u d y a n d f ut ure researc h, a n y data, rec or d, or 
ot her u n p u blis he d, c o nfi de ntial i nf or mati o n discl ose d t o t h ose i n di vi d uals f or t he p ur p ose of t he 
st u d y.  Pri or writte n a gree me nt fr o m t he S p o ns or or its desi g nee m ust be o btai ne d f or t he 
discl os ure of a n y sai d c o nfi de ntial i nf or mati o n t o ot her parties. 
1 1. 2  I nstit uti o n al Re vie w 
Fe deral re g ulati o ns a n d t he I C H E 6( R 2) g ui deli nes re q uire t hat a p pr o val be o btai ne d fr o m a n 
I R B bef ore partici pati o n of h u ma n s u bjects i n researc h st u dies.  Bef ore st u d y o nset, t he pr ot oc ol, 
I C F, a d vertise me nts t o be use d f or t he recr uit me nt of st u d y s u bjects, a n d a n y ot her writte n 
i nf or mati o n re gar di n g t his st u d y t o be pr o vi de d t o t he s u bject m ust be a p pr o ve d b y t he I R B.  
D oc u me ntati o n of all I R B a p pr o vals a n d of t he I R B c o m plia nce wit h t he I C H E 6( R 2) g ui deli nes 
will be mai ntai ne d b y t he site a n d will be a vaila ble f or re vie w b y t he S p o ns or or its desi g nee. 
1 1. 3  S u bject C o nse nt 
T he I n vesti gat or is re q uire d t o o btai n i nf or me d c o nse nt acc or di n g t o Secti o n 5. 1. 1  of t his 
pr ot oc ol a n d a p pr o priate l ocal re q uire me nts a n d re g ulati o ns pri or t o e nr olli n g a s u bject i n t his 
st u d y. 
1 1. 4  Fi n a nci al Discl os ure a n d O bli g ati o ns 
T he I n vesti gat or is re q uire d t o pr o vi de fi na ncial discl os ure i nf or mati o n t o all o w t he S p o ns or t o 
s u b mit t he c o m plete a n d acc urate certificati o n or discl os ure state me nts re q uire d u n der 
2 1 C F R 5 4.  I n a d diti o n, t he I n vesti gat or m ust pr o vi de t o t he S p o ns or a c o m mit me nt t o pr o m ptl y 
u p date t his i nf or mati o n if a n y rele va nt c ha n ges occ ur d uri n g t he c o urse of t he i n vesti gati o n a n d 
f or 1 year after t he c o m pleti o n of t he st u d y. 
Neit her t he S p o ns or, its dele gates, n or t he st u d y site is fi na nciall y res p o nsi ble f or f urt her testi n g 
or treat me nt of a n y me dical c o n diti o n t hat ma y be detecte d d uri n g t he scree ni n g pr ocess.  I n 
a d diti o n, i n t he a bse nce of s pecific arra n ge me nts, neit her t he S p o ns or, its ve n d ors, n or t he st u d y 
site is fi na nciall y res p o nsi ble f or f urt her treat me nt of t he disease u n der st u d y. 

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5 Ma y 2 0 2 1 
Pa ge 5 7 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
1 1. 5  St u d y C o n d uct a n d A d here nce t o Pr ot oc ol 
T he I n vesti gat or a grees t hat t he st u d y will be c o n d ucte d acc or di n g t o t he pri nci ples of 
I C H E 6( R 2).  T he I n vesti gat or will c o n d uct all as pects of t his st u d y i n acc or da nce wit h all 
nati o nal, state, a n d l ocal la ws or re g ulati o ns.  T he st u d y will be c o n d ucte d i n c o m plia nce wit h 
t he pr ot oc ol, c urre nt G C P g ui deli nes – a d o pti n g t he pri nci ples of t he Declarati o n of Helsi n ki – 
a n d all a p plica ble re g ulat or y re q uire me nts. 
1 1. 6  D at a C ollecti o n 
As part of t he res p o nsi bilities ass u me d b y partici pati n g i n t he st u d y, t he I n vesti gat or a grees t o 
mai ntai n a de q uate case hist ories f or s u bjects treate d as part of t he researc h u n der t his pr ot oc ol.  
T he I n vesti gat or a grees t o mai ntai n acc urate e C R Fs a n d s o urce d oc u me ntati o n as part of t he case 
hist ories.  T hese s o urce d oc u me nts ma y i ncl u de la b orat or y re p orts a n d si milar s o urces. 
Electr o nic C R Fs are accesse d t hr o u g h a n electr o nic data ca pt ure s yste m t hat is vali date d a n d 
c o m plia nt wit h 2 1 C F R 1 1. 
1 1. 7  Re p orti n g A d verse E ve nts 
B y partici pati n g i n t his st u d y, t he I n vesti gat or a grees t o s u b mit re p orts of S A Es acc or di n g t o t he 
ti meli ne a n d met h o ds o utli ne d i n t his pr ot oc ol (f or details refer t o Secti o n 7 ).  I n a d diti o n, t he 
I n vesti gat or a grees t o s u b mit a n n ual re p orts t o his I R B as a p pr o priate.  T he I n vesti gat or als o 
a grees t o pr o vi de t he S p o ns or wit h a n a de q uate re p ort, if a p plica ble, s h ortl y after c o m pleti o n of 
t he I n vesti gat or’s partici pati o n i n t he st u d y. 
1 1. 8  Rec or ds Rete nti o n 
Esse ntial d oc u me nts s h o ul d be retai ne d u ntil 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 a n I C H re gi o n a n d u ntil 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 a n I C H re gi o n or at least 2 years 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 st u d y dr u g.  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, 
h o we ver, if re q uire d b y t he a p plica ble re g ulat or y re q uire me nts or b y a n a gree me nt wit h t he 
S p o ns or.  It is t he S p o ns or’s res p o nsi bilit y t o i nf or m t he I n vesti gat or/i nstit uti o n as t o w he n t hese 
d oc u me nts n o l o n ger nee d t o be retai ne d. 
1 1. 9  P u blic ati o ns 
After c o m pleti o n of t he st u d y, t he data ma y be c o nsi dere d f or re p orti n g at a scie ntific meeti n g or 
f or p u blicati o n i n a scie ntific j o ur nal.  I n t hese cases, t he S p o ns or will be res p o nsi ble f or t hese 
acti vities a n d will w or k wit h t he I n vesti gat ors t o deter mi ne h o w t he ma n uscri pt is writte n a n d 
e dite d, t he n u m ber a n d or der of a ut h ors, t he p u blicati o n t o w hic h it will be s u b mitte d, a n d ot her 
relate d iss ues.  T he S p o ns or has fi nal a p pr o val a ut h orit y o ver decisi o ns relate d t o data 
p u blicati o n. 
Data are t he pr o pert y of t he S p o ns or a n d ca n n ot be p u blis he d wit h o ut t heir pri or a ut h orizati o n. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 5 8 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
1 2  E T HI C A L C O N SI D E R A TI O N S 
T his st u d y is t o be c o n d ucte d i n acc or da nce wit h i nter nati o nal sta n dar ds of G C P (I C H, E U 
Directi ves 2 0 0 1/ 2 0/ E C a n d 2 0 0 5/ 2 8/ E C, a n d U S 2 1 C F R 5 0 a n d 2 1 C F R 3 1 2), as well as all ot her 
a p plica ble g o ver n me nt re g ulati o ns a n d i nstit uti o nal researc h p olicies a n d pr oce d ures. 
T his pr ot oc ol a n d a n y a me n d me nts will be s u b mitte d t o a pr o perl y c o nstit ute d I R B/I E C, i n 
a gree me nt wit h l ocal le gal re q uire me nts, f or f or mal a p pr o val of t he st u d y c o n d uct.  T he decisi o n 
of t he I R B/I E C c o ncer ni n g t he c o n d uct of t he st u d y will be ma de i n writi n g t o t he a p plica nt a n d 
a c o p y of t his decisi o n will be pr o vi de d t o t he S p o ns or bef ore c o m me nce me nt of t his st u d y.  T he 
I R B/I E C will be re q ueste d t o pr o vi de a list of I R B/I E C me m bers.  A me m ber w h o is affiliate d 
wit h t he S p o ns or s h o ul d n ot partici pate i n v oti n g o n t he I R B/I E C o pi ni o n. 
Eac h s u bject will be gi ve n a n I C F descri bi n g t his st u d y a n d pr o vi di n g s ufficie nt i nf or mati o n t o 
all o w t he s u bject t o ma ke a n i nf or me d decisi o n a b o ut t he s u bject’s partici pati o n i n t his st u d y.  
T his I C F will be s u b mitte d wit h t he pr ot oc ol f or re vie w a n d a p pr o val b y t he I R B/I E C f or t he 
st u d y.  T he f or mal c o nse nt of a s u bject, usi n g t he I R B/I E C-a p pr o ve d I C F, m ust be o btai ne d 
bef ore t hat s u bject u n der g oes a n y st u d y pr oce d ure.  T he I C F m ust be si g ne d b y t he s u bject, a n d 
t he I n vesti gat or- desi g nate d researc h pr ofessi o nal o btai ni n g t he c o nse nt. 
A n y c ha n ges i n t he st u d y pr ot oc ol, s uc h as c ha n ges i n t he st u d y desi g n, o bjecti ves or e n d p oi nts, 
i ncl usi o n a n d e xcl usi o n criteria, a n d/ or pr oce d ures (e xce pt t o eli mi nate a n i m me diate hazar d) 
will be i m ple me nte d o nl y after t he m ut ual a gree me nt of t he I n vesti gat or a n d t he S p o ns or or 
desi g nee.  All pr ot oc ol c ha n ges m ust be d oc u me nte d i n pr ot oc ol a me n d me nt(s).  Pr ot oc ol 
a me n d me nt(s) m ust be si g ne d b y t he I n vesti gat or a n d a p pr o ve d (if a p plica ble) b y t he I R B/I E C 
pri or t o i m ple me ntati o n.  A n y c ha n ges i n st u d y c o n d uct t hat res ult fr o m a pe n di n g a me n d me nt 
will be c o nsi dere d pr ot oc ol de viati o ns u ntil I R B/I E C a p pr o val is gra nte d.  D oc u me ntati o n of 
I R B/I E C a p pr o val m ust be ret ur ne d t o t he S p o ns or or desi g nee.  U p o n c o m pleti o n of t he st u d y, 
t he I n vesti gat or, w here a p plica ble, s h o ul d i nf or m t he i nstit uti o n; t he I n vesti gat or/i nstit uti o n 
s h o ul d pr o vi de t he I R B wit h a s u m mar y of t he st u d y’s o utc o me, a n d t he S p o ns or a n d re g ulat or y 
a ut h orit y(ies) wit h a n y re p orts re q uire d. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 5 9 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
1 3  C LI NI C A L S T U D Y R E P O R T A N D D A T A DI S C L O S U R E 
A C S R will be pr o d uce d u p o n c o m pleti o n of t he st u d y.  A c o or di nati n g I n vesti gat or will be 
desi g nate d t o re vie w a n d si g n t he c o m plete d C S R. 
I nf or mati o n a b o ut t his st u d y will be p oste d o n t he htt p://cli nicaltrials. g o v a n d 
htt ps:// w w w.cli nicaltrialsre gister.e u we bsites (if a p plica ble) a n d, w here a p plica ble, o n ot her 
we bsites re q uire d b y t he l ocal re g ulat or y a ut h orities of partici pati n g c o u ntries. 
It is i nte n de d t hat t he res ults fr o m t his researc h will be s u b mitte d t o a peer-re vie we d me dical 
p u blicati o n, o nce t he st u d y is c o m plete d. 
1 3. 1  Fi n al Re p ort 
W het her t he st u d y is c o m plete d or pre mat urel y ter mi nate d, t he S p o ns or will e ns ure t hat a C S R is 
pre pare d a n d pr o vi de d t o t he re g ulat or y a ge nc y(ies) as re q uire d b y t he a p plica ble re g ulat or y 
re q uire me nt(s).  T he S p o ns or will als o e ns ure t hat C S Rs i n mar keti n g a p plicati o ns meet t he 
sta n dar ds of t he I C H har m o nise d tri partite g ui deli ne E 3:  Str uct ure a n d c o nte nt of C S Rs. 
W here re q uire d b y a p plica ble re g ulat or y re q uire me nts, a n I n vesti gat or si g nat or y will be 
i de ntifie d f or t he a p pr o val of t he C S R.  T he I n vesti gat or will be pr o vi de d reas o na ble access t o 
statistical ta bles, fi g ures, a n d rele va nt re p orts, a n d ha ve t he o p p ort u nit y t o re vie w c o m plete st u d y 
res ults. 
A C S R will c o ntai n all data c ollecte d t hr o u g h t o t he E O S. 
U p o n c o m pleti o n of t he C S R(s), t he S p o ns or will pr o vi de t he I n vesti gat or(s) wit h t he fi nal 
a p pr o ve d C S R(s). 

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5 Ma y 2 0 2 1 
Pa ge 6 0 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
1 4  R E F E R E N C E S 
Alta y L, Sit nils ka 1 V, Sc hic k T, et al.  Earl y l ocal acti vati o n of c o m ple me nt i n a q ue o us h u m o ur 
of patie nts wit h a ge-relate d mac ular de ge nerati o n.  E ye ( L o n d).  2 0 1 9; 3 3( 1 2): 1 8 5 9- 1 8 6 4. 
A ver y R L, Ba kri SJ, Bl u me n kra nz M S, et al. I ntra vitreal i njecti o n tec h ni q ue a n d m o nit ori n g: 
u p date d g ui deli nes of a n e x pert pa nel.  Reti na.  2 0 1 4; 3 4 S u p ple me nt 1 2: S 1- S 1 8. 
Ba kri SJ, T h or ne J E, H o A C, et al.  Safet y a n d Efficac y of A nti- Vasc ular E n d ot helial Gr o wt h 
Fact or T hera pies f or Ne o vasc ular A ge- Relate d Mac ular De ge nerati o n: A Re p ort b y t he 
A merica n Aca de m y of O p ht hal m ol o g y.  O p ht hal m ol o g y.  2 0 1 9; 1 2 6( 1): 5 5- 6 3. 
Ba u mal C R, S pai de R F, Vajz o vic L, et al.  Reti nal Vasc ulitis a n d I ntra oc ular I nfla m mati o n after 
I ntra vitreal I njecti o n of Br ol uciz u ma b.  2 0 2 0; 1 2 7( 1 0): 1 3 4 5- 1 3 5 9. 
B L A 1 2 5 1 5 6 A vaila ble fr o m: 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/ n da/ 2 0 0 6/ 1 2 5 1 5 6s 0 0 0 0 _ L uce ntis _ P har m R. p df.  
Accesse d Oct o ber 2 0 1 9. 
B L A 1 2 5 3 8 7 A vaila ble fr o m: 
htt ps:// w w w.access data.f da. g o v/ dr u gsatf da _ d ocs/ n da/ 2 0 1 1/ 1 2 5 3 8 7 Ori g 1s 0 0 0 P har m R. p df.  
Accesse d Oct o ber 2 0 1 9. 
B orras C, Dela u na y K, Sla o ui Y, et al.  Mec ha nis ms of F H Pr otecti o n A gai nst Ne o vasc ular 
A M D.  Fr o ntiers i n I m m u n ol o g y.  2 0 2 0; 1 1: 4 4 3 
Br o dsz ki N, Frazer- A bel A, Gr u mac h A S, et al .  E ur o pea n S ociet y f or I m m u n o deficie ncies 
( E SI D) a n d E ur o pea n Refere nce Net w or k o n Rare Pri mar y I m m u n o deficie nc y, 
A ut oi nfla m mat or y a n d A ut oi m m u ne Diseases ( E R N RI T A) c o m ple me nt g ui deli ne: deficie ncies, 
dia g n osis, a n d ma na ge me nt.  J Cli n I m m u n ol.  2 0 2 0; 4 0( 4): 5 7 6- 5 9 1. 
Cali p pe B, A u g usti n S, Be g uier F, et al.  C o m ple me nt Fact or H I n hi bits C D 4 7- Me diate d 
Res ol uti o n of I nfla m mati o n.  I m m u nit y.  2 0 1 7; 4 6( 2): 2 6 1- 2 7 2. 
C ha vali V R, Di niz B, H ua n g J, Yi n g G S, Sa d da S R, Sta m b olia n D.  Ass ociati o n of O C T deri ve d 
dr use n meas ure me nts wit h A M D ass ociate d- ge n ot y pic S N Ps i n A mis h p o p ulati o n.  J Cli n Me d.  
 
C he n H, Y u K D, X u G Z.  Ass ociati o n bet wee n Varia nt Y 4 0 2 H i n A ge- Relate d Mac ular 
De ge nerati o n ( A M D) S usce pti bilit y Ge ne C F H a n d Treat me nt Res p o nse of A M D: A Meta-
A nal ysis.  Pl o S O N E 2 0 1 2; 7( 8): e 4 2 4 6 4.  d oi: 1 0. 1 3 7 1/j o ur nal. p o ne. 0 0 4 2 4 6 4 
Di n g J D, Kell y U, La n d o ws ki M, et al.  E x pressi o n of h u ma n c o m ple me nt fact or H pre ve nts a ge-
relate d mac ular de ge nerati o n-li ke reti na da ma ge a n d ki d ne y a b n or malities i n a ge d Cf h k n oc k o ut 
mice.  A m J Pat h ol.  2 0 1 5; 1 8 5( 1): 2 9- 4 2. 
E ur o pea n U ni o n ( E U) Directi ves 2 0 0 1/ 2 0/ E C. 
E ur o pea n U ni o n ( E U) Directi ves 2 0 0 5/ 2 8/ E C. 
Ga u drea ult J, Fei D, R usit J, S u b oc P, S hi u V. Precli nical p har mac o ki netics of Ra ni biz u ma b 
(r h u Fa b V 2) after a si n gle i ntra vitreal a d mi nistrati o n.  I n vest O p ht hal m ol Vis Sci.  
2 0 0 5 ; 4 6( 2) : 7 2 6 3 3. 
Geerli n gs MJ, de J o n g E K, de n H olla n der AI.  T he c o m ple me nt s yste m i n a ge-relate d mac ular 
de ge nerati o n : A re vie w of rare ge netic varia nts a n d i m plicati o ns f or pers o nalize d treat me nt.  
M olec I m m u n ol.  2 0 1 7 ; 8 4 : 6 5- 7 6. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 6 1 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
Gillies M, H u n y or A, Ar n ol d J, et al.  Mac ular Atr o p h y i n Ne o vasc ular A ge- Relate d Mac ular 
De ge nerati o n : A Ra n d o mize d Cli nical Trial C o m pari n g Ra ni biz u ma b a n d Afli berce pt ( RI V A L 
St u d y).  O p ht hal m ol o g y 2 0 2 0; 1 2 7( 2): 1 9 8- 2 1 0. 
H ole ka m p N. Re vie w of Ne o vasc ular A ge- Relate d Mac ular De ge nerati o n Treat me nt O pti o ns.  
A m J Ma na g Care.  2 0 1 9 ; 2 5( 1 0 S u p pl) : S 1 7 2- S 1 8 1. 
I V E RI C bi o’s Zi m ura ®, a N o vel C o m ple me nt C 5 I n hi bit or, Met its Pri mar y E n d p oi nt a n d 
Reac he d Statistical Si g nifica nce i n a P hase 2 b Ra n d o mize d, C o ntr olle d Cli nical Trial i n 
Ge o gra p hic Atr o p h y Sec o n dar y t o Dr y A ge- Relate d Mac ular De ge nerati o n [ Press release].  Ne w 
Y or k, N Y: I V E RI C bi o; Oct o ber 2 8, 2 0 1 9.  htt ps://i n vest ors.i veric bi o.c o m/ ne ws-releases/ ne ws-
release- details/i veric- bi os-zi m urar- n o vel-c o m ple me nt-c 5-i n hi bit or- met-its.  Accesse d Ma y 1 3, 
2 0 2 0. 
Jaffe GJ, Eli ott D, Wells J A, Pre n ner J L, Pa p p A, Patel S.  A P hase 1 St u d y of I ntra vitre o us 
E 1 0 0 3 0 i n C o m bi nati o n wit h Ra ni biz u ma b i n Ne o vasc ular A ge- Relate d Mac ular De ge nerati o n. 
O p ht hal m ol o g y.  2 0 1 6; 1 2 3( 1): 7 8- 8 5. 
Jaffe GJ, West b y K, Csa k y K G, et al.  C 5 I n hi bit or a vaci nca pta d pe g ol f or ge o gra p hic atr o p h y 
d ue t o a ge-relate d mac ular de ge nerati o n: A ra n d o mize d pi v otal P hase 2/ 3 Trial.  O p ht hal m ol o g y.  
Pre pri nt 2 0 2 0.  d oi: htt ps:// d oi. or g/ 1 0. 1 0 1 6/j. o p ht ha. 2 0 2 0. 0 8. 0 2 7 
Keir L S, Firt h R, A p o ni k L, et al.  V E G F re g ulates l ocal i n hi bit or y c o m ple me nt pr otei ns i n t he 
e ye a n d ki d ne y.  J Cli n I n vest.  2 0 1 7; 1 2 7( 1): 1 9 9- 2 1 4. 
K ha na ni A M, S kell y A, Bezl ya k V, Gri ner R, T orres L R, Sa g kri otis A.  SI E R R A- A M D: A 
Retr os pecti ve, Real- W orl d E vi de nce St u d y of Patie nts wit h Ne o vasc ular A ge- Relate d Mac ular 
De ge nerati o n i n t he U nite d States.  O p ht hal m ol Reti na.  2 0 2 0; 4( 2): 1 2 2- 1 3 3. 
Kr o h ne T U, Li u Z, H olz F G, Me yer C H.  I ntra oc ular p har mac o ki netics of ra ni biz u ma b f oll o wi n g 
a si n gle i ntra vitreal i njecti o n i n h u ma ns.  A m J O p ht hal m ol.  2 0 1 2; 1 5 4: 6 8 2- 6 8 6. 
La n d o ws ki M, Kell y U, Ki n ge b or n M, et al.  H u ma n c o m ple me nt fact or H 4 0 2 H p ol y m or p his m 
ca uses a n a ge-relate d mac ular de ge nerati o n p he n ot y pe a n d li p o pr otei n d ysre g ulati o n i n mice. 
P N A S.  2 0 1 9; 1 1 6( 9): 3 7 0 3- 3 7 1 1. 
Lia o D S, Gr ossi F V, El Me h di D, et al.  C o m ple me nt C 3 I n hi bit or Pe gcetac o pla n f or Ge o gra p hic 
Atr o p h y Sec o n dar y t o A ge- Relate d Mac ular De ge nerati o n: A Ra n d o mize d P hase 2 Trial.  
O p ht hal m ol.  2 0 2 0; 1 2 7( 2): 1 8 6- 1 9 5. 
Matta pallil MJ a n d Cas pi R R.  C o m pli me nts of Fact or H: W hat’s i n it f or A M D? I m m u nit y. 
2 0 1 7: 4 6( 2): 1 6 7- 1 6 9. 
Merle M B, R os ner B, Se d d o n J M.  Ge netic s usce pti bilit y, diet q ualit y, a n d t w o-ste p pr o gressi o n 
i n dr use n size.  I n vesti gati ve O p ht hal m ol o g y & Vis ual Scie nce.  2 0 2 0; 6 1( 5), Article 1 7: 1- 1 2. 
Sa d da S R, T u o mi L L, Di n g B, F u n g A E, H o p ki ns JJ.  Mac ular Atr o p h y i n t he H A R B O R St u d y 
f or Ne o vasc ular A ge- Relate d Mac ular De ge nerati o n.  O p ht hal m ol o g y.  2 0 1 8; 1 2 5( 6): 8 7 8- 8 8 6. 
Sa h ni J, D u gel P U, Patel S S, et al.  Safet y a n d Efficac y of Differe nt D oses a n d Re gi me ns of 
Farici ma b vs Ra ni biz u ma b i n Ne o vasc ular A ge- Relate d Mac ular De ge nerati o n: T he A V E N U E 
P hase 2 Ra n d o mize d Cli nical Trial.  J A M A O p ht hal m ol.  2 0 2 0; 1 3 8( 9): 1- 1 0. 
Sc hic k T, Stei n ha uer M, Asla ni dis A et al.  L ocal c o m ple me nt acti vati o n i n a q ue o us h u m or i n 
patie nts wit h a ge-relate d mac ular de ge nerati o n.  E ye ( L o n d).  2 0 1 7; 3 1( 5): 8 1 0- 8 1 3. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 6 2 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
S h ort B G.  Safet y E val uati o n of Oc ular Dr u g Deli ver y F or m ulati o ns: Tec h ni q ues a n d Practical 
C o nsi derati o ns.  T o xic ol Pat h ol.  2 0 0 8; 3 6: 4 9- 6 2. 
Ste ve ns S, Gil bert C, Ast b ur y N.  H o w t o meas ure i ntra oc ular press ure: a p pla nati o n t o n o metr y.  
C o m m u nit y E ye Healt h.  2 0 0 8; 2 0( 6 4): 7 4 – 7 5.  C orrecti o n i n: C o m m u nit y E ye Healt h.  2 1( 6 6): 3 4. 
T he U nite d States ( U S) C o de of Fe deral Re g ulati o ns ( C F R), Title 2 1, Parts 5 0 a n d 3 1 2 ( 2 1 C F R 
5 0, 2 1 C F R 3 1 2). 
Trie b wasser M P, R o bers o n E D, Y u Y, et al.  Rare Varia nts i n t he F u ncti o nal D o mai ns of 
C o m ple me nt Fact or H Are Ass ociate d wit h A ge- Relate d Mac ular De ge nerati o n.  I n vest 
O p ht hal m ol Vis Sci.  2 0 1 5; 5 6( 1 1): 6 8 7 3- 7 8. 
W orl d Healt h Or ga nizati o n.  Pri orit y e ye diseases.  Accesse d 0 3 Oct o ber 2 0 1 9.  
htt ps:// w w w. w h o.i nt/ bli n d ness/ca uses/ pri orit y/e n/i n de x 7. ht ml 
X u W W, H ua n g Y F, Wa n g L Q, Z ha n g M N.  C ycl o pe x y vers us vitrect o m y c o m bi ne d wit h 
i ntra oc ular ta m p o na de f or treat me nt of c ycl o dial ysis. I nt J O p ht hal m ol.  2 0 1 3; 6( 2): 1 8 7- 9 2. 
Y u C, R o u bei x C, Se n nla u b F, Sa ba n D R. Micr o glia vers us M o n oc ytes: Disti nct R oles i n 
De ge nerati ve Diseases of t he Reti na.  Tre n ds i n Ne ur oscie nces.  2 0 2 0; 4 3( 6): 4 3 3- 4 4 9. 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 6 3 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
1 5  A P P E N DI C E S 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 6 5 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A b br e viati o ns:  A D A =a nti dr u g a nti b o dies; A E =a d verse e ve nt; B C V A = best c orr ecte d vis ual ac u it y; C F H =c o m ple me nt f act or H; E C =e xcl usi o n criteria; 
E C G =electr ocar di o gr a m; E O S = E n d of St u d y; E T D R S = E arl y Tr eat me nt Dia betic Reti n o pat h y St u d y; hr = h o ur; I C =i ncl usi o n criteria; I O P = i ntr a oc ular pr ess ure; 
L L V A =l o w l u mi na nce vis ual ac uit y; M N Re a d = Mi n nes ota L o w- visi o n Rea di n g T est; N EI V F Q- 2 5 = Nati o nal E ye I nstit ute Vis ual F u ncti o ni n g Q uesti o n nair e- 2 5; 
O C T = o ptical c o her e nce t o m o gr a p h y; O C T- A = O C T a n gi o gr a p h y; O U = oc ul us uter q ue ( b ot h e yes; e y es will be teste d se par atel y); S A E =ser i o us a d verse e ve nt; 
S D- O C T =s pe ctr al d o mai n O C T; S E =st u d y e ye; S o C =sta n dar d of car e ( 2 m g afli ber ce pt e ver y ot her m o nt h); V A = vis ual ac uit y  
* Assess me nt o btai ne d pri or t o d osi n g, as a p plica ble.  
* * I ma gi n g ( c ol or f u n d us p h ot o gr a p h y, f u n d us a ut ofl u or esce nce, fl u or escei n a n gi o gr a p h y, near i nfr are d r eflecta nce i ma gi n g, S D- O C T) s h o ul d be r e peate d at 
baseli ne if > 2 8 da ys after scr ee ni n g asse ss me nt, or desir e d b y t he I n vesti gat or. 
† Ra n d o mizati o n ma y occ ur u p t o 2 da ys pri or t o t he baseli ne visit. 
a  
Bl o o d sa m pli n g f or e x pl or at or y ge netics will occ ur pri or t o first d osi n g. 
b  
I nf or me d c o nse nt m ust be o btai ne d bef or e a n y st u d y assess me nt is perf or me d. 
c  
Me dical a n d oc ular hist or y als o i ncl u des s ocial hist or y a n d f a mil y o p ht hal mic hist or y ( Secti o n 5. 1. 3 ). 
d  
S o me e ntr y criteria a p pl y o nl y t o t he S E.  T her ef ore, t he S E m ust be i de ntifie d d uri n g t he scree ni n g pr ocess i n or der t o assess e ntr y criteria (Secti o n 5. 4 ). 
e  
Vital si g n meas ur e me nts i ncl u de s yst olic a n d diast olic bl o o d press ur es, heart r ate, r es pir at or y r ate, a n d b o d y te m per at ur e.  T he s u bject will be seate d f or at 
least 5 mi n utes bef or e all meas ur e me nts ar e ta ke n.  W he n pr oce d ur es o verla p a n d ar e sc he d ule d t o occ ur at t he sa me ti me p oi nt, vital si g n meas ure me nts 
s h o ul d pr ece de a n y bl o o d c ollecti o n (Secti o n 5. 1. 7 ). 
f  
N o I P/ S ha m tr eat me nt will be gi ve n at t he 4 8- wee k E O S visit; h o we ver, afli ber ce pt S o C s h o ul d be a d mi nister e d as cli nicall y i n d icate d.  It is acce pta ble f or a 
diff er e nt a nti- V E G F t her a p y t o be a d mi nister e d at t h is visit per t he i n vesti gator’s cli nical j u d ge me nt.    
g  
A Es will be r e p orte d f or a mi ni m u m of 3 0 da ys after t he last a dmi nistr ati o n of st u d y tr eat me nt.  If a s u bject e x perie nces a n S A E t hat is c o nsi der e d t o be 
r elate d t o st u d y tr eat me nt at a n y ti me after t he stu d y, it m ust be r e p orte d t o t he S p o ns or.  See Secti o n 7. 3  f or f ull A E re p orti n g pr oce d ur es. 
h  
C o m plete o p ht hal mic e xa mi nati o ns of b ot h t he st u d y a n d f ell o w e ye will i ncl u de  a n assess me nt of t he V A a n d vis ual f u ncti o n usin g vali date d assess me nt 
t o ols, a c o m plete o p ht hal mic bi o micr osc o p y e xa mi nati o n i ncl u di n g f u n d us e xa mi nati o n, I OP, a n d oc ular i ma gi n g tests t o vis ualize  t he a p pear a nce a n d 
pat h ol o g y of t he r eti na a n d ass ociate d oc ular tiss ues ( Secti o n 5. 1. 6 ). 
i 
O n d osi n g da ys, I O P assess me nts ar e o btai ne d pri or t o t he d ose O U, a n d 3 0 ± 1 5 mi n utes after t he d ose o nl y i n t he S E ( O U o pti o nal ).  A n a d diti o nal 
assess me nt fr o m t he S E s h o ul d be ta ke n at 6 0 ±
 m m H g at t he 3 0- mi n ute assess me nt.  If t he I O P c o nti n ues t o 
e xcee d 3 0 m m H g, t he n sta n dar d I O P-
 
tr eate d per i nstit uti o nal g ui deli nes.  Re gar dless of w het her a p pla nati o n t o n o metr y or a T o n o- Pe n®  is use d t o meas ur e I O P, t he sa me met h o d s h o ul d be use d 
f or t he s u bject f or t he e ntiret y of t heir partici pati o n i n t his st u d y. 
j  
E T D R S B C V A a n d B C V A L L V A will be perf or me d b y mas ke d assess ors.  
k  
T hese baseli ne i ma gi n g assess me nts ar e o nl y r e q uir e d if t he scr ee nin g i ma ges wer e o btai ne d > 2 8 da ys pri or t o baseli ne.  T he y m a y be r e d o ne at baseli ne if 
t he I n vesti gat or dee ms it cli nicall y rele va nt, or if t her e were q ualit y iss ues wit h t he scree ni n g i ma ges. 
l  
Baseli ne assess me nt of fl u or escei n a n gi o gr a p h y is n ot r e q uir e d, b ut ma y be assesse d if t he I n vesti gat or dee ms it cli nicall y r ele va nt, or if t her e were q ualit y 
iss ues wit h t he scree ni n g i ma ges. 
m 
Assess me nt is o pti o nal a n d w ill o nl y be c o n d ucte d if t he site has a p pr o val fr o m t he S p o ns or. 
n 
Assess me nt will be perf or me d as descri be d i n A p pe n di x I . 
o  
Assess me nt will be perf or me d as descri be d i n A p pe n di x J . 
p 
Hi g hl y se nsiti ve (ser u m or uri ne) h u ma n c h ori o nic g o na d otr o pi n pr e g na nc y test as nee de d f or w o me n of c hil d beari n g p ote ntial. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 6 6 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
q  
Cli nical saf et y la b or at or y assess me nts i ncl u de t he f oll o wi n g: he mat ol o g y ( platelet c o u nt, r e d bl o o d cell c o u nt, he m o gl o bi n c o u nt, he mat ocrit, mea n 
c or p usc ular v ol u me, mea n c or p usc ular he m o gl o bi n, per ce nt r etic ul oc ytes, a n d w hite bl o o d cell c o u nt  wit h diff er e ntial) a n d cli nical c he mistr y ( bl o o d urea 
nitr o ge n, cr eati ni ne, gl uc ose, p otassi u m, s o di u m, t otal calci u m, as partate a mi n otr a nsf er ase, ala ni ne a mi n otr a nsf er ase, al kali ne p h os p hatase, t otal a n d dir ect 
bilir u bi n, t otal pr otei n, sta n dar d electr o l ytes – ma g nesi u m, p h os p hate, a n d c hl ori de). 
r  
R o uti ne uri nal ysis i ncl u des macr osc o pic a n d micr osc o pic e xa mi nati o n. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 6 7 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x B:  Bi ol o gic al S a m ple C ollecti o n a n d S hi p pi n g I nstr ucti o ns 
Bi ol o gic al S a m ples 
W h ole bl o o d a n d a q ue o us h u m or sa m ples f or t he assess me nt of c o m ple me nt pr otei n 
c o nce ntrati o ns (s uc h as, b ut n ot li mite d t o, c o m ple me nt fact or H, c o m ple me nt fact or I, 
c o m ple me nt fact or B, c o m ple me nt c o m p o ne nt 3); D N A a n d cells; a n d sa m ples f or ser u m 
c he mistr y will be c ollecte d at t he ti me p oi nts s pecifie d i n t he S O A i n A p pe n di x A . 
Refer t o t he la b orat or y ma n ual f or detaile d sa m ple c ollecti o n, st ora ge, a n d s hi p pi n g i nstr ucti o ns.  
All necessar y tra nsfer t u bes, Vac utai ner ® t u bes, la bels, s hi p pi n g b o xes, a n d f or ms, will be 
pr o vi de d b y t he ce ntral la b orat or y. 
A nteri or C h a m ber ( A q ue o us H u m or) S a m ple C ollecti o n 
T he f oll o wi n g pr oce d ures will be f oll o we d: 
 T he a q ue o us h u m or parace ntesis sa m ples will be c ollecte d usi n g ase ptic tec h ni q ue b y a 
q ualifie d p h ysicia n f oll o wi n g t he i nstr ucti o ns o utli ne d i n t he p har mac y ma n ual. 
 T he a q ue o us h u m or sa m ple c ollecti o n c o nsists of a n a nteri or c ha m ber parace ntesis ( A C P) 
(re m o vi n g a p pr o xi matel y 0. 1 m L of a q ue o us fl ui d fr o m t he a nteri or c ha m ber of t he e ye).  
T he pr oce d ure will be perf or me d b y passi n g a nee dle t hr o u g h t he li m b us usi n g t he 
p h ysicia n’s a nest hesia of c h oice f oll o wi n g a p plicati o n of t o pical a nti- bacterial s ol uti o n 
i nstr ucti o ns).   
Please refer t o la b orat or y ma n ual f or a d diti o nal details o n ha n dli n g of c ollecte d sa m ples. 
Sa m ples will be c ollecte d wit h t he kit pr o vi de d b y t he ce ntral la b orat or y a n d s hi p pe d o n dr y ice 
t o t he ce ntral la b orat or y as s o o n as p ossi ble after t he dra w. 
T he sa m ples will be a p pr o xi matel y 1 0 0 μ L, w hic h is e x pecte d t o be well-t olerate d wit h o ut pai n 
or ot her si de effects. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 6 8 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x C:  C ol or F u n d us P h ot o gr a p h y ( C F P) 
Sc o pe: 
C ol or f u n d us p h ot o gra p hs will be ta ke n b y trai ne d pers o n nel at t he st u d y sites.  F u n d us 
p h ot o gra p h y will be perf or me d at t he i nter vals s pecifie d i n t he S O A i n A p pe n di x A .  A nal ysis of 
f u n d us p h ot o gra p hs will be perf or me d b y t he I ma ge Rea di n g Ce nter. 
E q ui p me nt: 
See t he I ma ge Rea di n g Ce nter ma n ual. 
Pr oce d ure: 
T he I ma ge Rea di n g Ce nter will pr o vi de a ma n ual a n d trai ni n g materials.  T he f u n d us 
p h ot o gra p her a n d p h ot o gra p h y e q ui p me nt will be certifie d b y t he rea di n g ce nter bef ore a n y st u d y 
i ma ges are ta ke n.  See t he I ma ge Rea di n g Ce nter ma n ual f or f urt her details. 
St u d y site m ust ma ke best eff ort t o use t he sa me assess or t hr o u g h o ut t he st u d y f or eac h s u bject.  
If a differe nt assess or is use d f or t he sa me s u bject, t he rati o nale m ust be clearl y mar ke d i n t he 
s u bject’s st u d y bi n der a n d ma de a vaila ble if re q ueste d. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 6 9 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x D:  F u n d us A ut ofl u oresce nce ( F A F) 
Sc o pe: 
F A F will be perf or me d b y trai ne d pers o n nel at t he st u d y site w h o are certifie d b y t he 
I ma ge Rea di n g Ce nter.  F A F i ma gi n g will be o btai ne d at t he i nter vals s pecifie d i n t he S O A 
(A p pe n di x A ).  A nal ysis of F A F i ma ges will be perf or me d b y t he I ma ge Rea di n g Ce nter. 
E q ui p me nt: 
Di gital i ma gi n g s yste ms are re q uire d as descri be d i n t he I ma ge Rea di n g Ce nter ma n ual.  T he 
s yste m a n d s oft ware at t he site will be certifie d b y t he I ma ge Rea di n g Ce nter pri or t o o btai ni n g 
a n y st u d y i ma ges.  T his certificati o n a n d vali dati o n pr ocess will e ns ure t hat t he I ma ge Rea di n g 
Ce nter will be a ble t o c orrectl y calc ulate t he re q uire d meas ure me nts. 
N o pri nte d F A F i ma ges will be se nt t o t he I ma ge Rea di n g Ce nter. 
Pr oce d ures a n d Certificati o n: 
T he I ma ge Rea di n g Ce nter will pr o vi de a ma n ual.  T he F A F p h ot o gra p her a n d e q ui p me nt, 
s yste ms, a n d s oft ware will be certifie d b y t he rea di n g ce nter bef ore a n y st u d y i ma ges are ta ke n.  
See t he I ma ge Rea di n g Ce nter ma n ual f or f urt her details. 
St u d y site m ust ma ke best eff ort t o use t he sa me assess or t hr o u g h o ut t he st u d y f or eac h s u bject.  
If a differe nt assess or is use d f or t he sa me s u bject, t he rati o nale m ust be clearl y mar ke d i n t he 
s u bject’s st u d y bi n der a n d ma de a vaila ble if re q ueste d. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 0 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x E:  Fl u orescei n A n gi o gr a p h y ( F A) 
Sc o pe: 
F A will be perf or me d b y trai ne d pers o n nel at t he st u d y site w h o are certifie d b y t he I ma ge 
Rea di n g Ce nter.  T he fl u orescei n a n gi o gra ms will be o btai ne d at t he i nter vals s pecifie d i n t he 
S O A ( A p pe n di x A ).  A nal ysis of F As will be perf or me d b y t he I ma ge Rea di n g Ce nter. 
E q ui p me nt: 
Di gital a n gi o gra ms m ust be use d w hile c o n d ucti n g a n a n gi o gra p hic e val uati o n f or t he st u d y.  
Fil m- base d a n gi o gra p h y is n ot acce pta ble. 
Di gital i ma gi n g s yste ms are re q uire d.  T he s yste m a n d s oft ware at t he site will be certifie d b y t he 
I ma ge Rea di n g Ce nter pri or t o o btai ni n g a n y st u d y a n gi o gra ms.  T his certificati o n a n d vali dati o n 
pr ocess will e ns ure t hat t he I ma ge Rea di n g Ce nter will be a ble t o c orrectl y calc ulate t he re q uire d 
meas ure me nts. 
Pr oce d ures: 
T he I ma ge Rea di n g Ce nter will pr o vi de a ma n ual a n d trai ni n g materials.  T he p h ot o gra p her a n d 
p h ot o gra p h y e q ui p me nt, s yste ms a n d s oft ware will be certifie d b y t he I ma ge Rea di n g Ce nter 
bef ore a n y st u d y i ma ges are ta ke n.  See t he I ma ge Rea di n g Ce nter ma n ual f or f urt her details. 
St u d y site m ust ma ke best eff ort t o use t he sa me assess or t hr o u g h o ut t he st u d y f or eac h s u bject.  
If a differe nt assess or is use d f or t he sa me s u bject, t he rati o nale m ust be clearl y mar ke d i n t he 
s u bject’s st u d y bi n der a n d ma de a vaila ble if re q ueste d. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 1 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x F:  S pectr al D o m ai n O ptic al C o here nce T o m o gr a p h y ( S D- O C T) 
Sc o pe: 
S D- O C T will be perf or me d b y trai ne d pers o n nel at t he st u d y site w h o are certifie d b y t he I ma ge 
Rea di n g Ce nter.  S D- O C T i ma gi n g will be o btai ne d at t he i nter vals s pecifie d i n t he S O A 
(A p pe n di x A ) a n d f or war de d t o t he I ma ge Rea di n g Ce nter. 
E q ui p me nt: 
Di gital i ma gi n g s yste ms are re q uire d as descri be d i n t he I ma ge Rea di n g Ce nter ma n ual.  T he 
s yste m a n d s oft ware at t he site will be certifie d b y t he I ma ge Rea di n g Ce nter pri or t o o btai ni n g 
a n y st u d y i ma ges.  T his certificati o n a n d vali dati o n pr ocess will e ns ure t hat t he I ma ge Rea di n g 
Ce nter will be a ble t o c orrectl y calc ulate t he re q uire d meas ure me nts.   
N o pri nte d S D- O C T i ma ges will be se nt t o t he I ma ge Rea di n g Ce nter. 
Pr oce d ures a n d Certificati o n: 
T he I ma ge Rea di n g Ce nter will pr o vi de a ma n ual a n d trai ni n g materials.  T he S D- O C T 
tec h nicia n a n d e q ui p me nt, s yste ms, a n d s oft ware will be certifie d b y t he I ma ge Rea di n g Ce nter 
bef ore a n y st u d y i ma ges are ta ke n.  See t he I ma ge Rea di n g Ce nter ma n ual f or f urt her details. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 2 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x G:  O ptic al C o here nce T o m o gr a p h y – A n gi o gr a m ( O C T- A) 
Sc o pe: 
O C T- A will be perf or me d b y trai ne d pers o n nel at t he st u d y site w h o are certifie d b y t he I ma ge 
Rea di n g Ce nter.  O C T- A i ma gi n g will be o btai ne d at t he i nter vals s pecifie d i n t he S O A 
(A p pe n di x A ) a n d f or war de d t o t he I ma ge Rea di n g Ce nter. 
E q ui p me nt: 
Di gital i ma gi n g s yste ms are re q uire d as descri be d i n t he I ma ge Rea di n g Ce nter ma n ual.  T he 
s yste m a n d s oft ware at t he site will be certifie d b y t he I ma ge Rea di n g Ce nter pri or t o o btai ni n g 
a n y st u d y i ma ges.  T his certificati o n a n d vali dati o n pr ocess will e ns ure t hat t he I ma ge Rea di n g 
Ce nter will be a ble t o c orrectl y calc ulate t he re q uire d meas ure me nts. 
N o pri nte d O C T- A i ma ges will be se nt t o t he I ma ge Rea di n g Ce nter. 
Pr oce d ures a n d Certificati o n: 
T he I ma ge Rea di n g Ce nter will pr o vi de a ma n ual a n d trai ni n g materials.  T he O C T- A tec h nicia n 
a n d e q ui p me nt, s yste ms, a n d s oft ware will be certifie d b y t he I ma ge Rea di n g Ce nter bef ore a n y 
st u d y i ma ges are ta ke n.  See t he I ma ge Rea di n g Ce nter ma n ual f or f urt her details. 
St u d y site m ust ma ke best eff ort t o use t he sa me assess or t hr o u g h o ut t he st u d y f or eac h s u bject.  
If a differe nt assess or is use d f or t he sa me s u bject, t he rati o nale m ust be clearl y mar ke d i n t he 
s u bject’s st u d y bi n der a n d ma de a vaila ble if re q ueste d. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 3 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x H:  Ne ar I nfr are d Reflect a nce I m a gi n g ( NI R) 
Sc o pe: 
NI R i ma ges are ta ke n t o c o m ple me nt t he I ma ge Rea di n g Ce nter rea di n g ce nter e val uati o n of 
f u n d us a ut ofl u oresce nce i ma ges. 
NI R will be perf or me d b y trai ne d pers o n nel at t he st u d y site w h o are certifie d b y t he I ma ge 
Rea di n g Ce nter.  NI R will be o btai ne d at t he i nter vals s pecifie d i n t he S O A ( A p pe n di x A ) a n d 
f or war de d t o t he I ma ge Rea di n g Ce nter. 
E q ui p me nt: 
Di gital i ma gi n g s yste ms are re q uire d as descri be d i n t he I ma ge Rea di n g Ce nter ma n ual.  T he 
s yste m a n d s oft ware at t he site will be certifie d b y t he I ma ge Rea di n g Ce nter pri or t o o btai ni n g 
a n y st u d y i ma ges.  T his certificati o n a n d vali dati o n pr ocess will e ns ure t hat t he I ma ge Rea di n g 
Ce nter will be a ble t o c orrectl y calc ulate t he re q uire d meas ure me nts. 
N o pri nte d NI R i ma ges will be se nt t o t he I ma ge Rea di n g Ce nter. 
Pr oce d ures a n d Certificati o n: 
T he I ma ge Rea di n g Ce nter will pr o vi de a ma n ual a n d trai ni n g materials.  T he NI R tec h nicia n 
a n d e q ui p me nt, s yste ms, a n d s oft ware will be certifie d b y t he I ma ge Rea di n g Ce nter bef ore a n y 
st u d y i ma ges are ta ke n.  See t he I ma ge Rea di n g Ce nter ma n ual f or f urt her details. 
St u d y site m ust ma ke best eff ort t o use t he sa me assess or t hr o u g h o ut t he st u d y f or eac h s u bject.  
If a differe nt assess or is use d f or t he sa me s u bject, t he rati o nale m ust be clearl y mar ke d i n t he 
s u bjects’ st u d y bi n der a n d ma de a vaila ble if re q ueste d. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 4 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x I:  Mi n nes ot a L o w- visi o n Re a di n g Test ( M N Re a d) C h arts 
M N Re a d Re a di n g S pee d Assess me nt 
T he M N Rea d ac uit y car ds are c o nti n u o us-te xt rea di n g ac uit y car ds s uita ble f or meas uri n g t he 
rea di n g ac uit y a n d rea di n g s pee d of n or mal a n d l o w- visi o n s u bjects.  T hese car ds were 
de vel o pe d at t he Mi n nes ota La b orat or y f or L o w- Visi o n Researc h, U ni versit y of Mi n nes ota, 
Mi n nea p olis, Mi n nes ota, i n researc h f u n de d b y t he Nati o nal I nstit utes of Healt h. 
Meas uri n g Rea di n g S pee d: 
T he M N Rea d ac uit y car ds c o nsist of si n gle, si m ple se nte nces wit h e q ual n u m bers of c haracters.  
T he pri nt is a pr o p orti o nall y s pace d f o nt, si milar t o t hat f o u n d i n ma n y ne ws pa pers a n d b o o ks.  
T he car ds c o ntai n se nte nces wit h 1 9 differe nt pri nt sizes.  T he te xt is pri nte d wit h hi g h c o ntrast 
 c haracters (i ncl u di n g s pace bet wee n eac h w or d 
a n d t he e n d of eac h li ne) pri nte d as 3 li nes wit h e ve n left a n d ri g ht mar gi ns.  T he v oca b ul ar y 
use d i n t he se nte nces are selecte d fr o m w or ds a p peari n g wit h hi g h fre q ue nc y i n sec o n d- t o 
t hir d- gra de rea di n g materials. 
E q ui p me nt: 
M N Rea d ac uit y car ds are use d t o meas ure rea di n g s pee d at differe nt pri nt sizes t o deter mi ne t he 
pri nt t hat s u p p orts t he s u bject’s ma xi m u m rea di n g s pee d.  A st o p watc h is re q uire d t o rec or d ti me 
t o a te nt h of a sec o n d.  A n easel or a dj usta ble sta n d ma y be nee de d f or s o me s u bjects.   
Testi n g: 
Car d Ill u mi nati o n: 
T he car ds s h o ul d be e ve nl y lit s o t hat n o s ha d o ws or glare will i nterfere wit h rea di n g.  T he 
l u mi na nce of t he w hite bac k gr o u n d o n t he car ds s h o ul d be bet wee n 8 0- 1 2 0 c d/ m2. 
Vie wi n g Dista nce: 
T he pri nt sizes a n d mar ki n gs o n t he car ds are desi g ne d f or a testi n g dista nce of 4 0 c m, b ut ma y 
be teste d at a dista nce of 3 2 c m.  We rec o m me n d usi n g a hea drest set t o t he a p pr o priate vie wi n g 
dista nce i n fr o nt of t he car ds, t o pre ve nt t he s u bject fr o m cree pi n g f or war d t hr o u g h o ut t he test.  
F or s u bjects wit h ce ntral fiel d l oss, we fi n d it easier t o all o w t he s u bject t o p ositi o n t he M N Rea d 
car d s o t hat t he se nte nce t o be rea d will fall i nt o t heir preferre d l ocati o n f or rea di n g. 
Testi n g Pr oce d ure: 
T he M N Rea d assess me nt will be c o n d ucte d first i n eac h e ye se paratel y a n d t he n wit h b ot h e yes 
o pe n.  A differe nt car d m ust be use d f or eac h test t o pre ve nt me m orizati o n of t he pri nte d 
material.  R otate car ds fr o m o ne e xa mi nati o n t o a n ot her t o var y t he te xt f or eac h e ye.  C o n d uct 
t he rea di n g tests i n t he f oll o wi n g or der.  Start b y testi n g t he ri g ht e ye wit h t he left e ye occl u de d.  
Ne xt, c o n d uct t he s pee d-rea di n g test i n t he left e ye wit h t he ri g ht e ye occl u de d, a n d lastl y wit h 
b ot h e yes o pe n. 
T he car d s h o ul d be rea d fr o m a dista nce of e xactl y 3 2 c m.  T o kee p t he testi n g dista nce c o nsta nt, 
use a piece of tra ns pare nt fis hi n g li ne, pre- meas ure d at 3 2 c m fr o m t he car d.  Meas ure t he 3 2 c m 
t o t he s u bject’s e ye b y h ol di n g t he fis hi n g li ne parallel t o t he fl o or.  A r uler or 3 2 c m meas uri n g 
de vice ma y als o be use d t o set a n d m o nit or t he dista nce.  I nstr uct t he s u bject t hat t he car d ma y be 
m o ve d u p a n d d o w n or si de t o si de, b ut n ot cl oser or fart her fr o m t he e yes.  T he car d m ust 
re mai n u pri g ht a n d m ust n ot tilt a wa y fr o m or t o war d t he s u bjects.  Eit her t he s u bject or t he 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 5 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
e xa mi ner ma y h ol d t he car d, de pe n di n g o n t he p h ysical a bilit y of t he s u bject.  Alter nati vel y, t he 
car d ma y be place d o n a n easel or a dj usta ble sta n d. 
C hec k t o e ns ure t hat t he rea di n g car d n u m ber o n t he sc ori n g s heet c orres p o n ds t o t he rea di n g 
car d n u m ber t hat y o u are usi n g.  T he M N Rea d sc ori n g s heet c o ntai ns t he test se nte nces 
c orres p o n di n g t o t he car d be gi n ni n g o n t he left- ha n d c ol u m n i n desce n di n g or der of ac uit y.  
I n dicate w hic h e ye is bei n g teste d.  Start wit h t he lar gest se nte nce a n d m o ve o nt o t he s u bse q ue nt 
se nte nces.  Kee p g oi n g u ntil t he s u bject ca n n ot rea d a n y w or ds i n a se nte nce.  Use a bla n k car d 
t o c o ver eac h se nte nce as y o u w or k y o ur wa y d o w n t he car d:  u nc o ver t he se nte nce t o be rea d 
w he n y o u sa y “start.”  Prese nt t he test se nte nce; si m ulta ne o usl y, tell t he s u bject t o start rea di n g 
a n d acti vate t he st o p watc h t o start t he ti mer.  As t he s u bject rea ds t he te xt, stri ke o ut w or ds n ot 
rea d, n ot atte m pte d, or rea d i nc orrectl y.  Use a st o p watc h t o rec or d t he ti me ta ke n t o rea d eac h 
se nte nce (t o t he nearest 0. 1 sec o n d). 
I nstr ucti o ns t o t he S u bject: 
“ W he n I sa y ‘start,’ rea d t he se nte nce al o u d as q uic kl y as y o u ca n wit h o ut ma ki n g err ors.  B ut if 
y o u d o ma ke a n err or, or realize t hat y o u ha ve misse d a w or d, rea d t o t he e n d of t he se nte nce a n d 
t he n g o bac k a n d c orrect y o urself.” 
Sc ori n g: 
T w o pieces of i nf or mati o n are re q uire d t o be rec or de d o n t he sc ore s heet f or eac h test se nte nce:  
t he ti me a n d t he n u m ber of err ors.  Use a st o p watc h t o rec or d t he ti me ta ke n t o rea d eac h 
se nte nce (t o t he nearest 0. 1 sec o n d).  F or eac h se nte nce o n t he sc ore s heet, mar k t he t otal n u m ber 
of w or ds misse d, rea d i nc orrectl y or n ot a ble t o be rea d, a n d t he ti me ta ke n t o rea d t he se nte nce 
(i.e., t he ti me bet wee n w he n y o u sa y ‘start’ a n d w he n t he s u bject fi nis hes utteri n g t he last w or d 
i n t he se nte nce).  Se nte nces t hat c o ul d n ot be rea d or were n ot atte m pte d d ue t o visi o n s h o ul d be 
rec or de d as 0 f or ti me a n d 1 0 f or err ors. 
Meas uri n g Rea di n g F u ncti o n: 
S u bjects’ a vera ge rea di n g s pee d, critical pri nt size, a n d rea di n g ac uit y will be calc ulate d usi n g 
t he data tra nscri be d fr o m t he sc ori n g s heet t o t he electr o nic Case Re p ort F or m a n d will n ot be 
calc ulate d b y t he i nter vie wers. 
Det aile d T a ble f or A d mi nistr ati o n of M N Re a d 
Select e d C o u nt ries 
P ri m ar y L a n g u a ge 
M N Re a d 
U nite d States 
E n glis h, S pa nis h 
X 
U nite d Ki n g d o m 
E n glis h 
X 
Net herla n ds
 D utc h
 
X
St u d y site m ust ma ke best eff ort t o use t he sa me assess or t hr o u g h o ut t he st u d y f or eac h s u bject.  
If a differe nt assess or is use d f or t he sa me s u bject t he rati o nale m ust be clearl y mar ke d i n t he 
s u bject’s st u d y bi n der a n d ma de a vaila ble if re q ueste d. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 6 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x J:  N ati o n al E ye I nstit ute Vis u al F u ncti o ni n g Q uesti o n n ai re 2 5-ite m 
Versi o n ( N EI- V F Q- 2 5) wit h Ne ar a n d Dist a nce Acti vit y S u bsc ale Sc ores 
T he st u d y ce nter a n d I n vesti gat or will i ncl u de t he f oll o wi n g cre dit or attri b uti o n state me nt f or t he 
Nati o nal E ye I nstit ute Vis ual F u ncti o ni n g Q uesti o n naire- 2 5 ( N EI- V F Q- 2 5) q uesti o n naire i n a n y 
p u blic prese ntati o n, p u blicati o n, or ot her disse mi nati o n or refere nce t o t he N EI- V F Q- 2 5 as use d 
i n t his st u d y. 
T he f oll o wi n g f or m, base d u p o n N EI- V F Q- 2 5, was de vel o pe d at R A N D ( htt ps:// w w w.ra n d. or g) 
u n der t he s p o ns ors hi p of t he N EI a n d was a da pte d b y t he S p o ns or f or use i n t his st u d y. 
Si x q uesti o ns fr o m t he a p pe n di x of o pti o nal a d diti o nal q uesti o ns f or t he N EI- V F Q- 2 5, pertai ni n g 
t o t he near a n d dista nce acti vities, were a d de d t o t he f or m.  Mi n or c ha n ges ( n ot affecti n g t he 
ite ms of t he q uesti o n naire) were ma de t o t he f or m, a n d a hea der was a d de d wit h t he st u d y 
n u m ber, S p o ns or’s na me, visit, a n d s u bject i de ntifiers.   
I nstr ucti o ns t o S u bjects: 
“I a m g oi n g t o rea d y o u s o me state me nts a b o ut pr o ble ms, w hic h i n v ol ve y o ur visi o n or feeli n gs 
t hat y o u ha ve a b o ut t he c o n diti o n of y o ur visi o n.  After eac h q uesti o n, I will rea d y o u a list of 
p ossi ble a ns wers.  Please c h o ose t he res p o nse t hat best descri bes y o ur sit uati o n. 
Please a ns wer all t he q uesti o ns as if y o u were weari n g y o ur glasses or c o ntact le nses (if a n y). 
Please ta ke as m uc h ti me as y o u nee d t o a ns wer eac h q uesti o n.  All y o ur a ns wers are 
c o nfi de ntial.  I n or der f or t his st u d y s ur ve y t o i m pr o ve o ur k n o wle d ge a b o ut visi o n pr o ble ms a n d 
h o w t he y affect y o ur q ualit y of life, y o ur a ns wers m ust  be as acc urate as p ossi ble.  Re me m ber, if 
y o u wear glasses or c o ntact le nses f or a partic ular acti vit y, please a ns wer all of t he f oll o wi n g 
q uesti o ns as t h o u g h y o u were weari n g t he m.” 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 7 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 8 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 7 9 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 0 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 1 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 2 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 3 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 4 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 5 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 6 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 7 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L:
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 8 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x K:  Gr a di n g Sc ale f or U veitis 
 
E n d p oi nt
 Gr a de
 
Descri pti o n
 
A nteri or Cells 
0 
< 1 cell i n t he fiel d 
0. 5 + 
1 t o 5 cells i n t he fiel d 
1 + 
6 t o 1 5 cells i n t he fiel d 
2 + 
1 6 t o 2 5 cells i n t he fiel d 
3 + 
2 6 t o 5 0 cells i n t he fiel d 
4 + 
> 5 0 cells i n t he fiel d 
A nteri or Flar e 
0
 N o
 
flar e
 
1 +
 Fai nt
 
2 + 
M o derate, iris a n d le ns details clear 
3 + 
Mar ke d, iris a n d le ns details haz y 
4 + 
I nte nse, fi bri n or plastic a q ue o us 
Vitr e o us Haze 
0 
N o ne, n o cli nical fi n di n gs 
1 
Mi ni mal, p osteri or p ole clearl y visi ble 
2 
Mil d, p osteri or p ole details sli g htl y haz y 
3 
M o der ate, p osteri or p ole details ver y haz y 
4 
Mar ke d, p osteri or p ole details bar el y visi ble 
5 
Se ver e, f u n d us details n ot visi ble 
N ote:  N u m ber of cells see n i n 1 m m x 1 m m hi g h- p o wer e d fiel d. 
 
 

G E M- C L- 1 0 3 1 1 Pr ot oc ol, Versi o n 3. 0  
5 Ma y 2 0 2 1 
Pa ge 8 9 of 8 9 
G E MI NI T H E R A P E U TI C S, I N C.  P R O P RI E T A R Y A N D C O N FI D E N TI A L: 
D O N O T C O P Y O R DI S T RI B U T E WI T H O U T P E R M I S SI O N F R O M G E MI NI T H E R A P E U TI C S, I N C. 
A p pe n di x L:  Me dic ati o ns K n o w n t o P ote nti all y E x acer b ate M ac ul a r E de m a 
or M ac ul ar De ge ner ati o n 
 
M ac ul ar E de m a  
M ac ul ar De ge ner ati o n  
Acetaz ola mi de 
All o p uri n ol 
Al u mi n u m Nic oti nate 
Beta x ol ol 
Br o x y q ui n oli ne 
C h y m otr y psi n 
Dicl or p he na mi de 
Di pi vefri n 
Di pi val yl e pi ne p hri ne ( D P E) 
E pi ne p hri ne 
Et h o xz ola mi de 
Grise of ul vi n 
He xa met h o ni u m 
I n d o met haci n (I n d o metaci n) 
I o di de a n d I o di ne S ol uti o ns a n d C o m p o u n ds 
I o d oc hl or h y dr o x y q ui n 
I o d o q ui n ol ( Dii o d o h y dr o x y q ui n oli ne) 
I ot hala mate Me gl u mi ne a n d/ or S o di u m 
I ot hala mic Aci d 
Le v o b u n ol ol 
Met haz ola mi de 
Na pr o xe n 
Niaci n ( Nic o ntic Aci d) 
Niaci na mi de 
Nic oti n yl Alc o h ol 
P he n yle p hri ne 
Q ui ni ne 
Ra di oacti ve i o di des 
Ta m o xife n (e xcl usi o nar y) 
Ti m ol ol 
All o p uri n ol 
A m o dia q ui n ne 
Br o x y q ui n oli ne 
C hl or o q ui ne 
Cl o ni di ne 
Grise of ul vi n 
H y dr o x yc hl or o q ui ne 
I b u pr ofe n 
I n d o met haci n (I n d o metaci n) 
I o d oc hl or h y dr o x y q ui n 
I o d o q ui n ol 
Q ui ni ne  
S o ur ce:  “ Me dicati o n Ca uti o ns i n  Mac ular De ge ner ati o n. ”  w w w  mac ular. or g/ me dicati o ns- use-ca uti o n.  
Accesse d 0 2 Oct o ber 2 0 1 9.