A Phase 2 Multicenter, Randomized, Double-Masked, Sham-Controlled Study of the Safety and Efficacy of Intravitreal Injections of NGM621 in Subjects With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)
Phase: PHASE2
Conditions: Geographic Atrophy
Sponsor: NGM Biopharmaceuticals, Inc



N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 of 9 6  
I N V E S TI G A T O R P R O T O C O L A P P R O V A L A N D SI G N AT U R E P A G E  
Pr ot oc ol Title  
A P hase 2 M ultice nter, R a n d o mize d, D o u ble- Mas ke d, 
S ha m - C o ntr olle d St u d y of t he Safet y a n d Efficac y of 
I ntr a vitreal I njecti o ns of N G M 6 2 1  i n S u bjects wit h Ge o gra p hic 
Atr o p h y ( G A) Sec o n dar y t o A ge- Relate d Mac ular 
De ge nerati o n ( A M D) ( C A T A LI N A)  
Pr ot oc ol N u m ber  
N G M 6 2 1 -G A - 2 0 1 
N a me of I n vesti g ati o n al 
Pr o d uct  
N G M 6 2 1  
Versi o n #/ D ate of Iss ue 
Versi o n 5. 0 / 1 3 Ma y  2 0 2 1  
 
I N V E S TI G A T O R S T A T E M EN T  
 
I h a ve r ea d t he pr ot oc ol, i ncl u di n g all a p p e n dices, a n d I a gree t hat it c o ntai ns all necessar y 
details f or me a n d m y staff t o c o n d uct t his st u d y as descri be d. I will c o n d uct t his st u d y as 
o utli ne d herei n a n d will ma ke a r eas o na bl e best eff ort t o c o m plete t he st u d y wit hi n t he ti me 
desi g nat e d a n d will i nf or m t he c o m pa n y of a n y d ela ys t hat c o ul d i m pair m y a bilit y t o 
c o m plete t he st u d y.  
I will pr o vi de all st u d y p ers o n nel u n der m y s u p er visi o n c o pies of t he pr ot o c ol a n d access t o 
all i nf or mati o n pr o vi de d b y N G M Bi o p har mace uticals, I nc. I will disc uss t his material wit h 
t he m t o e ns ure t hat t he y are f ull y i nf or m e d a b o ut t he dr u gs a n d t he st u d y. 
 
 
 
 
Pri nci pal I n v esti gat or Na me ( Pri nte d)  
 
Si g nat ure  
 
 
 
Date ( D D M M M Y Y Y Y)  
 
Site N u m ber  
 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 5 of 9 6  
T a ble of C o nte nts  
Title P a ge  ................................................................................................................................................................ 1 
S P O N S O R P R O T O C O L A P P R O V A L A N D SI G N A T U R E P A G E  ...................................................................... 2 
I N V E S TI G A T O R P R O T O C O L A P P R O V A L A N D SI G N A T U R E P A G E .......................................................... 3 
P R O T O C O L C H A N G E HI S T O R Y  ....................................................................................................................... 4 
T a ble of C o nte nts  ................................................................................................................................................... 5 
List of T a bles  ..................................................................................................................................................... 7 
List of A p pe n dices  ............................................................................................................................................. 8 
List of A b bre viati o ns  ......................................................................................................................................... 8 
1  
S y n o psis ....................................................................................................................................................... 1 0  
2  
I ntr o d ucti o n ................................................................................................................................................. 2 8  
2. 1  
B ac k gr o u n d  ..................................................................................................................................... 2 8  
2. 1. 1  
Ge o gra p hic Atr o p h y ( G A)  ....................................................................................................... 2 8  
2. 1. 2  
Mec ha nis m of Acti o n of  N G M 6 2 1  .......................................................................................... 2 8  
2. 1. 3  
T hera pe utic Rati o nale f or N G M 6 2 1 i n Ge o gra p hic Atr o p h y  .................................................. 2 9  
2. 1. 4  
Ge o gra p hic Atr o p h y a n d C urre nt Treat me nts  .......................................................................... 2 9  
2. 2  
S u m mar y of N o ncli nical St u di es  .................................................................................................... 2 9  
2. 3  
S u m mar y of Cli nical St u dies  .......................................................................................................... 3 1  
2. 4  
Rati o nale f or D ose a n d Re gi me n Selecti o n  .................................................................................... 3 4  
3  
St u d y O bj ecti ves a n d E n d p oi nts  .................................................................................................................. 3 5  
3. 1  
Pri mar y O bj ecti ves a n d E n d p oi nts  ................................................................................................. 3 5  
3. 2  
Sec o n dar y O bj ecti ves a n d E n d p oi nts  ............................................................................................. 3 5  
3. 3  
E x pl orat or y O bj ecti ves a n d E n d p oi nts  ........................................................................................... 3 6  
4  
St u d y Desi g n  ............................................................................................................................................... 3 7  
4. 1  
Met h o d ol o g y/ St u d y Desi g n:  .......................................................................................................... 3 7  
4. 2  
St u d y St o p Criteria  ......................................................................................................................... 3 7  
4. 3  
Data Safet y M o nit ori n g B oar d  ........................................................................................................ 3 8  
5  
S u bj ect Selecti o n  ......................................................................................................................................... 3 9  
5. 1  
I ncl usi o n Criteria ............................................................................................................................ 3 9  
5. 2  
E xcl usi o n Criteria  ........................................................................................................................... 4 0  
5. 2. 1  
Oc ular E xcl usi o ns  .................................................................................................................... 4 0  
5. 2. 1. 1  
St u d y E ye  .......................................................................................................................... 4 0  
5. 2. 1. 2  
B ot h E yes  .......................................................................................................................... 4 1  
5. 2. 1. 3  
C o nc urre nt Oc ular C o n diti o ns  ........................................................................................... 4 1  
5. 2. 1. 4  
S yste matic Relate d  ............................................................................................................ 4 2  
5. 3  
C o m paris o n of I ncl usi o n a n d E xcl usi o n Criteria b y St u d y E ye vs. Fell o w  E ye  ............................. 4 2  
5. 4  
Micr o peri metr y ( M P) Criteria ( At Selecte d Sites O nl y)  ................................................................. 4 4  
5. 4. 1  
M P I ncl usi o n Criteria  ............................................................................................................... 4 4  
5. 4. 2  
M P E xcl usi o n Criteria .............................................................................................................. 4 4  
6  
St u d y Treat me nt  .......................................................................................................................................... 4 5  
6. 1  
Cli nical S u p plies  ............................................................................................................................. 4 5  
6. 1. 1  
N G M 6 2 1  .................................................................................................................................. 4 5  
6. 2  
A d mi nistrati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y  ....................................................................... 4 5  
6. 2. 1  
A d mi nistrati o n  ......................................................................................................................... 4 5  
6. 2. 1. 1  
N G M 6 2 1  ............................................................................................................................ 4 5  
6. 2. 1. 2  
S ha m  .................................................................................................................................. 4 5  
6. 2. 2  
St or a ge a n d Sta bilit y  ................................................................................................................ 4 5  
6. 2. 3  
Acc o u nta bilit y  .......................................................................................................................... 4 6  
6. 3  
Ra n d o mizati o n  ................................................................................................................................ 4 6  
6. 3. 1  
Mas ki n g  ................................................................................................................................... 4 6  
6. 3. 2  
Re m o val of St u d y Mas ki n g (If A p plica ble)  ............................................................................. 4 8  
6. 4  
C o nc o mita nt Me dicati o ns  ............................................................................................................... 4 8  

N G M 6 2 1  
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N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 of 9 6  
6. 5  
P er mitte d T hera pies  ........................................................................................................................ 4 9  
6. 6  
Lifest yle C o nsi derati o ns/ Restr icti o ns ............................................................................................. 4 9  
6. 7  
Disc o nti n uati o n of S u bj ects fr o m St u d y P artici pati o n  .................................................................... 4 9  
7  
St u d y Pr oce d ures  ......................................................................................................................................... 5 2  
7. 1  
Sc he d ule of St u d y Pr oce d ures  ........................................................................................................ 5 2  
7. 2  
St u d y Visit Pr oce d ures  ................................................................................................................... 5 8  
7. 2. 1  
Scree ni n g ( Da y – 2 8 t o Da y – 3) Visit  ....................................................................................... 5 8  
7. 2. 2  
B aseli ne ( Da y 1) Treat me nt Visit  ............................................................................................ 5 9  
7. 2. 3  
W ee k 1 ( ± 3 da ys) Visit  ........................................................................................................... 6 0  
7. 2. 4  
W ee k 4 ( ± 5 da ys) Treat me nt Visit  .......................................................................................... 6 0  
7. 2. 5  
W ee k 8 ( ± 5 da ys) Treat me nt Visit  .......................................................................................... 6 1  
7. 2. 6  
W ee k 1 2 ( ± 5 da ys) Treat me nt Visit ( Q 4 W Ar ms O N L Y)  ...................................................... 6 2  
7. 2. 6. 1  
W ee k 1 2 ( ± 5 da ys) T ele p h o ne Safet y Visit ( Q 8 W Ar ms O N L Y)  .................................... 6 2  
7. 2. 7  
W ee k 1 6 ( ± 5 da ys) Treat me nt Visit  ........................................................................................ 6 3  
7. 2. 8  
W ee k 2 0 ( ± 5 da ys) Treat me nt Visit ( Q 4 W Ar ms O N L Y)  ...................................................... 6 3  
7. 2. 8. 1  
W ee k 2 0 ( ± 5 da ys) T ele p h o ne Safet y Visit ( Q 8 W Ar ms O N L Y)  .................................... 6 4  
7. 2. 9  
W ee k 2 4 ( ± 5 da ys) Treat me nt Visit  ........................................................................................ 6 4  
7. 2. 1 0  
W ee k 2 8 ( ± 5 da ys) Treat me nt Visit ( Q 4 W Ar ms O N L Y)  ...................................................... 6 5  
7. 2. 1 0. 1  
W ee k 2 8 ( ± 5 da ys) T ele p h o ne Safet y Visit ( Q 8 W Ar ms O N L Y)  .................................... 6 6  
7. 2. 1 1  
W ee k 3 2 ( ± 5 da ys) Treat me nt Visit  ........................................................................................ 6 6  
7. 2. 1 2  
W ee k 3 6 ( ± 5 da ys) Treat me nt Visit ( Q 4 W Ar ms O N L Y)  ...................................................... 6 7  
7. 2. 1 2. 1  
W ee k 3 6 ( ± 5 da ys) T ele p h o ne Safet y Visit ( Q 8 W Ar ms O N L Y)  .................................... 6 7  
7. 2. 1 3  
W ee k 4 0 ( ± 5 da ys) Treat me nt Visit  ........................................................................................ 6 7  
7. 2. 1 4  
W ee k 4 4 ( ± 5 da ys) Treat me nt Visit ( Q 4 W Ar ms O N L Y)  ...................................................... 6 8  
7. 2. 1 4. 1  
W ee k 4 4 ( ± 5 da ys) T ele p h o ne Safet y Visit ( Q 8 W Ar ms O N L Y)  .................................... 6 8  
7. 2. 1 5  
W ee k 4 8 ( ± 5 da ys) Treat me nt Visit  ........................................................................................ 6 9  
7. 2. 1 6  
W ee k 5 2 ( ± 5 da ys) – E n d of Treat me nt ( E O T) Visit (als o Earl y T er mi nati o n visit f or a n y 
s u bj ects t hat disc o nti n ue bef ore wee k 5 2) ................................................................................................... 6 9  
7. 2. 1 7  
W ee k 5 6 ( ± 5 da ys) – F oll o w u p a n d E n d of St u d y Visit  ........................................................ 7 0  
7. 3  
St u d y Assess me nts a n d E val uati o ns  ............................................................................................... 7 1  
7. 3. 1  
De m o gra p hic/ Oc ular C haract erist ics ...................................................................................... 7 1  
7. 3. 2  
Oc ular/ Me dical a n d S ur gical Hist or y  ...................................................................................... 7 1  
7. 3. 3  
B o d y W ei g ht  ............................................................................................................................ 7 1  
7. 3. 4  
Vital Si g ns  ............................................................................................................................... 7 1  
7. 3. 5  
P h ysical E xa mi nati o n ............................................................................................................... 7 2  
7. 3. 6  
Cli nical La b orat or y E xa mi nati o ns  ........................................................................................... 7 2  
7. 3. 7  
B C V A/ L L V A ........................................................................................................................... 7 3  
7. 3. 8  
Rea di n g S pee d  ......................................................................................................................... 7 4  
7. 3. 8. 1  
T he Mi n nes ota L o w -Visi o n R ea di n g T est ( M N Rea d)  ....................................................... 7 4  
7. 3. 8. 2  
Ra d ner Rea di n g Car ds  ....................................................................................................... 7 4  
7. 3. 9  
F RI I n de x  ................................................................................................................................. 7 4  
7. 3. 1 0  
N EI V F Q -2 5  ............................................................................................................................ 7 4  
7. 3. 1 1  
Slit La m p Bi o micr osc o p y  ........................................................................................................ 7 4  
7. 3. 1 2  
I ntra oc ular Press ure ................................................................................................................. 7 5  
7. 3. 1 2. 1  
P ost I nj ecti o n Assess me nt  ................................................................................................. 7 5  
7. 3. 1 3  
Dilate d F u n d us E xa m a n d I n direct O p ht hal m osc o p y  .............................................................. 7 5  
7. 3. 1 4  
Oc ular I ma gi n g  ........................................................................................................................ 7 6  
7. 3. 1 4. 1  
S D -O C T  ............................................................................................................................. 7 6  
7. 3. 1 4. 2  
F u n d us A ut ofl u oresce nce  .................................................................................................. 7 6  
7. 3. 1 4. 3  
C ol or F u n d us P h ot o gra p h y ( C F P)  ..................................................................................... 7 6  
7. 3. 1 4. 4  
Fl u orescei n A n gi o gra p h y ( F A)  .......................................................................................... 7 7  
7. 3. 1 4. 5  
Micr o peri metr y  .................................................................................................................. 7 7  
7. 3. 1 5  
Ma na ge me nt of C h or oi dal Ne o vasc ularizati o n  ( C N V) ............................................................ 7 7  
7. 3. 1 5. 1  
Ma na ge me nt of C h or oi dal Ne o vasc ularizati o n  ( C N V)-St u d y E ye  .................................... 7 7  
7. 3. 1 5. 2  
Ma na ge me nt of C h or oi dal Ne o vasc ularizati o n  ( C N V)-N o n -St u d y E ye ............................ 7 8  
7. 3. 1 6  
Cli nical Ge n ot y pi n g Sa m ple  .................................................................................................... 7 8  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 of 9 6  
7. 4  
Safet y a n d Ot her Ass ess me nts  ........................................................................................................ 7 9  
7. 4. 1  
A d verse E ve nts  ........................................................................................................................ 7 9  
7. 4. 1. 1  
Defi niti o n of A d verse E ve nts  ............................................................................................ 7 9  
7. 4. 1. 2  
Defi niti o n of Seri o us A d verse E ve nts a n d S A E Re p orti n g  ............................................... 8 0  
7. 4. 1. 3  
Classificati o n of Se verit y of A d verse E ve nt  ...................................................................... 8 1  
7. 4. 1. 4  
Assess me nt of Ca usalit y of A d verse E ve nts  ...................................................................... 8 1  
7. 4. 1. 5  
Pr oce d ures f or Rec or di n g  A d verse E ve nts  ........................................................................ 8 2 
7. 4. 1. 6  
Dia g n osis vers us Si g ns a n d S y m pt o ms  ............................................................................. 8 3  
7. 4. 1. 7  
A d verse E ve nts T hat Are Sec o n dar y t o Ot her E ve nts  ....................................................... 8 3  
7. 4. 1. 8  
Si g ht T hreate ni n g E ve nt  .................................................................................................... 8 4  
8  
Statistical C o nsi derati o ns  ............................................................................................................................ 8 5  
8. 1  
A nal ysis Sets ................................................................................................................................... 8 5  
8. 2  
De m o gra p hics a n d Ot her B aseli ne C haracteristics  ......................................................................... 8 5  
8. 3  
Efficac y A nal yses  ........................................................................................................................... 8 5  
8. 3. 1  
Pri mar y Efficac y A nal yses  ...................................................................................................... 8 6  
8. 3. 1. 1  
Pri mar y Esti ma n d  .............................................................................................................. 8 6  
8. 3. 1. 2  
Mai n Esti mati o n  ................................................................................................................ 8 6  
8. 3. 1. 3  
Se nsiti vit y A nal yses  .......................................................................................................... 8 7  
8. 3. 2  
Sec o n dar y Efficac y A na l yses................................................................................................... 8 7  
8. 4  
Safet y A nal yses  .............................................................................................................................. 8 8  
8. 5  
P har mac o ki netics A nal yses  ............................................................................................................ 8 8  
8. 6  
Sa m ple Size Deter mi nati o n  ............................................................................................................ 8 8  
9  
S u p p orti n g D oc u me ntati o n a n d O perati o nal C o nsi derati o ns  ...................................................................... 9 0  
9. 1  
Re g ulat or y, Et hical, a n d St u d y O versi g ht C o nsi derati o ns  .............................................................. 9 0  
9. 1. 1  
I nf or me d C o nse nt Pr ocess ....................................................................................................... 9 0  
9. 1. 2  
Et hics C o m mittee  ..................................................................................................................... 9 0  
9. 1. 3  
Pr ot oc ol A d here nce  .................................................................................................................. 9 0  
9. 1. 4  
C o nfi de ntialit y a n d Pri vac y ..................................................................................................... 9 0  
9. 1. 5  
Cli nical M o nit ori n g  .................................................................................................................. 9 1  
9. 1. 6  
Q ualit y Ass ura nce a n d Q ualit y C o ntr ol  ................................................................................... 9 1  
9. 1. 7  
Rec or ds  .................................................................................................................................... 9 1  
9. 1. 8  
Fi na nci n g a n d I ns ura nce  .......................................................................................................... 9 2  
9. 1. 9  
P u blicati o n P olic y  .................................................................................................................... 9 2  
1 0  
Refere nces  ................................................................................................................................................... 9 3  
1 0. 1  
List of S p o ns or's Cli nical St u dies Refere nce d i n t his Pr ot oc ol  ....................................................... 9 3  
1 0. 2  
List of S p o ns or's N o ncli nical St u dies Refere nce d i n t his Pr ot oc ol  ................................................. 9 3  
1 0. 3  
Literat ure Refere nces  ...................................................................................................................... 9 3  
1 1  
A p pe n dices  .................................................................................................................................................. 9 5  
1 1. 1  
Gra di n g Scale f or A nteri or C ha m ber Flare or Cells  ....................................................................... 9 5  
1 1. 2  
Gra di n g Scale f or Vitre o us Cells  .................................................................................................... 9 5  
1 1. 3  
Gra di n g Scale f or Vitre o us Ha ze  .................................................................................................... 9 6  
 
List of T a bles  
T a ble  1.  
St u d y 1 8 0 5 0 1: Fre q ue nc y of Treat me nt E mer ge nt A d verse E ve nts ( All  Ca usalities)  ............ 3 2  
T a ble  2.  
St u d y Desi g n St u d y Desi g n  ..................................................................................................... 3 7  
T a ble  3.  
D ose -I nterr u pti o n a n d Treat me nt Disc o nti n uati o n Criteria .................................................... 5 0  
T a ble  4.  
Q 4 W ee k Ar ms Sc he d ule of Assess me nts ( N G M 6 2 1 a n d S h a m)  ............................................ 5 3  
T a ble  5.  
Q 8 W ee k Ar ms Sc he d ule of Assess me nts ( N G M 6 2 1 a n d S ha m)  ............................................ 5 5  
T a ble  6.  
D osi n g Treat me nt Ar ms ( N G M 6 2 1 a n d S ha m)  ....................................................................... 5 7  
T a ble  7.  
Ca usal Attri b uti o n G ui da nce  .................................................................................................... 8 2  
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 of 9 6  
List of A p pe n dices  
A p pe n di x  1.  
Gra di n g Scales  ......................................................................................................................... 9 5  
 
List of A b bre vi ati o ns 
A b bre vi ati o n  Defi niti o n/ E x pl a n ati o n  
A b  
A nti b o d y  
A D A  
A nti -dr u g a nti b o dies  
A D L  
Acti vities of dail y li vi n g  
A M D  
A ge -relate d mac ular de ge nerati o n  
A E  
A d verse e ve nt  
A U C  
Area u n der t he c ur ve  
B C V A  
B est c orrecte d vis ual ac uit y  
C 3  
C o m ple me nt fact or 3/ C o m ple me nt c o m p o ne nt 3  
C F P  
C ol or F u n d us P h ot o gra p h y  
C H 5 0  
C o m ple me nt acti vit y  
C L/ F  
Cleara nce  
C ma x  
Ma xi mal c o nce ntrati o n / Ma xi m u m o bser ve d ser u m c o nce ntrati o n  
C N V  
C h or oi dal ne o vasc ularizati o n  
C R A  
Cli nical researc h ass ociate  
C R C  
Ce ntral rea di n g ce nter  
C R O  
Cli nical researc h or ga nizati o n  
C T C A E  
C o m m o n T er mi n ol o g y Criteri a f or A d verse E ve nts  
D M E  
Dia betic mac ular e de ma  
D S M B  
Data  Safet y M o nit ori n g B oar d  
E C  
Et hics c o m mittee  
e C R F  
Electr o nic case re p ort f or m  
E O S  
E n d of st u d y  
E O T  
E n d of treat me nt  
E R M  
E pireti nal me m bra ne  
E T D R S  
Earl y Treat me nt of Dia betic R eti n o pat h y St u d y  
F A  
Fl u orescei n a n gi o gra p h y  
F A F  
F u n d us a ut ofl u oresce nce  
F RI  
F u ncti o nal rea di n g i n de pe n de nce i n de x  
G A  
Ge o gra p hic Atr o p h y  
HI V  
H u ma n i m m u n o deficie nc y vir us  
I B 
I n vesti gat or’s Br oc h ure  
I C F  
I nf or me d C o nse nt F or m  
I C H 
I nter nati o nal C o nfere nce o n H ar m o nisati o n  
I H R F 
I ntrareti nal h y perreflecti ve f oci  
I O 
I n direct o p ht hal m osc o p y 
I O P 
I ntra oc ular press ure 
I R B 
I nstit uti o nal R e vie w B oar d  
I R T 
I nteracti ve res p o nse tec h n ol o g y  
I V 
I ntra ve n o us 
I V T 
I ntra vitreal 
L L D  
L o w l u mi na nce deficit  
L L T  
L o west le vel ter m  
L L V A  
L o w -l u mi na nce vis ual ac uit y  
M  
Milli o n  
M D  
M ulti ple d ose  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 9 of 9 6  
Me d D R A  
Me dical Dicti o nar y f or Re g ul at or y Acti vities  
mI T T  
M o difie d i nte nt -t o-treat p o p ul ati o n  
M M R M  
Mi xe d -effect m o del f or re peate d meas ures  
M P  
Micr o peri metr y  
M T D  
Ma xi m u m t olerate d d ose  
N EI/ S U N  
Nati o nal e ye i nstit ute/ Sta n dar dizati o n of u veitis n o me nclat ure  
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 naire 2 5 -Ite m 
N G M 6 2 1  
A h u ma nize d I g G 1 m o n ocl o nal a nti b o d y t hat p ote ntl y bi n ds t o h u ma n C 3  
N O A E L  
N o -o bser ve d -a d verse -effect le vel 
S D -O C T  
S pectral D o mai n O ptical c o here nce t o m o gra p h y  
O U  
B ot h e yes  
P D  
P har mac o d y na mic  
PI  
Pri nci pal In vesti gat or  
P K  
P har mac o ki netics  
P P  
P er pr ot oc ol p o p ulati o n  
P R O  
P atie nt re p orte d o utc o me  
Q 4 W  
E ver y 4 wee ks  
Q 8 W  
E ver y 8 wee ks  
R P D  
Retic ular pse u d o dr use n  
R P E  
Reti nal pi g me nt e pit heli u m  
S A D  
Si n gle asce n di n g d ose  
S A E  
Seri o us a d verse e ve nt  
S A P  
Statistical a nal ysis pla n  
S D  
Sta n dar d de viati o n  
S E  
St u d y e ye  
S o A  
Sc he d ule of assess me nts  
T E A E  
Treat me nt e mer ge nt a d verse e ve nt  
t1/ 2 
T er mi nal half -life 
V/ F  
V ol u me of distri b uti o n  
V A  
Vis ual ac uit y  
V E G F  
Vasc ular e n d ot helial gr o wt h fact or  
Y A G  
Yttri u m al u mi n u m gar net  
 
 
 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 1 1  of 9 6  
c. B C V A sc ore as assesse d b y E T D R S c hart at a starti n g dista nce of 
4 meters  
d.  L L V A sc ore as assesse d b y E T D R S c hart at a starti n g dista nce of 
4 meters  
e. L o w L u mi na nce Deficit ( L L D; B C V A – L L V A) i n E T D R S letters at 
a starti n g dista nce of 4 meters  
f. Bi n oc ular rea di n g s pee d b y M N Rea d or Ra d ner rea di n g c harts   
g.  Bi n oc ular critical pri nt si ze as assesse d b y M N Rea d or Ra d ner 
rea di n g c harts  
h.  F u ncti o nal Rea di n g I n de pe n de nce I n de x ( F RI) c o m p osite sc ore  
i. 
N EI V F Q -2 5 c o m p osite sc ore, near acti vit y s u bscale sc ore, dista nce 
acti vit y s u bscale sc ore   
B.  C ha n ge a n d perce nt c ha n ge of s yste mic c o m ple me nt act i vit y ( C H 5 0) 
fr o m baseli ne at eac h visit  
2.  
Sec o n dar y P har mac o ki netics E n d p oi nt:  
A.  Ser u m tr o u g h c o nce ntrati o n of N G M 6 2 1 
3.  
Sec o n dar y I m m u n o ge nicit y E n d p oi nt: 
A.  T he i nci de nce of a nti- N G M 6 2 1 a nti b o dies ( A D As ) i n ser u m 
E x pl or at or y 
O bjecti ve a n d 
E n d p oi nts:  
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 1 2  of 9 6  
I ncl usi o n 
Criteri a  
 
S u bj ects w h o meet t he f oll o wi n g criteria will be i ncl u de d i n t he st u d y:  
1.  Male or fe male ( n o n - pre g na nt, n o n-lactati n g) s u bjects ≥ 5 5 of a ge 
2.  Sta n dar d l u mi na nce B C V A sc ore of 3 4 letters or better usi n g E T D R S c harts 
at t he starti n g dista nce of 4 meters (a p pr o xi matel y 2 0/ 2 0 0 S nelle n e q ui vale nt 
or better ) i n st u d y e ye 
3.  Cli nical dia g n o sis of G A sec o n dar y t o A M D wit h t he G A lesi o n meeti n g t he 
f oll o wi n g criteria as deter mi ne d b y t he ce ntral rea di n g ce nter's assess me nt of 
F u n d us A ut ofl u oresce nce ( F A F) i ma gi n g at scree ni n g: 
a)  T otal G A area m ust be ≥ 2. 5 a n d ≤ 1 7. 5 m m 2  
b)  If G A is m ultifocal, at least o ne f ocal lesi o n m ust be ≥ 1. 2 5 m m 2 
( 0. 5 D A), wit h t he o verall area of G A ≥ 2. 5 a n d ≤ 1 7. 5 m m 2 
c)  T he e ntire G A lesi o n m ust be c o m pletel y vis ualize d o n t he mac ula 
ce ntere d i ma ge a n d m ust be a ble t o be i ma ge d i n its e ntiret y a n d n ot 
c o nti g u ous wit h a n y areas of peri pa pillar y atr o p h y.  
d)   Prese nce of ba n de d or diff use patter n of h y per- a ut ofl u oresce nce i n t he 
j u ncti o nal z o ne of G A. A bse nce of h y per-a ut ofl u oresce nce i n t he j u ncti o nal 
z o ne of t he G A (i.e., patter n = n o ne) is e xcl u de d. 
e)  Well de marcate d G A wit h n o a nat o mical e vi de nce (as assesse d b y F A 
a n d S D-O C T) of c urre nt or pri or C N V i n t he st u d y e ye  
4.  Clear oc ular me dia a n d a de q uate p u pil dilatati o n a n d fi xati o n i n b ot h e yes t o 
per mit g o o d q ualit y p h ot o gra p hic i ma gi n g 
5.  Fe male s u bjects m ust be eit her of a) n o n-c hil d beari n g p ote ntial, defi ne d as 
w o me n w h o ha ve ha d a h ysterect o m y, bilateral o o p h orect o m y, me dicall y 
d oc u me nte d o varia n fail ure, d oc u me nte d p ost me n o pa usal, or a f ollicle 
sti m ulati n g h or m o ne > 4 0 mI U/ m L, or b) if of c hil d beari n g p ote ntial, 
defi ne d as w o me n wit h < 2 years of a me n orr hea (a bse nce of me nstr uati o n), 
t he n m ust ha ve a ne gati ve ser u m pre g na nc y test at Scree ni n g a n d uri ne 
pre g na nc y test at t he Da y 1 visit pri or t o first d ose of st u d y dr u g.  
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 1 3  of 9 6  
6.  Fe male s u bjects of c hil d beari n g p ote ntial  a n d male s u bjects wit h a fe male 
part ner of c hil d beari n g p ote ntial m ust eit her be a bsti ne nt or be usi n g 
c o nsiste nt a n d a de q uate birt h c o ntr ol fr o m Scree ni n g t o E n d of St u d y ( E O S / 
Wee k 5 6). O ne of t he f oll o wi n g f or ms of c o ntrace pti o n is re q uire d:  
a)   C o n do m  
b)   H or m o ne- c o ntai ni n g c o ntrace pti ve  
c)  I ntra uteri ne de vice wit h a fail ure rate < 1 % per year  
d)  Cer vical ca p or dia p hra g m wit h s per mici dal a ge nt  
e)  T u bal sterilizati o n  
f)  Vasect o m y i n male part ner  
7.  Willi n g a n d a ble t o gi ve i nf or me d c o nse nt, writte n l ocal pri vac y 
re q uire me nts, c o m pl y wit h all visit pr oce d ures a n d li kel y t o c o m plete t he 
st u d y 
E xcl usi o n 
criteri a 
Oc ul ar E xcl usi o ns  
St u d y E ye  
•  
Hist or y of pri or i ntra vitreal i njecti o n  f or ne o vasc ular A M D (see e xce pti o n 
bel o w), vitrect o m y s ur ger y, s u b mac ular s ur ger y, or a n y s ur gical i nter ve nti o n 
f or A M D. A si n gle i ntra vitreal i njecti o n of a nti- V E G F, if a d mi nistere d 
> 2 years pri or t o scree ni n g, is per mitte d . A si n gle i ntra o perati ve 
a d mi nistrati o n of a c ortic oster oi d d uri n g cataract s ur ger y f or c yst oi d mac ular 
e de ma pr o p h yla xis at least 3 m o nt hs pri or t o scree ni n g is per mitte d. 
•  
G A sec o n dar y t o a c o n diti o n ot her t ha n A M D i n eit her e ye 
(e. g., m o n o ge netic mac ular d ystr o p hies li ke Star gar dt disease, c o ne r o d 
d ystr o p h y, t o xic mac ul o pat hies) 
•  
A n y hist or y of or acti ve c h or oi dal ne o vasc ularizati o n ( C N V), base d o n 
fl u orescei n a n gi o gra p h y ( F A) a n d S D-O C T i ma gi n g as assesse d b y t he 
Ce ntral Rea di n g Ce nter  
•  
Pre vi o us laser p h ot oc oa g ulati o n f or C N V, dia betic mac ular e de ma ( D M E), 
reti nal vei n occl usi o n a n d pr oliferati ve dia betic reti n o pat h y 
•  
I ntra oc ular s ur ger y (i ncl u di n g le ns re place me nt s ur ger y) wit hi n 3 m o nt hs 
pri or t o ra n d o mizati o n 
•  
Hist or y of laser t hera p y i n t he mac ular re gi o n  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 1 4  of 9 6  
•  
A p ha kia or a bse nce of t he p osteri or ca ps ule. N ote: yttri u m al u mi n u m gar net 
( Y A G) laser p osteri or ca ps ul ot o m y f or p osteri or ca ps ule o pacificati o n d o ne 
at least 6 0 da ys pri or t o scree ni n g is n ot e xcl u de d. 
•  
A n y oc ular c o n diti o n ot her t ha n G A sec o n dar y t o A M D t hat ma y re q uire 
s ur ger y or me dical i nter ve nti o n (i ncl u di n g le ns re place me nt s ur ger y) d uri n g 
t he st u d y peri o d or, i n t he o pi ni o n of t he I n vesti gat or, c o ul d c o m pr o mise 
vis ual f u ncti o n d uri n g t he st u d y peri o d. 
•  
A n y c o ntrai n dicati o n t o I V T i njecti o n i ncl u d i n g c urre nt oc ular or peri oc ular 
i nfecti o n 
•  
A ut oi m m u ne u veitis or scleritis, or c hr o nic i nfla m mat or y disease of a nteri or 
se g me nt, i ncl u di n g c hr o nic kerat oc o nj u ncti vitis sicca ( m ore t ha n mil d) or 
i nfla m mat or y ble p haritis ( n o ni nfecti o us) of eit her e ye ( greater t ha n mil d 
se verit y), or c hr o nic i nfla m mat or y disease of p osteri or c ha m ber  
Fell o w ( N o n-st u d y) E ye  
•  
A n y hist or y of or acti ve C N V less t ha n 2 years i n d urati o n. C N V of greater 
t ha n 2 years si nce cli nical dia g n osis is per mitte d f or u p t o 2 5 % of t he t otal 
patie nt p o p ulati o n. Per mitte d C N V ca n be recei vi n g acti ve treat me nt (e. g. 
a nti-V E G F).  
B ot h E yes 
•  
A n y hist or y of or acti ve bacterial, viral, f u n gal, or parasitic i nfecti o n i n 
eit her e ye i n t he 3 m o nt hs pri or t o ra n d o mizati o n   
•  
Rece i ve d a n y reti nal ste m cell treat me nt  
•  
Pre vi o us partici pati o n i n i nter ve nti o nal cli nical trials f or G A or dr y A M D, 
re gar dless of t he r o ute of a d mi nistrati o n (i.e., oc ular or s yste mic) wit hi n t he 
last 6 m o nt hs of Da y 1. Pri or partici pati o n i n vita mi n a n d mi neral cli nical 
trials is all o we d at a n y ti me pri or t o Da y 1.   
•  
Patie nts t hat recei ve d pe gcetac o pla n (als o k n o w n as A P L -2; A pellis) or 
a vaci nca pta d pe g ol (als o k n o w n as Zi m ura; I veric Bi o, f or merl y 
O p ht h otec h) i n eit her e ye are n ot eli gi ble f or partici pati o n . 
C o nc urre nt Oc ul ar C o n diti o ns  
•  
Reti nal pi g me nt e pit heli u m ( R P E) tear t hat i n v ol ves t he mac ula i n eit her e ye  
•  
Prese nce of a n acti ve oc ular disease i n eit her or b ot h e yes t hat i n t he o pi ni o n 
of t he I n vesti gat or c o m pr o mises or c o nf o u n ds vis ual f u ncti o n, i ncl u di n g b ut 
n ot li mite d t o, u veitis, ot her mac ular diseases (e. g., cli nicall y si g nifica nt 
e pireti nal me m bra ne [ ER M ], f ull t hic k ness mac ular h ole or u nc o ntr olle d 
gla uc o ma/ oc ular h y perte nsi o n ). 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 1 5  of 9 6  
•  
Hist or y of i di o pat hic or a ut oi m m u ne -ass ociate d u veitis i n eit her e ye  
•  
Acti ve, i nfecti o us c o nj u ncti vitis, keratitis, scleritis, or e n d o p ht hal mitis i n 
eit her e ye  
•  
S p herical e q ui vale nt of t he refracti ve err or i n t he st u d y e ye de m o nstrati n g 
> 8 di o pters of m y o pia ( deter mi ne a xial le n gt h, e xcl u de if a xial le n gt h 
> 2 6 m m)  
•  
Pr oliferati ve dia betic reti n o pat h y or dia betic mac ular e de ma i n eit her e ye  
•  
Hist or y of rec urre nt i nfecti o us or  i nfla m mat or y oc ular disease i n eit her e ye. 
N ote: s u bjects wit h mil d ble p haritis will be all o we d.  
S yste m atic R el ate d  
•  
Cli nicall y si g nifica nt me dical or ps yc hiatric c o n diti o ns t hat, i n t he o pi ni o n of 
t he In vesti gat or, ma ke c o nsiste nt f oll o w - u p o ver t he 1 2-m o nt h treat me nt 
peri o d u nli kel y, or w o ul d ma ke t he s u bject a n u nsafe st u d y ca n di date. 
•  
A n y scree ni n g la b orat or y val ue ( he mat ol o g y, ser u m c he mistr y or uri nal ysis) 
t hat i n t he o pi ni o n of t he I n vesti gat or is cli nicall y si g nifica nt a n d n ot s uita ble 
f or st u d y partici pati o n 
•  
Prese nce or treat me nt f or a n y acti ve s yste mic or l ocalize d i nfecti o n    
•  
K n o w n aller g y t o c o nstit ue nts of t he st u d y dr u g f or m ulati o n or cli nicall y 
rele va nt se nsiti vit y t o fl u orescei n 
•  
K n o w n si g nifica nt hist or y of dr u g/alc o h ol a b use or a p ositi ve dr u gs of a b use 
test at scree ni n g t hat c o ul d n ot be e x plai ne d as a p pr o priate ma na ge me nt of a 
me dical c o n diti o n. ( Ca n na bi n oi ds are n ot part of dr u g scree n) 
•  
Hist or y se vere aller gic or a na p h ylactic reacti o ns t o rec o m bi na nt t hera pe utic 
pr otei ns, f usi o n pr otei ns, or c hi meric, h u ma n, or h u ma nize d a nti b o dies  
•  
Hist or y of mali g na nc y dia g n ose d or treate d wit hi n 2 years (rece nt l ocalize d 
treat me nt of s q ua m o us or n o n-i n vasi ve basal cell s ki n ca ncers is per mitte d; 
cer vical carci n o ma i n sit u or breast d uct ular carci n o ma i n sit u is all o we d if 
a p pr o priatel y treate d wit hi n 2 years pri or t o Scree ni n g); s u bjects u n der 
e val uati o n f or mali g na nc y are n ot eli gi ble.  
Micr o peri met r y ( M P) Criteri a ( At Selecte d Sites O nl y)  
M P I ncl usi o n Criteri a  
Micr o peri metr y  scree ni n g test criteria f or eli gi bilit y: 
•  
M ust be a ble t o detect fi xati o n tar get 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 1 6  of 9 6  
•  
T otal ela pse d ti me t o c o m plete t he 1 0 - 2 6 8-p oi nt e xa m is ≤ 3 0 mi n utes i n 
d urati o n 
•  
Relia bilit y T est rati o ≤ 2 0 % (false p ositi ve rate)  
•  
A bilit y a n d willi n g ness t o u n derta ke M P as sess me nt as deter mi ne d b y 
I n vesti gat or 
M P E x cl usi o n Criteri a  
•  
I n vesti gat or deter mi nes t hat s u bject is u na ble t o perf or m t he rest relia bl y. 
N ote: dis q ualificati o n fr o m t he micr o peri metr y assess me nt d oes n ot e xcl u de 
a s u bject fr o m t he trial partici pati o n if s he/ he q ualifies as per t he rest of t he 
st u d y e ntr y criteria. 
C o m p aris o n 
of I ncl usi o n 
a n d E xcl usi o n 
Criteri a b y 
St u d y E ye vs. 
F ell o w E ye  
Criteri o n  
St u d y 
E ye  
Fell o w 
E ye  
I ncl usi o n Criteri a / Oc ul ar C o n diti o ns: 
 
 
•  
Sta n dar d l u mi na nce B C V A sc ore of 3 4 letters or better 
usi n g E T D R S c harts at t he  starti n g dista nce of 4 meters 
(a p pr o xi matel y 2 0/ 2 0 0 S nelle n e q ui vale nt or better ) i n 
t he st u d y e ye 
 
 
•  
Cli nical dia g n osis of G A sec o n dar y t o A M D wit h t he 
G A lesi o n meeti n g t he f oll o wi n g criteria as deter mi ne d 
b y t he ce ntral rea di n g ce nter's assess me nt of F u n d us 
A ut ofl u oresce nce ( F A F) i ma gi n g at scree ni n g:  
 
a)      T otal G A area m ust be ≥ 2. 5 a n d ≤ 1 7. 5 m m 2 
b)      If G A is m ultif ocal, at least o ne f ocal lesi o n m ust be 
≥ 1. 2 5 m m 2 ( 0. 5 D A), wit h t he o verall area of G A 
≥ 2. 5 a n d ≤ 1 7. 5 m m 2 
c)      T he e ntire G A lesi o n m ust be c o m pletel y vis ualize d 
o n t he mac ula ce ntere d i ma ge a n d m ust be a ble t o be 
i ma ge d i n its e ntiret y a n d n ot c o nti g u o us wit h a n y areas 
of peri pa pillar y atr o p h y  
d)      Prese nce of ba n de d or diff use patter n of 
h y per -a ut ofl u oresce nce i n t he j u ncti o nal z o ne of G A. 
A bse nce of h y per -a ut ofl u oresce nce i n t he j u ncti o nal 
z o ne of t he G A (i.e., patter n = n o ne ) is e xcl u de d 
e) W ell de marcate d G A wit h n o a nat o mical e vi de nce (as 
assesse d b y F A a n d S D O C T) of c urre nt or pri or C N V  
 
 
•  
Clear oc ular me dia a n d a de q uate p u pil dilatati o n a n d 
fi xati o n t o per mit g o o d q ualit y p h ot o gra p hic i ma gi n g. 
 
 
E xcl usi o n Criteri a  / Oc ul ar C o n diti o ns 
 
 
•  
Hist or y of pri or i ntra vitreal i njecti o n f or 
ne o vasc ular A M D (see e xce pti o n bel o w) ; a si n gle 
i ntra vitreal i nj ecti o n of a nti-V E G F, if a d mi nistere d 
> 2 years pri or t o scree ni n g, is per mitte d. A si n gle 
i ntra o perati ve a d mi nistrati o n of a c ortic oster oi d d uri n g 
cataract s ur ger y f or c yst oi d mac ular e de ma pr o p h yla xis 
at least 3 m o nt hs pri or t o scree ni n g is per mitte d.  
 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 1 7  of 9 6  
•  
G A sec o n dar y t o a c o n diti o n ot her t ha n A M D i n eit her 
e ye (e. g.,  m o n o ge netic mac ular d ystr o p hies li ke 
Star gar dt disease, c o ne r o d d ystr o p h y, t o xic 
mac ul o pat hies).  
 
 
•  
A n y hist or y of or acti ve c h or oi dal ne o vasc ularizati o n 
( C N V), base d o n fl u orescei n a n gi o gra p h y ( F A) a n d 
S D -O C T i ma gi n g as assesse d  b y t he Ce ntral Rea di n g 
Ce nter  
 
 
•  
Pre vi o us laser p h ot oc oa g ulati o n f or C N V, dia betic 
mac ular e de ma ( D M E), reti nal vei n occl usi o n , a n d 
pr oliferati ve dia betic reti n o pat h y.  
 
 
•  
I ntra oc ular s ur ger y (i ncl u di n g le ns re place me nt s ur ger y) 
wit hi n 3 m o nt hs pri or t o ra n d o mizati o n. 
 
 
•  
Hist or y of laser t hera p y i n t he mac ular re gi o n.  
 
 
•  
A p ha kia or a bse nce of t he p osteri or ca ps ule. N ote: 
yttri u m al u mi n u m gar net ( Y A G) laser p osteri or 
ca ps ul ot o m y f or p osteri or ca ps ule o pacificati o n d o ne at 
least 6 0 da ys pri or t o scree ni n g is n ot e xcl u de d. 
 
 
•  
A n y oc ular c o n diti o n ot her t ha n G A sec o n dar y t o A M D 
t hat ma y re q uire s ur ger y or me dical i nter ve nti o n 
(i ncl u di n g le ns re place me nt s ur ger y) d uri n g t he st u d y 
pe ri o d or, i n t he o pi ni o n of t he I n vesti gat or, c o ul d 
c o m pr o mise vis ual f u ncti o n d uri n g t he st u d y peri o d.  
 
 
•  
A n y c o ntrai n dicati o n t o I V T i nj ecti o n i ncl u di n g c urre nt 
oc ular or peri oc ular i nfecti o n.  
 
 
•  
A ut oi m m u ne u veitis or scleritis, or c hr o nic i nfla m mat or y 
disease of a nteri or se g me nt, i ncl u di n g c hr o nic 
kerat oc o nj u ncti vitis sicca ( m ore t ha n mil d) or 
i nfla m mat or y ble p haritis ( n o ni nfecti o us) of eit her e ye 
( greater t ha n mil d se verit y), or c hr o nic i nfla m mat or y 
disease of p osteri or c ha m be r. 
 
 
•  
A n y hist or y of or acti ve C N V < 2 years i n d urati o n. 
C N V of > 2 years si nce cli nic al dia g n osis is per mitte d 
f or u p t o 2 5 % of t he t otal patie nt p o p ulati o n. P er mitte d 
C N V ca n be recei vi n g acti ve treat me nt (e. g., 
a nti -V E G F).  
 
 
•  
A n y hist or y of or acti ve bacterial, viral, f u n gal, or 
parasitic i nfecti o n i n t he 3 m o nt hs pri or t o ra n d o mizati o n  
 
 
•  
Recei ve d a n y reti nal ste m cell treat me nt.  
 
 
•  
Pre vi o us partici pati o n i n i nter ve nti o nal cli nical trials f or 
G A or dr y A M D,  re gar dless of t he r o ute of 
a d mi nistrati o n (i.e., oc ular or s yste mic) wit hi n t he last 
6 m o nt hs of Da y 1. Pri or partici pati o n i n vita mi n a n d 
mi neral cli nical trials is all o we d at a n y ti me pri or t o 
Da y  1.   
 
 
 
•  
P atie nts t hat recei ve d pe gceta c o pla n (als o k n o w n as 
A P L 2; A pellis) or a vaci nca pta d pe g ol (als o k n o w n as 
Zi m ura; I veric Bi o, f or merl y O p ht h otec h) i n eit her e ye 
are n ot eli gi ble f or partici pati o n.  
 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 1 8  of 9 6  
E xcl usi o n C riteri a / C o nc urre nt O c ul ar C o n diti o ns:  
 
 
•  
Reti nal pi g me nt e pit heli u m ( R P E) tear t hat i n v ol ves t he 
mac ula  
 
 
•  
Prese nce of a n acti ve oc ular disease t hat i n t he o pi ni o n 
of t he I n vesti gat or c o m pr o mis es or c o nf o u n ds vis ual 
f u ncti o n, i ncl u di n g b ut n ot li mite d t o, u veitis, ot her 
mac ular diseases (e. g., cli nicall y si g nifica nt e pireti nal  
me m bra ne ( E R M), f ull t hic k ness mac ular h ole or 
u nc o ntr olle d gla uc o ma/ oc ular h y perte nsi o n ). 
 
 
•  
Hist or y of i di o pat hic or a ut oi m m u ne -ass ociate d u veitis  
 
 
•  
Acti ve, i nfecti o us c o nj u ncti vitis, keratitis, scleritis, or 
e n d o p ht hal mitis  
 
 
•  
S p herical e q ui vale nt of t he refracti ve err or i n t he st u d y 
e ye de m o nstrati n g > 8 di o pters of m y o pia ( deter mi ne 
a xial le n gt h, e xcl u de if a xial l e n gt h > 2 6 m m).  
 
 
•  
Pr oliferati ve dia betic reti n o pat h y or dia betic mac ular 
e de ma  
 
 
•  
Hist or y of rec urre nt i nfecti o us or i nfl a m mat or y oc ular 
disease. N ote:  s u bj ects wit h mil d ble p haritis will be 
all o we d.  
 
 
 
St u d y Desi g n/  
Met h o d ol o g y:  
T his is a P hase 2 ra n d o mize d, d o u ble- mas ke d, s ha m -c o ntr olle d, m ultice nter 
st u d y of t he safet y a n d efficac y of i ntra vitreal i njecti o ns of N G M 6 2 1  i n s u bjects 
wit h G A sec o n dar y t o A M D i n o ne or b ot h e yes. O nl y o ne e ye ca n be c h ose n as 
t he st u d y e ye. I n t he e ve nt b ot h e yes are eli gi ble, t he e ye wit h t he w orse vis ual 
f u ncti o n (l o wer B C V A val ue) will be c o nsi dere d f or t he p ur p ose of t his st u d y as 
t he st u d y e ye. If b ot h e yes ha ve t he sa me vis ual f u ncti o n, t he e ye wit h t he lar ger 
area of G A will be selecte d as t he st u d y e ye. I n t he e ve nt t hat b ot h e yes ha ve t he 
sa me vis ual f u ncti o n a n d G A area, t he ri g ht e ye will be selecte d. 
A p pr o xi matel y 3 1 8 s u bjects, scree ne d wit hi n 4 wee ks pri or t o d osi n g, w h o ha ve 
si g ne d t he i nf or me d c o nse nt a n d meet all eli gi bilit y criteria, will be assi g ne d 
ra n d o ml y t o 1 of 4 treat me nt gr o u ps i n a rati o of 2: 1: 2: 1 t o recei ve I V T 
i njecti o ns of 1 5 m g of N G M 6 2 1 ( 1 0 0 µ L v ol ume) or S ha m, e ver y 4 wee ks or 
e ver y 8 wee ks f or a t otal of 5 2 wee ks (see St u d y D esi g n ta ble  bel o w a n d 
pr ot oc ol  T a ble  6). S u bjects will be m o nit ore d f or 5 6 wee ks, a n d t he t otal 
d urati o n of i n di vi d ual partici pati o n (i ncl u di n g scree ni n g ti me) will be 
a p pr o xi matel y 6 0 wee ks. S u bj ects w h o disc o nti n ue bef ore c o m pleti o n of 
5 2 wee ks of  treat me nt ma y be re place d. Mes o pic micr o peri metr y of t he st u d y 
e ye o nl y will be perf or me d at select st u d y sites. F or a d diti o nal details please 
refer t o Secti o n  7. 3. 1 4. 5  of t he pr ot oc ol.  
 
 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 2 0  of 9 6  
Sc he d ule of 
Assess me nts / 
Q 4 Wee k 
Ar ms 
( N G M 6 2 1 a n d 
S h a m)  
St u dy fl o wc h art f or Q 4 W Ar ms: D ay 1, Week 1, Week 4 t hr o u g h Week 5 6  
Acti vit y/  
Assess me nt  
Scree n  B aseli ne  
Tre at me nt  
 
F oll o w 
U p  
D a y -2 8 
t o 
D a y  -3  D a y 1  
W k 
1  W k 4  W k 8  
W k 
1 2  
W k 
1 6  
W k 
2 0  
W k 
2 4  
W k 
2 8  
W k 
3 2  
W k 
3 6  
W k 
4 0  
W k 
4 4  
W k 
4 8  
W k 5 2  
E O T  [ 9] 
W k 5 6  
E O S  
M o nt h  
 
 
 
M 1  M 2  M 3  M 4  M 5  M 6  M 7  M 8  M 9  M 1 0  M 1 1  M 1 2  
M 1 3  
M 1 4  
Visit  Wi n d o ws  
 
 
± 3  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
I nf or me d C o nse nt  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I ncl usi o n/ 
E xcl usi o n 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
De m o gra p h ics 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
Oc ular/ Me dical  
Hist or y  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P h ysical  E xa m  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
B o d y Wei g ht  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
Pre g na nc y  T esti n g [ 1] 
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
Bl o o d Sa m ple 
( He mat ol o g y, 
c he mistr y) [ 2] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Uri ne Sa m ple 
( Uri nal ysis, 
Dr u g Scree n)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A d verse  E ve nts  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C o nc o mita nt  
Me dicati o ns  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital  Si g ns  
X  
 
 
 
 
 
 
 
X  
 
 
 
 
 
 
X  
X  
F RI I n de x  [3 ] 
 
X  
 
 
 
 
 
 
X  
 
 
 
 
 
 
X  
 
N EI V F Q -2 5 [ 3] 
 
X  
 
 
 
 
 
 
X  
 
 
 
 
 
 
X  
 
B C V A  
O U  
O U  
O U  O U  O U  O U  
O U  O U  
O U  O U  O U  O U  O U  O U  O U  
O U  
O U  
L L V A  
O U  
 
 
 
 
 
 
 
O U  
 
 
 
 
 
 
O U  
 
Rea di n g S pee d  
 
X  
 
 
 
 
 
 
X  
 
 
 
 
 
 
X  
 
Pre - a n d P ost-d ose 
I O P [ 4] 
O U  
O U  
S E  
S E  
S E  
O U  
S E  
S E  
O U  
S E  
S E  
O U  
S E  
S E  
S E  
O U  
O U  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 2 1  of 9 6  
Slit la m p  
Bi o micr osc o p y  
O U  
O U  
O U  O U  O U  O U  O U  O U  O U  O U  O U  O U  O U  O U  O U  
O U  
O U  
Dilate d F u n d us E xa m 
a n d I n direct 
O p ht hal m osc o p y  
O U  
O U  
O U  O U  O U  O U  O U  O U  O U  O U  O U  O U  O U  O U  O U  
O U  
O U  
S D -O C T  [ 5] 
O U  
 
 
 
 
 
O U  
 
O U  
 
O U  
 
O U  
 
 
O U  
O U  
F u n d us 
A ut ofl u oresce nce 
( F A F) [ 6] 
O U  
 
 
 
 
 
 
 
O U  
 
 
 
 
 
 
 O U  
 
Fl u orescei n 
a n gi o gra p h y ( F A)  [ 5] 
O U  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C ol or F u n d us 
P h ot o gra p h y ( C F P)  
O U  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
O U  
 
Micr o peri metr y at 
select sites ( St u d y e ye 
o nl y) [ 7] 
S E  
S E  
 
 
 
 
 
 
S E  
 
 
 
 
 
 
S E  
 
Ser u m P K [ 8] 
 
X  
X  
X  
 
 
X  
 
X  
 
 
 
X  
 
X  
X  
X  
Ser u m  A D A [8] 
 
X  
  
X  
 
 
X  
 
X  
 
 
 
X  
 
X  
X  
X  
Ser u m N A b [ 8] 
 
X  
 
X  
 
 
X  
 
X  
 
 
 
X  
 
X  
X  
X  
Ser u m  –  C3 a nd C H 5 0  
 
X  
X  
X  
 
 
 
 
X  
 
 
 
 
 
 
X  
X  
Ra n d o mizati o n  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
O pti o nal B uccal S wa b 
f or ge netic testi n g[ 1 0] 
 
O ne -ti me c ollecti o n at a ny visit fr o m D ay 1 t o E O S. C ollect o nly if s u bject h as c o nse nte d t o o pti o n al 
pr oce d ure . 
D osi n g ( Please see  T a ble  6 ) 
O U  = b ot h  e yes; S E  = st u d y e ye; X = Re q uire d  
[ 1] Fe males of c hil d beari n g p ote ntial o nl y; Ser u m pre g na nc y test t o be c o n d ucte d at scree ni n g. Uri ne pre g na nc y test t o be c o n d uct e d o n 
Da y  1 a n d W ee k 4 8 visit. If pre g na nc y is s us pecte d, a ser u m pre g na nc y test ma y be c o n d ucte d.  
[ 2] F or t he scree ni n g visit o nl y, it is all o wa ble t o dra w bl o o d i n t he or der of assess me nts as liste d i n t he ta ble O R t he bl o o d d ra w ca n occ ur 
ri g ht bef ore t he F A assess me nt t o all o w f or a si n gle nee dle stic k.  
[ 3] T he patie nt -re p orte d o utc o me ( P R O) meas ures ( N EI V F Q-2 5 a n d F RI I n de x) will be a d mi nistere d b y t he mas ke d sit e staff (e xce pt f or 
t he V A e xa mi ner) pri or t o a n y ot her visit assess me nts bei n g perf or me d. 
[ 4] Refere nce Secti o n  7. 3. 1 2. 1  a n d t he p har mac y ma n ual f or details.  
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 2 4  of 9 6 
O pti o nal B uccal 
S wa b f or ge netic 
testi n g[ 1 1] 
 
O ne -ti me c ollecti o n at a ny visit fr o m D ay 1 t o E O S. C ollect o nly if s u bject h as c o nse nte d t o o pti o n al 
pr oce d ure . 
D osi n g  ( please see T a ble  6 ) 
O U  = b ot h  e yes; S E  = st u d y e ye; X = Re q uire d  
[ 1] Fe males of c hil d beari n g p ote ntial o nl y; Ser u m pre g na nc y test t o be c o n d ucte d  at scree ni n g. Uri ne pre g na nc y test t o be c o n d ucte d o n 
Da y  1 a n d W ee k 4 8 visit. If pre g na nc y is s us pecte d, a ser u m pre g na nc y test ma y be c o n d ucte d.  
[ 2] F or t he scree ni n g visit o nl y, it is all o wa ble t o dra w bl o o d i n t he or der of assess me nts as liste d i n t h e ta ble O R t he bl o o d dra w ca n occ ur 
ri g ht bef ore t he F A assess me nt t o all o w f or a si n gle nee dle stic k.  
[ 3] C ol u m ns s ha de d gra y i n dic ate t hat a d verse e ve nt re p orti n g will be b y tele p h o ne ( 
) f or n o n-visit m o nt hs ( W ee ks 1 2, 2 0, 2 8, 3 6, a n d 
4 4) f or s u bj ects  i n t he Q 8 W ar m o nl y. 
[ 4] T he patie nt -re p orte d o utc o me ( P R O) meas ures ( N EI V F Q-2 5 a n d F RI I n de x) will be a d mi nistere d b y t he mas ke d sit e staff (e xce pt f or 
t he V A e xa mi ner) pri or t o a n y ot her visit assess me nts bei n g perf or me d. 
[ 5] Refere nce Secti o n  7. 3. 1 2. 1  a n d t he p har mac y ma n ual f or details.  
[ 6] A F A a n d S D -O C T s h o ul d be perf or me d if t he de vel o p me nt of C N V is s us pecte d i n st u d y e ye.  T he ce ntral rea di n g c e nter m ust c o nfir m 
t his fi n di n g bef ore a n y i nter ve nti o n is i nitiate d. See Secti o n  7. 3. 1 5  f or details. 
[ 7] After ra n d o mizati o n, if a patie nt misses a st u d y visit w he n F A F i ma ges were sc he d ule d t o be ta ke n, t he i ma ges s h o ul d be ta ke n  at t he 
ne xt sc he d ule d visit.  
[ 8]   Micr o peri metr y is o pti o nal a n d a p plies t o select sites.  
[ 9] P K, A nti -dr u g a nti b o d y a n d ne utralizi n g a nti b o d y sa m ples will be c ollecte d Da y 1 pre -d ose , W ee k 1  p ost -d ose  ( P K c ollecti o n o nl y), 
W ee k 4 p ost -d ose , W ee k s 8, 1 6, 2 4, 4 0, 4 8  pre -d ose , a n d W ee ks 5 2 a n d 5 6 . 
[ 1 0] F or s u bj ects w h o disc o nti n ue earl y fr o m t he st u d y, t he E O T visit assess me nt s s h o ul d be perf or me d after a mi ni m u m of 2 8 da ys has 
ela pse d fr o m t he last a d mi nist ere d d ose. See Secti o n  6. 7  f or details. 
[ 1 1] F or  s u bj ects w h o c o nse nte d t o t he o pti o nal sa m ple c ollecti o n. 
Sc he d ule of 
Assess me nts / 
D osi n g 
Tre at me nt 
Ar ms  
Tre at me nt Ar m  
Scree n  B aseli ne  
Tre at me nt  
 
F oll o w 
U p  
D a y -2 8 
t o 
D a y -3  
D a y 1  
W k 
1  
W k 
4  
W k 
8  
W k 
1 2  
W k 
1 6  
W k 
2 0  
W k 
2 4  
W k 
2 8  
W k 
3 2  
W k 
3 6  
W k 
4 0  
W k 
4 4  
W k 
4 8  
W k 5 2  
E O T  
 
W k 5 6  
E O S  
N G M 6 2 1 1 5 m g Q 4 W  
 
X [ 1] 
 
X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] 
  
 
S ha m Q 4 W  
 
X [ 1] 
 
X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] X [ 1] 
 
 
N G M 6 2 1 1 5 m g Q 8 W  
 
X [ 1] 
 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
 
S ha m Q 8 W  
 
X [ 1] 
 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
 
[ 1] Refer t o Secti o n  7. 3. 1 2. 1  a n d  t he p harmac y ma n ual  f or details o n treat me nt a d mi nistrati o n a n d pre- a n d p ost-d ose I O P m o nit ori n g, a n d if 
nee de d, I O P ma na ge me nt i nstr ucti o ns.  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 2 5  of 9 6  
 
St atistic al 
Met h o ds  
A n al ysis Sets  
•  
M o difie d I nte nt- T o -Treat ( mI T T) A nal ysis Set: All ra n d o mize d a n d treate d 
( wit h at least o ne d ose of st u d y dr u g) s u bjects. T his a nal ysis set will be use d 
f or all efficac y a nal yses a n d s u bjects will be a nal yze d base d o n t he treat me nt 
gr o u p i nt o w hic h t he y are ra n d o mize d. 
•  
Per Pr ot oc ol ( P P) A nal ysis Set: A s u bset of s u bj ects i n t he mI T T A nal ysis Set 
w h o ha ve n o pr ot oc ol de viati o ns t hat affect t he G A lesi o n assess me nts 
( b y F A F). T his a nal ysis set will be use d f or se nsiti vit y a nal yses t o s u p p ort t he 
mI T T a nal yses.  
•  
Safet y A nal ysis Set: All treate d s u bjects . T his a nal ysis set will be use d f or all 
safet y a nal yses a n d s u bjects will be a nal yze d base d o n t he act ual treat me nt 
t he y recei ve.  
•  
P har mac o ki netic ( P K) A nal ysis Set: A s u bset of s u bjects i n t he Safet y 
A nal ysis Set w h o ha ve q ua ntifia ble P K meas ure me nts p ost first d ose. T his 
a nal ysis set will be use d f or all P K a nal yses a n d s u bjects will be a nal yze d 
base d o n t he act ual treat me nt t he y recei ve .  
 
Ge ner al St atistic al C o nsi der ati o ns  
I n ge neral, descri pti ve statistics i ncl u di n g t he n u m ber of n o n-missi n g o bser vati o ns 
( n), arit h metic mea n ( mea n), sta n dar d de viati o n ( S D), me dia n, mi ni m u m ( mi n), 
a n d ma xi m u m ( ma x) will be prese nte d b y treat me nt gr o u p f or c o nti n u o us 
varia bles. Fre q ue nc y a n d perce nta ge distri b uti o n will be prese nte d b y treat me nt 
gr o u p f or cate g orical varia bles.  
P ri m ar y Effic ac y A n al yses 
Pri m ary Esti m a n d  
T he esti ma n d f or t he pri mar y i nterest of t his st u d y is defi ne d as f oll o ws:  
1.  Treat me nt: N G M 6 2 1 Q 4 W, N G M 6 2 1 Q 8 W, a n d p o ole d S ha m ( S ha m 
i njecti o ns Q 4 W or Q 8 W). 
2.  P o p ulati o n: s u bjects wit h 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 as defi ne d b y t he i ncl usi o n- e xcl usi o n criteria of t he 
st u d y. 
3.  E n d p oi nt: rate of c ha n ge i n G A lesi o n area as meas ure d b y F A F o ver t he 
5 2 wee ks of treat me nt.  
4.  I nter-c urre nt e ve nts a n d t heir c orres p o n di n g strate gies: see  Secti o n  8. 3. 1. 1 . 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 2 6  of 9 6  
5.  P o p ulati o n -le vel s u m mar y: t he treat me nt gr o u p differe nce bet wee n eac h 
N G M 6 2 1 gr o u p a n d t he p o ole d S ha m gr o u p i n t he mea n c ha n ge fr o m 
baseli ne t o Wee k 5 2 i n t he G A lesi o n area as meas ure d b y F A F. 
M ai n Esti m ati o n  
T he G A lesi o n area (at baseli ne, Wee k 2 4 , a n d Wee k 5 2) will be a nal yze d us i n g a 
ra n d o m c oefficie nts m o del. T he m o del i ncl u des ter ms f or ti me (c o nti n u o us 
varia ble ass u mi n g li nearit y) a n d treat me nt -b y -ti me i nteracti o n. T he i nterce pt a n d 
sl o pe of ti me are ass u me d t o be ra n d o m effects wit h a bi variate n or mal distri b uti o n 
a n d a n u nstr uct ure d ( U N) c o varia nce matri x w hile t he treat me nt - b y-ti me 
i nteracti o n is ass u me d t o be a fi xe d effect. If t here is a c o n ver ge nce iss ue u n der t he 
ass u me d c o varia nce str uct ure ( U N) f or t he ra n d o m eff ect, t he n a varia nce-
c o m p o ne nts c o varia nce str uct ure will be use d. T he wit hi n -s u bject err ors are 
ass u me d t o be i n de pe n de nt a n d i de nticall y distri b ute d n or mal ra n d o m varia bles 
a n d are ass u me d t o be i n de pe n de nt of t he ra n d o m i nterce pt a n d ra n d o m sl o pe. 
Wit hi n t he fra me w or k of t his m o del, a p oi nt esti mate of t he treat me nt gr o u p 
differe nce i n t he re gressi o n sl o pe bet wee n eac h N G M 6 2 1 gr o u p a n d t he p o ole d 
S ha m gr o u p will be pr o vi de d. T he c orres p o n di n g t w o -si de d 9 5 % c o nfi de nce 
i nter val a n d p-val ue f or t he p oi nt es ti mate will als o be prese nte d.  
A hierarc hical testi n g pr oce d ure will be use d t o c o ntr ol t he fa mil y- wise t y pe -I 
err or rate ass ociate d wit h t he tests of t he t w o N G M 6 2 1 gr o u ps ( N G M 6 2 1 Q 4 W vs 
p o ole d S ha m a n d N G M 6 2 1 Q 8 W vs p o ole d S ha m). S pecificall y, t he c o m pa ris o n 
bet wee n N G M 6 2 1 Q 4 W a n d p o ole d S ha m will be perf or me d first. If t his test is 
statisticall y si g nifica nt at t he 5 % le vel, t he n t he c o m paris o n bet wee n N G M 6 2 1 
Q 8 W a n d p o ole d S ha m will be perf or me d. If t he first test is n ot statisticall y 
si g nifica nt at t he 5 % le vel, t he n t he c o m paris o n bet wee n N G M 6 2 1 Q 8 W a n d 
p o ole d S ha m will be c o nsi dere d e x pl orat or y. 
Se nsitivity A n alyses  
Se nsiti vit y a nal yses will be perf or me d t o assess t he r o b ust ness of t he mai n 
esti mat or of t he pri mar y esti ma n d. T hese se nsiti vit y a nal yses will be perf or me d 
wit h missi n g data i m p ute d b y t he m ulti ple i m p utati o n a p pr oac h usi n g t he Mar k o v 
C hai n M o nte Carl o ( M C M C) met h o d, a place b o- base d patter n mi xt ure m o del, a n d 
a ti p pi n g p oi nt met h o d, res pecti vel y. T he details of t hese a nal yses will be pr o vi de d 
i n t he statistical a nal ysis pla n (S A P ).  
I n a d diti o n, a se nsiti vit y a nal ysis will be perf or me d usi n g a n o nli near mi xe d 
effects m o del. I n t his m o del, t he i nterce pt is ass u me d t o be a n or mal ra n d o m 
varia ble, a n d t he mea n G A lesi o n area is ass u me d t o be a n e x p o ne ntial f u ncti o n of 
ti me wit h a se parate sl o pe ( of ti me) f or eac h treat me nt gr o u p. T he wit hi n-s u bject 
err ors are ass u me d t o be i n de pe n de nt a n d i de nticall y distri b ute d n or mal ra n d o m 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 2 7  of 9 6  
varia bles a n d are ass u me d t o be i n de pe n de nt of t he ra n d o m i nterce pt. T he details 
of t his a nal ysis will be pr o vi de d i n t he S A P. 
Sec o n d ar y Effic ac y A n al yses  
Sec o n dar y efficac y e n d p oi nts i ncl u de c ha n ge fr o m baseli ne at Wee k 5 2 i n G A 
lesi o n area, t he s q uare r o ot of G A lesi o n area, B C V A sc ore, L L V A letter sc ore, 
L L D i n E D T R S letters at a starti n g dista nce of 4 meters, bi n oc ular rea di n g s pee d 
( b y M N Rea d or Ra d ner rea di n g c harts), bi n oc ular critical pri nt size ( b y M N Rea d 
or Ra d ner rea di n g c harts), F RI c o m p osite sc ore, a n d N EI V F Q - 2 5, as well as 
c ha n ge a n d perce nt c ha n ge of C H 5 0 fr o m baseli ne. T he c ha n ge fr o m baseli ne will 
be a nal yze d usi n g a li near mi xe d- effects m o del. T he m o del i ncl u des fi xe d effects 
f or treat me nt, visit, treat me nt-b y -visit i nteracti o n, a n d t he baseli ne o utc o me val ue 
as a c o variate. T he c o varia nce str uct ure f or t his m o del will be ass u me d t o be 
u nstr uct ure d. If t he m o del d oes n ot c o n ver ge u n der t his ass u m pti o n, t he n a 
c o m p o u n d s y m metr y c o varia nce str uct ure will be use d. Wit hi n t he fra me w or k of 
t his m o del, a p oi nt esti mate of t he treat me nt gr o u p differe nce at Wee k 5 2 bet wee n 
eac h N G M 6 2 1 gr o u p a n d t he p o ole d S ha m gr o u p will be pr o vi de d. T he 
c orres p o n di n g t w o-si de d 9 5 % c o nfi de nce i nter val a n d p-val ue f or t he p oi nt 
esti mate will als o be prese nte d. 
S af et y A n al yses  
A d verse e ve n ts will be c o de d usi n g t he Me dical Dicti o nar y f or Dr u g Re g ulat or y 
Acti vities ( Me d D R A). Oc ular a n d s yste mic treat me nt -e mer ge nt a d verse e ve nts 
( T E A Es) will be s u m marize d b y pri mar y s yste m or ga n class a n d preferre d ter m. 
Act ual val ues a n d c ha n ge fr o m baseli ne  val ues f or vital si g ns, cli nical la b orat or y 
( he mat ol o g y a n d c he mistr y) tests a n d ot her c o nti n u o us varia bles ( b ot h oc ular a n d 
n o n- oc ular) will be s u m marize d wit h descri pti ve statistics. C o nc o mita nt 
me dicati o ns, p h ysical e xa mi nati o ns, a n d ot her cate g orical (safet y) varia bles ( b ot h 
oc ular a n d n o n- oc ular) will be s u m marize d wit h fre q ue nc y a n d perce nta ge 
distri b uti o n. All safet y a nal yses will be perf or me d usi n g t he Safet y A nal ysis Set.  
P h ar m ac o ki netics A n al yses  
I n di vi d ual a n d mea n ser u m N G M 6 2 1 c o nce ntrati o n –ti me data will be ta b ulate d 
a n d pl otte d b y c o h ort/ d ose le vel.   
 
 
A d diti o nal P K a nal yses a n d/ or s u m mar y statistics will be c o n d ucte d as 
a p pr o priate.  
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 2 8  of 9 6  
2  I ntr o d ucti o n 
2. 1  
B ac k gr o u n d  
2. 1. 1  
Ge o g r a p hic Atr o p h y ( G A)  
A ge -r elate d mac ular de ge nerati o n ( A M D) is a lea di n g ca use of bli n d ness i n t he U nite d States 
a n d t he de vel o p e d w orl d. It is esti mate d t hat ~ 1 9 6 milli o n ( M) pe o ple ha ve A M D gl o b all y 
a n d e x pecte d t o i ncrease t o 2 8 8 M b y 2 0 4 0 ( W o n g 2 0 1 4 ). A p pr o xi matel y 1 5. 7 M ha ve late 
sta ge dis ease, a n d t his n u m ber is e x pecte d t o i ncrease t o 2 6 M b y 2 0 4 0 (W o n g 2 0 1 4 ). 
T here  are t w o a d va nce d f or ms of A M D: t he ne o vasc ular/e x u dati ve f or m, als o referre d t o as 
wet A M D, a n d t he atr o p hic f or m, calle d ge o gra p hic atr o p h y ( G A). W hile ne o vasc ular A M D 
te n ds t o ca use m ore ra pi d a n d se vere visi o n l oss, it ca n be ma n a ge d wit h o n e of se veral 
a p pr o ve d i ntra vitr eal (I V T) a nti-V E G F t hera pies. G A ca us es m ore gra d ual, b ut rele ntlessl y 
pr o gressi ve a n d irre v ersi ble visi o n l oss. It was pre vi o usl y esti mate d t hat G A acc o u nt e d f or 
o ne-te nt h of t he bli n d ness d ue t o A M D, w hile ne o vasc ular A M D acc o u nte d f or t he re m ai n der 
(Ferris  1 9 8 4). D u e t o t he a d ve nt of a nti- V E G F t hera p y, rece nt st u dies ha v e re p orte d t hat G A 
acc o u nts f or a p pr o xi matel y o ne- q u arter of le gal bli n d ness i n t he U nite d Ki n g d o m a n d t he 
U nite d States ( H olz  2 0 1 4, B o yer  2 0 1 7). A n effecti ve t hera p y f or G A is o ne of t he m ost 
i m p orta nt u n met nee ds i n all of o p ht hal m ol o g y.  
2. 1. 2  
Mec h a nis m of Acti o n of N G M 6 2 1 
N G M 6 2 1 is a h u ma nize d I g G 1 a nti b o d y t hat p ote ntl y ( 0. 3 4 n M K D) i n hi bits h u ma n 
c o m ple me nt c o m p o ne nt 3 ( C 3), a n d t h us f u ncti o n all y i n hi bits classical a n d alter nati ve 
c o m ple me nt pr otei ns. S pecificall y, N G M 6 2 1 i n hi bits t he e nz y m atic clea va ge of C 3 b y 
C 3  c o n vertase. T h e  C 3a a n d C 3 b releas e pr o d ucts lea d t o d o w nstrea m acti vati o n of t he 
c o m ple me nt casca de t o me diate i m m u ne cell res p o nse as well as o ps o nizati o n acti vit y 
(va n  L o o ker e n Ca m pa g n e 2 0 0 7). M ore o v er, C 3 b ma y als o lea d t o f urt her acti vati o n of t he 
C 3  c o n vertase t o pr o p a gate t he c o m ple me nt acti vati o n res p o nse (Sa h u 2 0 0 1 ). N G M 6 2 1 is 
o nl y cr oss-reacti ve t o c y n o m ol g us m o n ke y C 3 wit h c o m para ble bi n di n g affi nit y a n d i n vitr o 
acti vit y t o t hat of h u ma n C 3. N G M 6 2 1 has bee n e n gi neere d wit h p oi nt m utati o ns i n t he 
Fc  r e gi o n t hat re d u ce bi n di n g t o Fcγ rece pt ors. 
N G M 6 2 1 is bei n g d e vel o pe d f or ge o gra p hic atr o p h y ( G A) sec o n dar y t o a ge- rel ate d mac ular 
de ge ner ati o n ( A M D). T h e pre d o mi na nt ge n etic ris k fact ors i n A M D, i ncl u di n g G A, i m plicate 
a d ysre g ulati o n of t he c o m ple me nt pat h wa y t hat is criticall y i m p orta nt i n 
i m m u ne/i nfla m mat or y r es p o nses (Ka n das a m y 2 0 1 7 , Da nis 2 0 1 5 ). Ge n o me-wi de ass ociati o n 
st u dies ha ve i de ntifie d p ol y m or p his ms i n a n u m ber of c o m ple m e nt pr otei ns ( C F H, C 2, C F B, 
C 3, C 7, C FI) ass ociate d wit h A M D, a n d precli nical data s u g gest t hat ge n etic varia nts i n 
c o m ple me nt fact ors lea ds t o a n o verall l o w -gra de acti vati o n of t he c o m ple me nt s yste m i n t he 
e ye t hat ma y lea d t o t he pat h o p h ysi ol o g y of A M D. Gi ve n t he p ote ntial r ole of c o m ple me nt 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 2 9  of 9 6  
acti vati o n i n t he pat h o ge nesis of G A, N G M 6 2 1 treat me nt i n t he e ye ma y re d uce t he 
i nfla m mati o n a n d tiss ue da ma ge ass o ciate d wit h c o m ple me nt acti vati o n, a n d, t h us, re d uce t he 
rate of r eti nal tiss ue da m a ge/atr o p h y. 
2. 1. 3  
T her a pe utic R ati o n ale f or N G M 6 2 1 i n Ge o g r a p hic Atr o p h y  
D ysr e g ulati o n of t he c o m ple me nt s yste m is a c o ntri b uti n g fact or t o t he pat h o p h ysi ol o g y of 
t he disease (K a n das a m y 2 0 1 7 ) d ue to se veral ge n etic p ol y m or p his ms ass o ciate d wit h G A 
sec o n dar y t o A M D. M ulti ple cli nical i n vesti gati o ns are e x pl ori n g t he effect of i n hi biti o n of 
vari o us c o m p o ne nts of t h e c o m ple me nt s yste m o n G A. T hese i ncl u d e i n hi biti n g Fact or D of 
t he alter nati ve p at h wa y wit h la m paliz u ma b, w hic h faile d i n late -sta ge cli nical de vel o p me nt; 
i n hi biti n g t he C 5 c o m p o ne nt of t he late c o m ple m e nt s yste m, w hic h h as pr o d uce d c o nflicti n g 
res ults; a n d i n hi biti n g t he C 3 c o m p o ne nt of t he c o m ple me nt s yste m. C 5 cli nical trials ha ve 
i ncl u de d i ntra ve n o us (I V) ec uliz u ma b ( Ale xi o n P har mace uticals), w hic h di d n ot decreas e t he 
gr o wt h rate of G A ( N C T 0 0 9 3 5 8 8 3 ); L F G 3 1 6 ( N o vartis), w hic h w as ter mi nate d f or f utilit y 
(Ye h os h ua 2 0 1 4 , N C T 0 1 5 2 7 5 0 0 ); a n d Zi m ura ™ (a vaci nca pta d pe g ol; I v eri c Bi o (f or merl y 
O p ht h otec h)), w hi c h di d re d uce G A gr o wt h i n a rece ntl y c o m plete d P hase 3 st u d y 
(N C T 0 2 6 8 6 6 5 8 ). Pe gcet ac o pla n ( pre vi o usl y AP L - 2; A pellis P har mace uticals), a C 3 -tar gete d 
i n hi bit or, als o re p orte d a si g nifica nt re d ucti o n i n t he gr o wt h of G A l esi o n size i n a P hase 2 
st u d y of (N C T 0 2 5 0 3 3 3 2 ). H o we ver, b ot h a vaci nca pta d pe g ol a n d A P L-2 are pe g ylate d  a n d 
are ass o ciate d wit h a n i n creas e i n t he i nci de nce of C N V i n s u bjects ( Si n g h  2 0 1 8, I V E RI C 
press release 2 0 1 9 ), c o nfir mi n g o bser vati o ns fr o m r o de nt m o dels of C N V t h at s u g gest t hat 
pe g yl ati o n ma y l ea d t o i ncreas e d vasc ul ar lea ka ge ( Par k 2 0 1 9 ). 
N G M 6 2 1, a C 3 clea v a ge i n hi bit or, ma y offer a n efficac y as well as safet y a d va nta ge o ver 
t hese lea di n g ca n di dates i n cli nical de vel o p me nt, gi ve n its p ote nc y i n i n hi biti n g clea v a ge of 
C 3 a n d its a bse nce of p e g ylati o n. 
2. 1. 4  
Ge o g r a p hic Atr o p h y a n d C urre nt Tre at me nts  
T here is n o c urre ntl y a p pr o ve d treat me nt f or G A. 
2. 2  
S u m m ar y of N o ncli nic al St u dies  
T he p har mac ol o g y, p har mac o ki netics, a n d safet y pr ofile of N G M 6 2 1 are d etaile d i n t he 
c urre nt v ersi o n of t he N G M 6 2 1 I n v esti gat or’s Br oc h ure (I B).  
I n vitr o f u ncti o nal acti vit y ass a ys ha ve d e m o nstrat e d t he a bilit y of N G M 6 2 1 t o i n hi bit b ot h 
t he clea v a ge of C 3 t o C 3a a n d t he c o m ple m e nt-me diate d he m ol y sis i n c y n o m ol g us m o n ke y 
a n d h u ma n ser a. I n c y n o m ol g us m o n ke ys, N G M 6 2 1 de m o nstrate d p har m ac ol o gical acti vit y 
f oll o wi n g I V or I V T a d mi nistrati o n at hi g h d oses d ue t o its a bilit y t o i n hi bit 
c o m ple me nt -me diate d h e m ol ysis.  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 0  of 9 6  
T he p har mac o ki netic ( P K) pr ofile of N G M 6 2 1 w as e val uate d i n t he ra b bit a n d t he 
c y n o m ol g us m o n ke y f oll o wi n g I V T a n d/ or I V a d mi nistrati o n. N G M 6 2 1 e x p os ure i n oc ular 
tiss ues i ncrease d i n a d os e- de pe n d e nt ma n ner; t1/ 2 of N G M 6 2 1 ra n ge d fr o m a p pr o xi matel y 
3. 0 t o 3. 5 da ys i n oc ular tiss ue. N G M 6 2 1 w as als o meas ura ble i n ser u m f oll o wi n g I V T 
i njecti o n wit h a P K pr ofile c o nsiste nt f or a m o n o cl o nal a nti b o d y. I n t h e c y n o m ol g us m o n ke y, 
t he s yste mic t1/ 2 of N G M 6 2 1 was a p pr o xi matel y 1 0 da ys f oll o wi n g I V or I V T i njecti o n. 
T here w as n o mea ni n gf ul acc u m ulati o n of N G M 6 2 1 after re peat o nce m o nt hl y I V T d osi n g i n 
t he c y n o m ol g us m o n ke y. O verall, t he p har mac o ki netic ( P K) pr o p erties o bs er ve d f or 
N G M 6 2 1 i n t he c y n o m ol g us m o n ke y w ere c o nsiste nt wit h t h ose e x pecte d f or a h u ma nize d 
I g G 1 a nti b o d y. T he oc ul ar p har m ac o ki netic a n d p har mac o d y n a mic ( P K P D) pr ofile of 
N G M 6 2 1 i n c y n o m ol g us m o n ke ys f oll o wi n g I V T i njecti o n s u p p orts e ver y 4- a n d 8- w ee k 
d osi n g re gi me ns. 
T he n o ncli nical saf et y of N G M 6 2 1 was ass esse d i n t he c y n o m ol g us m o n ke y f or u p t o 
2 8 wee ks of re peat d osi n g wit h a 1 2- w ee k treat me nt -free p eri o d. T he c y n o m ol g us m o n ke y 
was t he o nl y rele v a nt s pecies i n w hic h t o assess t h e n o ncli nical safet y of N G M 6 2 1 base d o n 
p har mac ol o gic acti vit y of t he m olec ule.  
N G M 6 2 1 was w ell t olerate d i n c y n o m ol g us m o n k e ys u p t o t he hi g hest d os e test e d 
( 1 2. 1 m g/e ye) w h e n a d mi nistere d o nce e ver y 4 w ee ks b y I V T i njecti o n f or 2 8 wee ks 
(se ve n d oses t otal) (St u d y N G M 6 2 1 -T X - 0 4). N G M 6 2 1 pr o d uce d n o effect o n cli nical 
pat h ol o g y a n d uri ne c h e mistr y par a meters u p t o 2 8 wee ks of treat me nt. N G M 6 2 1 ha d n o 
effect o n saf et y p h ar mac ol o g y par a meters ( b o d y t e m perat ure, car di o vasc ul ar e n d p oi nts, 
res pirati o n rat e, a n d bl o o d gas p ara m eters) w he n e val uate d i n t he 5- w ee k m o n ke y t o xic ol o g y 
st u d y. T here w ere n o o c ular cli nical si g nals t hat w ere c o nsi d ere d relate d t o N G M 6 2 1 
a d mi nistrati o n, wit h t he e x ce pti o n of bilateral oc ular i nfla m mati o n n ote d i n o ne a ni mal d ose d 
at 1 2. 1 m g/e ye. T his c ha n ge was c o nsi dere d sec o n dar y t o t he de vel o p me nt of a n 
A D A - me diate d i m m u n o ge ni cit y r es p o nse a n d n ot rele va nt t o h u ma n safet y. N o mea ni n gf ul 
c ha n ges i n i ntra o c ular pr ess ure w ere attri b ute d t o N G M 6 2 1 treat me nt.  
At 2 8 wee ks, t her e were n o N G M 6 2 1-rel ate d effects o n or ga n wei g ht or o n macr osc o pic or 
micr osc o pic e v al uati o n of s yste mic tiss ues or t he e ye  f oll o wi n g I V T i njecti o n. N o e vi de nce 
f or s yst e mic C 3 i n hi biti o n was n ote d f oll o wi n g I V T i njecti o n u p t o t he hi g h est d ose teste d. 
N G M 6 2 1 was als o w ell t olerate d f oll o wi n g I V ( 9 m g/ k g) a d mi nistrati o n, w here hi g her 
s yste mic e x p os ure w as ac hie ve d, a n d n o s yste mic effects were n ote d.  
Base d o n t h e c u m ulati ve n o ncli nical safet y pr ofile of N G M 6 2 1 f or u p t o 2 8 wee ks of 
treat me nt i n t he c y n o m ol g us m o n ke y, t he n o- o bser ve d-a d v erse -effect le v el (N O A E L ) was 
deter mi ne d t o be 1 2. 1 m g/e ye, t he ma xi mal feasi ble I V T d ose. T h e e x p os ure mar gi ns i n t he 
e ye at t he N O A E L w ere ~ 1. 6 -f ol d a b o ve t he pr o p ose d d ose of 1 5 m g/e ye. T he e x p os ure 
mar gi ns f or s yste mic e x p os ure (ser u m A U C 0 – 2 8 d) of a p pr o xi matel y 2 7-f ol d e xist bet wee n t he 
N O A E L i n a ni mal t o xicit y st u dies relati ve t o t he 1 5 m g/e ye d os e.  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 1  of 9 6  
2. 3  
S u m m ar y of Cli nic al St u dies  
N G M c o n d ucte d a P hase 1 ( St u d y 1 8- 0 5 0 1 ) first-i n- h u ma n m ultice nter, o p e n la bel, 
si n gle- d os e a n d m ulti ple- d ose escal ati o n st u d y of t he safet y, t olera bilit y, a n d 
p har mac o ki ne tics of I V T i njecti o ns of N G M 6 2 1 i n s u bjects wit h ge o gra p h y atr o p h y 
sec o n dar y t o a ge-relate d mac ular de ge nerati o n.  
A t otal of 9 s u bjects ( 3 s u bjects per d ose) were  d ose d wit h eit her 2, 7. 5, or 1 5 m g N G M 6 2 1 
b y I V T i njecti o n i n t he si n gle asce n di n g d ose ( S A D) p orti o n of t he st u d y, a n d 6 s u bjects 
were  d os e d t wice (se parate d b y 4 w ee ks) wit h 1 5 m g N G M 6 2 1 i n t he m ulti-d ose ( M D) 
p orti o n of t he st u d y. All 1 5 s u bjects c o m plete d t h e 1 2- wee k f oll o w- u p. 
N G M 6 2 1 was w ell t olerate d w he n a d mi nistere d as a si n gle I V T d ose of 2, 7. 5, or 1 5 m g a n d 
as m ulti ple I V T d os es of 1 5 m g ( t w o d oses 4 wee ks a part). T h e n u m ber of s u bjects re p orti n g 
T E A Es was si milar f or eac h d ose le v el i n t he S A D c o h orts a n d f or t he M D c o h ort. 
O verall , 9 s u bjects ( 6 0. 0 %) ha d 1 4 T E A Es i ncl u di n g 4 s u bjects ( 2 6. 7 %) t h at ha d oc ular 
T E A Es. N o  d ose-relate d tre n d i n t he n u m ber of s u bjects re p orti n g treat me nt e mer ge nt 
a d verse e ve nts ( T E A Es)  was o bser v e d . N o T E A Es were S A Es or c o nsi dere d b y t h e 
I n v esti gat or t o be r elate d t o N G M 6 2 1 a d mi nistrati o n, a n d t he maj orit y of T E A Es were mil d 
i n se verit y. N o T E A Es w ere seri o us or lea d t o st u d y wit h dra wal (T a ble  1). 
 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 2  of 9 6  
T a ble 1. 
St u d y 1 8 0 5 0 1 : Fre q ue n c y of Tre at me nt E mer g e nt A d verse E ve nts 
( All C a us alities)  
M e d D R A S O C  
Preferre d ter m  
Tre at me nt  
O ver all  
( N = 1 5) 
S A D C o h orts  
M D C o h ort  
1 5 m g N G M 6 2 1  
( N = 6) 
2 m g N G M 6 2 1  
( N = 3) 
7. 5 m g N G M 6 2 1  
( N = 3) 
1 5 m g N G M 6 2 1  
( N = 3) 
Car diac dis or ders  
0 
0 
1 ( 3 3. 3) [ 1]  
0 
1 ( 6. 7) [ 1]  
Ve ntric ular e xtras yst oles  
0  
0  
1 ( 3 3. 3) [ 1]  
0  
1 ( 6. 7) [ 1]  
E ye dis or ders  
0 
1 ( 3 3. 3) [ 1]  
0 
3 ( 5 0. 0) [ 4]  
4 ( 2 6. 7) [ 5]  
C o nj u ncti val hae m orr ha ge  
0  
0  
0  
2 ( 3 3. 3) [ 3]  
2 ( 1 3. 3) [ 3]  
E ye pr urit us  
0 
1 ( 3 3. 3) [ 1]  
0 
1 ( 1 6. 7) [ 1]  
2 ( 1 3. 3) [ 2]  
Gastr oi ntesti nal dis or ders  
0  
1 ( 3 3. 3) [ 1]  
0  
0  
1 ( 6. 7) [ 1]  
Diarr h oea  
0 
1 ( 3 3. 3) [ 1]  
0 
0 
1 ( 6. 7) [ 1]  
I nfecti o ns a n d i nfestati o ns 
1 ( 3 3. 3) [ 1]  
1 ( 3 3. 3) [ 1]  
0  
0  
2 ( 1 3. 3)  [ 2] 
Di vertic ulitis  
0 
1 ( 3 3. 3) [ 1]  
0 
0 
1 ( 6. 7) [ 1]  
P ne u m o nia  
1 ( 3 3. 3) [ 1]  
0  
0  
0  
1 ( 6. 7) [ 1]  
Ne o plas ms be ni g n, 
mali g na nt , a n d u ns pecifie d 
(i ncl c ysts a n d p ol y ps) 
1 ( 3 3. 3) [ 1]  
0 
0 
0 
1 ( 6. 7) [ 1]  
B asal cell carci n o ma  
1 ( 3 3. 3) [ 1]  
0  
0  
0  
1 ( 6. 7) [ 1]  
Ner v o us  s yste m dis or ders 
0 
0 
1 ( 3 3. 3) [ 1]  
1 ( 1 6. 7) [ 2]  
2 ( 1 3. 3) [ 3]  
Hea dac he  
0  
0  
0  
1 ( 1 6. 7) [ 1]  
1 ( 6. 7) [ 1]  
H y p oaest hesia  
0 
0 
0 
1 ( 1 6. 7) [ 1]  
1 ( 6. 7) [ 1]  
Sciatica  
0  
0  
1 ( 3 3. 3) [ 1]  
0  
1 ( 6. 7) [ 1]  
Re pr o d ucti ve s yste m a n d 
breast dis or ders  
1 ( 3 3. 3) [ 1]  
0 
0 
0 
1 ( 6. 7) [ 1] 
B e ni g n pr ostatic h y per plasia  
1 ( 3 3. 3) [ 1]  
0 
0 
0 
1 ( 6. 7) [ 1]  
( ) = perce nta ge of s u bj ects wit h a d verse e ve nts; [ ] = n u m ber of a d verse e ve nts. . 
 
O verall , oc ular saf et y was fa v ora ble. Mil d oc ul ar T E A Es of c o nj u ncti val h e m orr ha ge a n d e ye 
pr urit us were eac h e x perie nce d b y 2 s u bjects. C o nj u ncti val he m orr ha ges w ere li kel y d ue t o 
t he i njecti o n pr oce d ure a n d res ol ve d o n t heir o w n a n d t he 2 cas es of e ye pr urit us were 
res ol ve d wit h artifici al tears. N o s u bjects e x perie n ce d e n d o p ht hal mitis, oc ular i nfla m mati o n, 
or C N V i n eit her e ye o ver t he 1 2- wee k f oll o w- u p peri o d.  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 3  of 9 6  
N o visi o n- relate d safet y si g nals were d etecte d. N o cli nicall y si g nifica nt slit -la m p 
bi o micr osc o p y fi n di n gs were re p orte d fr o m bas eli ne t o t he e n d of st u d y f oll o wi n g 
e x a mi nati o n of e ye li ds/las hes, c or n ea, iris, le ns, a n d o ptic ner ve f or b ot h e yes f or all 
s u bjects. As e x pecte d i n G A s u bjects, t here were cli nicall y si g nifica nt fi n di n gs f or t h e 
mac ula e x a mi nati o n re p orte d at scree ni n g/ baseli ne b ut t here was n o cli nicall y si g nifica nt 
o p ht hal m osc o p y fi n di n gs p ost- baseli ne t hr o u g h t h e e n d of t he st u d y f oll o wi n g t he vitre o us, 
peri p her al reti na, a n d c h or oi d e x a mi nati o n of b ot h e yes. 
At d ose le vels w here t he d ose v ol u me was 1 0 0 µ L ( 2 a n d 1 5 m g N G M 6 2 1) t he maj orit y of 
s u bjects ha d tra nsie nt i ncreases i n I O P at 1 5 mi n utes p ost‑i njecti o n. T hree p atie nts ha d I O P 
rec or di n gs of 2 5 or 2 6 m m H g at t he 1 5 - mi n ute p ost-i njecti o n I O P b ut t he press ure ret ur ne d 
t o t he n or mal ra n ge b y 6 0 mi n utes p ost-i njecti o n. O verall, mi ni mal i m pact t o pre-d ose I O P 
was o bser v e d fr o m bas eli ne t o 1 2 wee ks. 
E val uati n g efficac y w as u nfeasi ble d ue t o t he s h ort ti me wi n d o w, s mall sa m ple size, a n d 
a bse nce of c o ntr ol. T h e st u d y e ye G A lesi o ns, as asse sse d b y F A F, w ere ge nerall y sta ble o ver 
t he 1 2-wee k f oll o w‑ u p p eri o d f or i n di vi d ual s u bjects o n eac h treat me nt. Ce nter p oi nt 
t hic k ness a n d t otal reti nal v ol u me were si milar o v er t he 1 2- w ee k f oll o w- u p peri o d i n t he 
st u d y e ye. T he B C V A assess me nt ( E T D R S B C V A) was use d f or safet y p ur p oses. 
O n  a ver a ge s u bjects mai ntai ne d or i m pr o ve d t heir vis ual ac uit y o v er t he 1 2-wee k f oll o w - u p. 
N o safet y c o n cer ns wer e n ote d d uri n g t he st u d y b ase d o n cli nical la b orat or y e val uati o ns, vital 
si g ns, 1 2-lea d E C Gs, a n d p h ysical e x a mi nati o ns. No safet y patter ns or c o n cer ns w ere 
i de ntifie d t hat w o ul d precl u de f urt her i n vesti gati o n of N G M 6 2 1. 
Ser u m P K sa m ples were o btai ne d at pre d eter mi ne d ti me p oi nts o ut t o  8 4 da ys  p ost- d ose. 
T he  ser u m P K of N G M 6 2 1 f oll o wi n g I V T i njecti o n was li near a n d d ose- pr o p orti o nal wit h 
l o w acc u m ulati o n rati o f oll o wi n g e ver y 4 wee k re peat d osi n g. F oll o wi n g a si n gle a n d re peat 
I V T a d mi nistrati o n, N G M 6 2 1 e x hi bite d sl o w s yste mic a bs or pti o n wit h t he me dia n Tma x  of 
bet wee n 7. 0 5 a n d 1 3. 9 5 da ys. T h e mea n C L/ F was bet wee n 2 3 2. 0 5 a n d 2 7 5. 5 9 m L/ da y a n d 
t he mea n ter mi nal half-life was b et wee n 1 2. 2 7 a n d 1 4. 8 9 da ys. T h ere was a 
d ose- pr o p orti o nal i ncr eas e i n N G M 6 2 1 acr oss t he 2 t o 1 5 m g d ose ra n ge, b ase d o n C ma x  a n d 
A U C 0 – i nf. F oll o wi n g t he r e peat I V T d ose of 1 5 m g e ver y 4 w ee ks, the acc u m ulati o n rati o was 
1. 5 0 a n d 1. 6 1 base d o n C ma x  a n d A U C, res pecti vel y. 
F oll o wi n g I V T a d mi nistr ati o n of N G M 6 2 1 ser u m e x p os ure was bel o w c o n ce ntrati o ns t hat 
pr o d uce s yste mic c o m ple me nt i n hi biti o n. A d diti o nall y, all s u bjects w ere a nti dr u g a nti b o d y 
( A D A) n e gati ve at b aseli ne a n d all f oll o w - u p ti me p oi nts t hr o u g h t he 1 2- w ee k st u d y d ur ati o n. 
F or a d diti o nal details r e gar di n g n o ncli nical a n d cli nical st u dies, see t he N G M 6 2 1 
I n v esti gat or’s Br oc h ure. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 4  of 9 6  
2. 4  
R ati o n ale f or D ose a n d Re gi me n Selecti o n  
T he N G M 6 2 1 d ose a n d d ose re gi me n is base d o n t he safet y a n d t olera bilit y of N G M 6 2 1 i n 
P hase 1 St u d y 1 8- 0 5 0 1  as well as t he p har mac o ki netic a n d p har m ac o d y na mic ( P K P D) pr ofile 
of N G M 6 2 1. T he 1 5 m g m o nt hl y ( Q 4 W) d osa ge was t he ma xi m u m e val uate d d osi n g 
re gi me n i n P hase 1 St u d y 1 8- 0 5 0 1 . P K P D si m ulati o ns i nc or p orati n g b ot h C 3 tar get 
e n ga ge me nt a n d i n hi biti o n p ote nc y de m o nstrate d t hat b ot h Q 4 W a n d Q 8 W d osi n g 
fre q ue n cies will res ult i n a desira ble ra n ge of re d u cti o n i n C 3 a n d i n hi biti o n of its acti vit y 
f oll o wi n g a 1 5 m g I V T i njecti o n. Alt h o u g h t he e xte nt of C 3 tar get e n ga ge me nt re q uire d f or 
cli nical efficac y is u n k n o w n, it is a ntici pate d t hat t he d ose a n d d ose re gi me n selecte d  w o ul d 
be s ufficie nt f or acti vit y. T h us, t he N G M 6 2 1 d ose of 1 5 m g w as selecte d f or I V T 
a d mi nistrati o n at Q 4 W or Q 8 W i nter vals t o pr o vi de d ose ra n gi n g d ata a n d i nf or m o pti mal 
d osi n g fr e q ue n c y f or f ut ure st u dies. T he 1 5 m g a d mi nistere d Q 8 W is e x pecte d t o ac h ie ve 
l o wer s yste mic dr u g e x p os ures relati ve t o 1 5 m g Q 4 W w hile mai ntai ni n g effecti ve 
c o nce ntr ati o ns f or acti vit y i n oc ular tar get tiss ues. A d diti o nall y, t he Q 8 W d osi n g re gi me n 
re pres e nts less of a tr eat me nt b ur de n t o s u bjects, care gi v ers, a n d p h ysici a ns relati ve t o a 
Q 4 W d osi n g re gi me n. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 5  of 9 6  
3  St u d y O bjecti ves a n d E n d p oi nts  
3. 1  
Pri m ar y O bjecti ves a n d E n d p oi nts  
T he pri mar y o bjecti ves of t his st u d y are t o e val uat e t he efficac y a n d safet y of N G M 6 2 1 
i ntra vitreal (I V T) i njecti o ns a d mi nistere d e ver y 4 or 8 wee ks f or a t otal of 5 2 wee ks.  
•  T he pri mar y efficac y e n d p oi nt is t he rate of c ha n ge i n G A lesi o n area as m eas ure d b y 
f u n d us a ut ofl u ores ce nce ( F A F) o ver t he 5 2 w ee ks of treat me nt.  
•  T he pri mar y safet y e n d p oi nts will e val uate t he i nci de nce a n d se verit y of o c ular a n d 
s yste mic a d v erse e ve nts fr o m treat me nt wit h N G M 6 2 1 a d mi nistere d e ver y 4 or 8 wee ks 
c o m pare d t o S ha m. 
3. 2  
Sec o n d ar y O bjecti ves a n d E n d p oi nts  
T he sec o n d ar y o bjecti ves of t his st u d y are t o e val u ate t he 1) sec o n dar y effi cac y , 
2) p har mac o ki netics ( P K), a n d 3) i m m u n o ge nicit y of N G M 6 2 1 a d mi nistere d e ver y 4 or 
8 wee ks i n s u bjects wit h G A. 
T he f oll o wi n g e n d p oi nts will be meas ure d:  
1.  
Sec o n dar y Efficac y E n d p oi nts:  
A.  C ha n ge fr o m bas eli ne at Wee k 5 2 i n: 
a. G A lesi o n area as assesse d b y F A F ( m m 2/ yr) 
b.  T he s q uare r o ot of G A l esi o n area ( m m) 
c. B C V A sc or e as assesse d b y E T D R S c h art at a starti n g dista nce of 4 meters  
d.  L L V A sc or e as ass esse d b y E T D R S c h art at a starti n g dista nce of 4 meters  
e. L o w L u mi na n ce D eficit ( L L D; B C V A – L L V A) i n E T D R S letters at a starti n g 
dista nce of 4 meters  
f. Bi n oc ular rea di n g s p ee d b y M N Rea d or Ra d ner rea di n g c harts   
g.  Bi n oc ular critical pri nt si ze as assesse d b y M N Rea d or Ra d ner rea di n g c harts  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 6  of 9 6  
h.  F u ncti o nal Rea di n g I n d e pe n de nce I n de x ( F RI) c o m p osite sc ore  
i. N EI V F Q - 2 5 c o m p osite sc ore, near acti vit y s u bscale sc ore, dista nce acti vit y 
s u bscale sc or e  
B.  C ha n ge a n d perce nt c ha n ge of s yste mic c o m ple me nt acti vit y ( C H 5 0) fr o m baseli ne at 
eac h visit.  
2.  
Sec o n dar y P har m ac o ki netics E n d p oi nt:  
A.  Ser u m tr o u g h c o nce ntr ati o n of N G M 6 2 1 
3.  
Sec o n dar y I m m u n o ge ni cit y E n d p oi nt: 
A.  T he i nci de nce of a nti- N G M 6 2 1 a nti b o dies ( A D As) i n ser u m 
3. 3  
E x pl or at or y O bjecti ves a n d E n d p oi nts  
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 8  of 9 6  
4. 3  
D at a S af et y M o nit ori n g B o ar d 
A n i n de pe n de nt D ata a n d Safet y M o nit ori n g B oar d ( D M S B) m o nit ors safet y a n d st u d y 
c o n d uct o n a n o n g oi n g b asis. T he D S M B will be esta blis he d u n der a s e parate c harter, w hi c h 
will detail t he r oles/res p o nsi bilities a n d f u ncti o n of t he D S M B. Me m bers of t he D S M B are 
e xter nal t o t he S p o ns or a n d will c o nsist of at least 2 or m ore i n de pe n d e nt p h ysicia ns. 
T he  D S M B will meet a p pr o xi matel y e ver y 6 m o nt hs (a n d a d h oc as nee d e d). T he D S M B will 
be pr o vi de d data t h at ar e s u m marize d b y treat me nt ar m usi n g mas k e d treat me nt ar m la bels 
(i.e., A, B, C). After re vi e wi n g t h e data b y mas k e d treat me nt ar m, t he D S M B ma y re q uest t o 
re vie w u n mas k e d data if dee me d necessar y t o assess t he be nefit–ris k pr ofile of N G M 6 2 1.  
T he D S M B will ma ke r ec o m me n dati o ns t o t he S p o ns or re gar di n g f urt her c o n d uct of t he 
st u d y (i.e. c o nti n ue as desi g ne d, c o nti n ue wit h mi n or or maj or m o dificati o ns, or st u d y 
ter mi nati o n). N o f or mal efficac y or f utilit y a nal ysis is pla n ne d f or t he st u d y. T he S p o ns or 
will re mai n mas ke d t o all data tra nsfers pr o vi de d t o t he D S M B (see Secti o n  6. 3. 1  f or 
i nf or mati o n a b o ut u n mas ki n g f or S A Es). 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 3 9  of 9 6  
5  S u bject Selecti o n  
5. 1  
I ncl usi o n Criteri a  
S u bjects w h o meet t he f oll o wi n g criteria will be i ncl u de d i n t he st u d y:  
1.  Male or fe m ale ( n o n - pre g na nt, n o n-lactati n g) s u bjects ≥ 5 5 of a ge 
2.  Sta n dar d l u mi na nce B C V A sc ore of 3 4 letters or better usi n g E T D R S c harts at t he 
starti n g dista nce of 4 met ers (a p pr o xi matel y 2 0/ 2 0 0 S nelle n e q ui vale nt or b etter ) i n 
st u d y e ye 
3.  Cli nical dia g n osis of G A sec o n dar y t o A M D wit h t he G A lesi o n meeti n g t he 
f oll o wi n g criteria as d eter mi ne d b y t he ce ntral rea di n g ce nter's ass ess me nt of F u n d us 
A ut ofl u oresce nce ( F A F) i ma gi n g at scree ni n g:  
a)  T otal G A ar ea m ust be ≥ 2. 5 a n d ≤ 1 7. 5 m m 2  
b)  If G A is m ultif ocal, at least o ne f ocal lesi o n m ust be ≥ 1. 2 5 m m2 ( 0. 5 D A), wit h 
t he o verall area of G A ≥ 2. 5 a n d ≤ 1 7. 5 m m2 
c)  T he e ntire G A lesi o n m ust be c o m pletel y vis u alize d o n t he mac ula -ce nt ere d 
i ma ge a n d m ust be a ble t o be i ma ge d i n its e ntiret y a n d n ot c o nti g u o us wit h a n y 
areas of peri p a pillar y atr o p h y.  
d)   Prese nce of ba n de d or diff use patter n of h y per-a ut ofl u oresce n ce i n t he j u ncti o nal 
z o ne of G A. A bse nce of h y per-a ut ofl u oresce nce i n t he j u ncti o nal z o ne of t he G A 
(i.e., patter n = n o ne) is e x cl u de d. 
e)  Well de marcate d G A wit h n o a nat o mical e vi de n ce (as assesse d b y F A a n d 
S D -O C T) of c urre nt or pri or C N V i n t he st u d y e ye 
4.  Clear oc ular m e dia a n d a de q uate p u pil dilatati o n a n d fi x ati o n i n b ot h e yes t o per mit g o o d 
q ualit y p h ot o gra p hic i ma gi n g 
5.  Fe male s u bjects m ust be eit her of a) n o n-c hil d beari n g p ote ntial, defi n e d as w o me n w h o 
ha ve ha d a h ysterect o m y, bilateral o o p h orect o m y, me dicall y d o c u me nte d o varia n fail ure, 
d oc u me nte d p ost me n o pa usal, or a f ollicle sti m ulati n g h or m o ne > 4 0 mI U/ m L, or b) if of 
c hil d beari n g p ote ntial, defi ne d as w o me n wit h < 2 years of a me n orr h ea (a bs e nce of 
me nstr uati o n), t he n m ust ha ve a n e gati ve ser u m pre g n a nc y test at Scree ni n g a n d uri ne 
pre g na nc y t est at t he Da y 1 visit pri or t o first d ose of st u d y dr u g. 
6.  Fe male s u bjects of c hil d beari n g p ote ntial a n d mal e s u bjects wit h a fe m ale part ner of 
c hil d beari n g p ote ntial m ust eit her be a bsti ne nt or be usi n g c o nsiste nt a n d a de q uate birt h 
c o ntr ol fr o m Scree ni n g t o E n d of St u d y ( E O S / Wee k 5 6). O n e of t he f oll o wi n g f or ms of 
c o ntrace pti o n is re q uire d:  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 0  of 9 6  
a)   C o n d o m  
b)   H or m o ne-c o nt ai ni n g c o ntrace pti ve  
c)  I ntr a uteri ne d e vice wit h a fail ure rate < 1 % per year  
d)   Cer vical ca p or dia p hr a g m wit h s per mici dal a ge nt  
e)  T u bal sterilizati o n  
f)  Vasect o m y i n male part n er  
7.  Willi n g a n d a ble t o gi ve i nf or me d c o ns e nt, writte n l ocal pri vac y re q uire m e nts, c o m pl y 
wit h all visit pr oce d ures a n d li kel y t o c o m plete t h e st u d y 
5. 2  
E xcl usi o n Criteri a  
S u bjects will be e x cl u de d if t he y meet t he f oll o wi n g criteria:  
5. 2. 1  
Oc ul ar E xcl usi o ns  
5. 2. 1. 1  
St u d y E ye  
1.  Hist or y of pri or I V T i njecti o n f or ne o vasc ular A M D (see e xce pti o n bel o w), vitrect o m y 
s ur ger y, s u b mac ul ar s ur ger y, or a n y s ur gical i nter ve nti o n f or A M D. A si n gle I V T 
i njecti o n of a nti-V E G F, if a d mi nistere d > 2 years pri or t o scree ni n g, is per mitte d.  
A si n gle i ntra o p erati ve a d mi nistrati o n of a c ortic oster oi d d uri n g cataract s ur ger y f or 
c yst oi d mac ul ar e d e ma pr o p h yla xis at least 3 m o nt hs pri or t o scree ni n g is p er mitte d.  
2.  G A sec o n d ar y t o a c o n diti o n ot her t ha n A M D i n eit her e ye (e. g., m o n o ge n etic mac ular 
d ystr o p hies li ke Star gar dt disease, c o ne r o d d ystr o p h y, or t o xic mac ul o pat hies). 
3.  A n y hist or y of or acti ve c h or oi dal ne o vas c ularizati o n ( C N V), base d o n fl u orescei n 
a n gi o gr a p h y ( F A) a n d S D- O C T i ma gi n g as assesse d b y t h e Ce ntral Rea di n g Ce nter.  
4.  Pre vi o us laser p h ot oc oa g ulati o n f or C N V, dia betic mac ular e d e ma ( D M E), reti nal vei n 
occl usi o n a n d pr oliferati ve dia betic reti n o pat h y. 
5.  I ntr a oc ular s ur ger y (i ncl u di n g le ns re place me nt s ur ger y) wit hi n 3 m o nt hs pri or t o 
ra n d o mizati o n. 
6.  Hist or y of l aser t hera p y i n t he mac ular re gi o n. 
7.  A p ha kia or a bs e nce of t h e p osteri or ca ps ule. N ote: yttri u m al u mi n u m gar net ( Y A G) las er 
p osteri or ca ps ul ot o m y f or p osteri or ca ps ule o pacificati o n d o ne at least 6 0 d a ys pri or t o 
scree ni n g is n ot e x cl u de d. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 1  of 9 6  
8.  A n y o c ular c o n diti o n ot her t ha n G A s ec o n dar y t o A M D t hat ma y re q uire s ur ger y or 
me dical i nter ve nti o n (i ncl u di n g le ns re pl ace m e nt s ur ger y) d uri n g t h e st u d y peri o d or, i n 
t he o pi ni o n of t he I n vesti gat or, c o ul d c o m pr o mise vis ual f u ncti o n d uri n g t h e st u d y 
peri o d. 
9.  A n y c o ntrai n dicati o n t o I V T i njecti o n i ncl u di n g c urre nt oc ular or peri oc ular i nfecti o n. 
1 0.  A ut oi m m u ne u veitis or scleritis, or c hr o nic i nfl a m mat or y disease of a nteri or se g me nt, 
i ncl u di n g c hr o ni c ker at oc o nj u ncti vitis sicca ( m ore t ha n mil d) or i nfla m mat or y ble p h aritis 
( n o ni nfecti o us) of eit her e ye ( greater t ha n mil d se verit y), or c hr o nic i nfla m mat or y disease 
of p osteri or c h a m ber. 
5. 2. 1. 2  
Fell o w ( N o n-st u d y) E ye 
1 1.  A n y hist or y of or acti ve c h or oi dal ne o vas c ularizati o n ( C N V) less t ha n 2 years i n 
d urati o n. C N V of greater t ha n 2 years si nce cli nical dia g n osis is per mitte d f or u p t o 2 5 % 
of t he t otal patie nt p o p ulati o n. Per mitte d C N V ca n be recei vi n g acti ve treat me nt 
(e. g., a nti-V E G F).  
5. 2. 1. 2  
B ot h E yes 
1 2.  A n y hist or y of or acti ve bacterial, viral, f u n gal, or parasitic i nfecti o n i n eit her e ye i n t he 
3 m o nt hs pri or t o ra n d o mizati o n.  
1 3.  Recei ve d a n y reti nal ste m cell treat me nt.  
1 4.  Pre vi o us partici pati o n i n i nter ve nti o nal cli nical tri als f or G A or dr y A M D, re gar dl ess of 
t he r o ute of a d mi nistrati o n (i.e., oc ular or s yste mic) wit hi n t he last 6 m o nt hs of Da y 1. 
Pri or partici pati o n i n vita mi n a n d mi neral cli nical trials is all o we d at a n y  ti me pri or t o 
Da y 1.   
1 5.  Patie nts w h o  recei v e d pe gcetac o pl a n (als o k n o w n as A P L 2; A p ellis) or a vaci nca pta d 
pe g ol ( als o k n o w n as Zi m ura; I veric Bi o, f or merl y O p ht h otec h) i n eit her e ye are n ot 
eli gi ble f or partici pati o n.  
5. 2. 1. 3  
C o nc urre nt Oc ul ar C o n diti o ns  
1 6.  Reti nal pi g me nt e pit heli u m ( R P E) tear t hat i n v ol ves t he mac ula i n eit her e ye.  
1 7.  Prese nce of a n acti ve oc ular disease i n eit her or b ot h e yes t h at i n t he o pi ni o n of t he 
I n v esti gat or c o m pr o mises or c o nf o u n ds vis ual f u n cti o n, i ncl u di n g b ut n ot li mite d t o, 
u veitis, ot her mac ular dis eases (e. g., cli nicall y si g nifica nt e pireti nal me m bra ne ( E R M), 
f ull t hic k ness mac ular h ole or u nc o ntr olle d gla u c o ma/ oc ular h y perte nsi o n). 
1 8.  Hist or y of i di o pat hic or a ut oi m m u ne- ass ociate d u veitis i n eit her e ye.  
1 9.  Acti ve, i nfecti o us c o nj u n cti vitis, keratitis, scleritis, or e n d o p ht hal mitis i n eit her e ye.  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 2  of 9 6  
2 0.  S p herical e q ui vale nt of t he refracti ve err or i n t he st u d y e ye de m o nstrati n g >  8 di o pters of 
m y o pia ( d eter mi ne a xial le n gt h, e x cl u de if a xial le n gt h > 2 6 m m).  
2 1.  Pr oliferati ve dia betic reti n o pat h y or dia be tic mac ular e de ma i n eit her e ye. 
2 2.  Hist or y of rec urre nt i nf ecti o us or i nfla m mat or y o c ular disease i n eit her e ye. 
N ote:  s u bjects wit h mil d ble p haritis will be all o we d. 
5. 2. 1. 4  
S yste m atic R el ate d  
2 3.  Cli nicall y si g nifica nt me dical or ps yc hiatric c o n diti o ns t hat, i n t he o p i ni o n of t he 
I n v esti gat or, ma ke c o nsiste nt f oll o w- u p o ver t he 1 2- m o nt h treat me nt peri o d u nli kel y, or 
w o ul d ma ke t he s u bject a n u nsafe st u d y ca n di date. 
2 4.  A n y s cree ni n g l a b orat or y val ue ( he mat ol o g y, ser u m c he mistr y or uri nal ysis) t hat i n t he 
o pi ni o n of t he I n v esti gat or is cli nicall y si g nifica nt a n d n ot s uita ble f or st u d y partici pati o n.  
2 5.  Prese nce or treat me nt f or a n y acti ve s yste mic or l o calize d i nfecti o n.   
2 6.  K n o w n aller g y t o c o nstit ue nts of t he st u d y dr u g f or m ulati o n or cli nicall y rele va nt 
se nsiti vit y t o fl u or escei n.  
2 7.  K n o w n si g nifica nt hist or y of dr u g/alc o h ol a b use or a p ositi ve dr u gs of a b us e test at 
scree ni n g t hat c o ul d n ot be e x plai ne d as a p pr o pri ate ma na geme nt of a me dical c o n diti o n . 
( Ca n na bi n oi ds are n ot p art of dr u g scree n). 
2 8.  Hist or y se v ere aller gic or a na p h ylactic reacti o ns t o rec o m bi na nt t hera pe utic pr otei ns, 
f usi o n pr otei ns, or c hi meric, h u ma n, or h u ma nize d a nti b o dies.  
2 9.  Hist or y of m ali g na n c y di a g n os e d o r treate d wit hi n 2 years (rece nt l ocalize d treat me nt of 
s q ua m o us or n o n-i n vasi v e basal cell s ki n ca ncers is per mitte d; cer vical carci n o ma i n sit u 
or breast d uct ular carci n o ma i n sit u is all o we d if a p pr o priatel y treate d wit hi n 2 years pri or 
t o Scree ni n g); su bjects u n der e val u ati o n f or mali g na nc y are n ot eli gi ble. 
5. 3  
C o m p aris o n of I ncl usi o n a n d E xcl usi o n Criteri a b y St u d y E ye vs. 
Fell o w  E ye 
Criteri o n  
St u d y 
E ye  
Fell o w 
E ye  
I ncl usi o n Criteri a / Oc ul ar C o n diti o ns: 
 
 
•  
Sta n dar d l u mi na nce B C V A sc ore of 3 4 letters or better usi n g E T D R S c harts at t he 
starti n g dista nce of 4 meters (a p pr o xi matel y 2 0/ 2 0 0 S nelle n e q ui vale nt  or better ) i n t he 
st u d y e ye 
 
 
•  
W ell -de marcate d G A wit h n o a nat o mical e vi de nce (as assesse d b y F A a n d S D -O C T) of 
c urre nt or pri or C N V  
 
 
•  
Clear oc ular me dia a n d a de q uate p u pil dilatati o n a n d fi xati o n t o per mit g o o d q ualit y 
p h ot o gra p hic i ma gi n g.  
 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 3  of 9 6  
E xcl usi o n Criteri a  / Oc ul ar C o n diti o ns 
 
 
•  
Hist or y of pri or I V T i nj ecti o n, vitrect o m y s ur ger y, s u b mac ul ar s ur ger y, or a n y s ur gical 
i nter ve nti o n f or A M D. A si n gl e I V T i nj ecti o n of a nti-V E G F, if a d mi nistere d greater t ha n 
2 years pri or t o scree ni n g, is p er mitte d. A si n gle i ntra o perati ve a d mi nistrati o n of a 
c ortic oster oi d d uri n g cataract s ur ger y f or c yst oi d mac ular e de ma pr o p h yla xis at least 3 
m o nt hs pri or t o scree ni n g is p er mitte d.  
 
 
•  
G A sec o n dar y t o a c o n diti o n ot her t ha n A M D i n eit her e ye (e. g.,  m o n o ge netic mac ular 
d ystr o p hies li ke Star gar dt disease, c o ne r o d d ystr o p h y,  t o xic mac ul o pat hies). 
 
 
•  
A n y hist or y of or acti ve c h or oi dal ne o vasc ularizati o n ( C N V), base d o n fl u orescei n 
a n gi o gra p h y ( F A) a n d S D -O C T i ma gi n g as assesse d b y t he Ce ntral Rea di n g Ce nter  
 
 
•  
Pre vi o us laser p h ot oc oa g ulati o n f or C N V, dia betic mac ular e de ma ( D M E), reti nal vei n 
occl usi o n a n d pr oliferati ve dia betic reti n o pat h y.  
 
 
•  
I ntra oc ular s ur ger y (i ncl u di n g le ns re place me nt s ur ger y) wit hi n 3 m o nt hs pri or t o 
ra n d o mizati o n. 
 
 
•  
Hist or y of laser t hera p y i n t he mac ular re gi o n.  
 
 
•  
A p ha kia  or a bse nce of t he p osteri or ca ps ule. N ote: yttri u m al u mi n u m gar net ( Y A G) laser 
p osteri or ca ps ul ot o m y f or p osteri or ca ps ule o pacificati o n d o ne at least 6 0 da ys pri or t o 
scree ni n g is n ot e xcl u de d. 
 
 
•  
A n y oc ular c o n diti o n ot her t ha n G A sec o n dar y t o A M D t hat  ma y re q uire s ur ger y or 
me dical i nter ve nti o n (i ncl u di n g le ns re place me nt s ur ger y) d uri n g t he st u d y peri o d or, i n 
t he o pi ni o n of t he I n vesti gat or, c o ul d c o m pr o mise vis ual f u ncti o n d uri n g t he st u d y 
peri o d.  
 
 
•  
A n y c o ntrai n dicati o n t o I V T i nj ecti o n i ncl u di n g c urre nt oc ular or peri oc ular i nfecti o n.  
 
 
•  
A ut oi m m u ne u veitis or scleritis, or c hr o nic i nfla m mat or y dis ease of a nteri or se g me nt, 
i ncl u di n g c hr o nic kerat oc o nj u ncti vitis sicca ( m ore t ha n mil d) or i nfla m mat or y ble p haritis 
( n o ni nfecti o us) of eit her e ye ( greater t ha n mil d se verit y), or c hr o nic i nfla m mat or y 
disease of p osteri or c ha m ber.  
 
 
•  
A n y hist or y of or acti ve C N V less t ha n 2 years i n d urati o n. C N V of > 2 years si nce 
cli nical dia g n osis is per mitte d f or u p t o 2 5 % of t he t otal patie nt p o p ulati o n. P er mitte d 
C N V ca n be recei vi n g acti ve treat me nt (e. g., a nti -V E G F).  
 
 
•  
A n y hist or y of or acti ve bacterial, viral, f u n gal, or parasitic i nfecti o n i n t he 3  m o nt hs 
pri or t o ra n d o mizati o n  
 
 
•  
Recei ve d a n y reti nal ste m cell treat me nt.  
 
 
•  
Pre vi o us partici pati o n i n i nter ve nti o nal cli nical trials f or G A or dr y A M D, e xce pt f or 
vita mi ns a n d mi nerals, re gar dl ess of t he r o ute of a d mi nistrati o n (i.e., oc ular or s yste mic) 
wit hi n t he last 6 m o nt hs of Da y 1.  
 
 
E xcl usi o n C riteri a / C o nc urre nt O c ul ar C o n diti o ns:  
 
 
•  
Reti nal pi g me nt e pit heli u m ( R P E) tear t hat i n v ol ves t he mac ula  
 
 
•  
Prese nce of a n acti ve oc ular disease t hat i n t he o pi ni o n of t he I n vesti gat or c o m pr o mises 
or c o nf o u n ds vis ual f u ncti o n, i ncl u di n g b ut n ot li mite d t o, u veitis, ot her mac ular diseases 
(e. g., cli nicall y si g nifica nt e pir eti nal me m bra ne ( E R M), f ull t hic k ness macular h ole or 
u nc o ntr olle d gla uc o ma/ oc ular h y perte nsi o n ). 
 
 
•  
Hist or y of i di o pat hic or a ut oi m m u ne -ass ociate d u veitis  
 
 
•  
Acti ve, i nfecti o us c o nj u ncti vitis, keratitis, scleritis, or e n d o p ht hal mitis  
 
 
•  
S p herical e q ui vale nt of t he refracti ve err or i n t he st u d y e ye de m o nstrati n g > 8  di o pters of 
m y o pia ( deter mi ne a xial le n gt h, e xcl u de if a xial le n gt h > 2 6 m m).  
 
 
•  
Pr oliferati ve dia betic reti n o pat h y or dia betic mac ular e de ma  
 
 
•  
Hist or y of rec urre nt i nfecti o us or i nfla m mat or y oc ular diseas e. N ote:  s u bj ects wit h mil d 
ble p haritis will be all o we d.  
 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 4  of 9 6  
 
5. 4  
Micr o peri met r y ( M P) Criteri a ( At Selecte d Sites O nl y)  
5. 4. 1  
M P I ncl usi o n Criteri a  
Micr o peri metr y scree ni n g test criteria f or eli gi bilit y:  
1.  M ust be a ble t o detect fi x ati o n tar get.  
2.  T otal ela pse d ti me t o c o m plete t he 1 0 - 2 6 8-p oi nt e x a m is ≤ 3 0 mi n utes i n d urati o n.  
3.  Relia bilit y T est rati o ≤ 2 0 % (false p ositi ve rate).  
4.  A bilit y a n d willi n g n ess t o u n derta ke M P assess m e nt as deter mi ne d b y I n v esti gat or.  
5. 4. 2  
M P E xcl usi o n Criteri a  
1.  I n v esti gat or deter mi nes t hat s u bject is u na ble t o p erf orm t he test relia bl y.  
N ote: dis q ualificati o n fr o m t he micr o peri metr y ass ess me nt d oes n ot e x cl u de a s u bject 
fr o m t he trial partici pati o n if s he/ he q ualifies as p er t he rest of t he st u d y e ntr y criteria. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 5  of 9 6  
6  St u d y Tre at me nt  
6. 1  
Cli nic al S u p plies  
6. 1. 1  
N G M 6 2 1 
N G M 6 2 1 is a n ~ 1 5 0 k D a pr otei n e x presse d 
 
.  
N G M 6 2 1 dr u g pr o d uct will be pr o vi de d as a si n gle use sterile s ol uti o n f or i ntra vitreal 
i njecti o n. It is fille d 
.  
T he tar get e d N G M 6 2 1 c o nce ntrati o n is  
 i n f or m ulati o n b uffer c o ntai ni n g 
 
 
6. 2  
A d mi nistr ati o n/ H a n dli n g/ St or a ge/ Acc o u nt a bilit y  
6. 2. 1  
A d mi nistr ati o n  
6. 2. 1. 1  
N G M 6 2 1 
T he i njecti o n pr oce d ure s h o ul d be carrie d o ut u n der ase ptic c o n diti o ns, wit h ha n d was hi n g, 
a n d t he use of sterile gl o ves a n d a mas k. Sterile p arace ntesis e q ui p me nt s h o ul d be a vaila ble 
s h o ul d it be re q uire d. Please refer t o t he St u d y P har mac y M a n ual f or a d diti o nal detail relate d 
t o a d mi nistrati o n. 
6. 2. 1. 2  
S h a m  
S u bjects ra n d o mize d t o t he c o ntr ol ar ms will recei ve S ha m i njecti o ns Q 4 W or Q 8 W d uri n g 
t he 1 2-m o nt h treat me nt p eri o d a n d will u n der g o t h e sa me assess m e nts as t he N G M 6 2 1 
treat me nt ar m (s ee S O A: Ta ble  4 a n d T a ble  5). 
S ha m i njecti o n is a pr oce d ure t hat mi mics a n i ntra vitreal i njecti o n of N G M 6 2 1, e x ce pt t hat 
t he bl u nt e n d of a n e m pt y s yri n ge is presse d a gai nst a n a nest hetize d e ye i nstea d of a n ee dle 
attac he d t o a N G M 6 2 1 -fille d s yri n ge (see St u d y P har mac y M a n ual f or d etai ls).  
6. 2. 2  
St or a ge a n d St a bilit y 
N G M 6 2 1 vials are t o b e st ore d at 5 ℃ ± 3 ℃ u p o n recei pt a n d s h o ul d b e ke pt i n t heir 
pac ka gi n g u ntil use. F urt her i nstr ucti o ns are i n cl u de d i n t he St u d y P har mac y M a n ual. 
Vials  are p ac ka ge d i n a vials/cart o n c o nfi g urati o n f or cli nical a d mi nistrati o n.  
C CI
C CI
C CI
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 6  of 9 6  
6. 2. 3  
Acc o u nt a bilit y  
T he PI is r es p o nsi ble f or e ns uri n g t h at a c urre nt rec or d of i n ve nt or y/ dr u g acc o u nta bilit y is 
mai ntai ne d. I n ve nt or y r ec or ds m ust be rea dil y a vaila ble f or i ns pecti o n b y t he st u d y m o nit or 
a n d are o p e n t o i ns pecti o n b y r e g ulat or y a ut h orities at a n y ti me.  
U p o n recei pt of t he i n vesti gati o nal dr u g, t he d esi g nate d site pers o n nel will vis uall y i ns pect 
t he s hi p me nt, verif y t he n u m ber a n d c o n diti o n of st u d y dr u g recei ve d, a n d c o nfir m recei pt of 
st u d y dr u g. 
At t he c o m pleti o n of t he st u d y, all u n use d st u d y dr u g s u p plies will be ret ur ne d t o t he S p o ns or 
( or desi g nee) or dis p ose d of b y t he cli nic, per t h e S p o ns or’s ( or desi g nee’s) writte n 
i nstr ucti o ns. 
6. 3  
R a n d o miz ati o n  
After writte n i nf or me d c o nse nt has bee n o btai n e d, all s u bjects will recei ve a s u bject 
i de ntificati o n assi g n e d t hr o u g h t he I nteracti ve Res p o nse Tec h n ol o g y (I R T). 
A s u bject m ust satisf y all eli gi bilit y criteria pri or t o ra n d o mizati o n. As part of t he scree ni n g 
pr ocess, t he ce ntral r ea di n g ce nter ( mas ke d t o s u bject treat me nt assi g n me nt) will e val uate 
F A F, C F P, S D -O C T , a n d F A i ma ges t o pr o vi de a n o bjecti ve, mas ke d ass ess me nt of s u bject 
eli gi bilit y. I n a d diti o n, treat me nt assi g n me nt/re gi me n will be mas ke d  t o t he s pecific site 
pers o n nel, st u d y s u bjects, s p o ns or st u d y tea m, a n d s p o ns or Me dical M o nit or t hr o u g h o ut t he 
st u d y peri o d. After all s u bject eli gi bilit y re q uire m e nts are c o nfir me d, site p ers o n nel will 
c o ntact t he I R T o n D a y 1 visit f or assi g n me nt of t he st u d y treat me nt ( N G M 6 2 1 or S ha m). 
S u bjects will be ra n d o mize d i n a 2: 1: 2: 1 rati o t o o ne of t he st u d y treat me nts ar ms 
( N G M 6 2 1 Q 4 W, S ha m Q 4 W, N G M 6 2 1 Q 8 W, or S ha m Q 8 W). T he ra n d o mizati o n will be 
stratifie d b y s u bj ects’ bas eli ne C N V stat us ( Yes/ N o) i n t he fell o w ( n o n-st u d y) e ye. 
T he  s u bjects will be ra n d o mize d o n t he sa me da y t he st u d y treat me nt is t o be i nitiate d 
( Da y 1 visit).  
6. 3. 1  
M as ki n g  
T his is a d o u ble- mas ke d st u d y. T here m ust be a mi ni m u m of t w o i n vesti gat ors per site t o 
f ulfill t he mas ki n g r e q uir e me nts of this st u d y. St u d y visits m ust be sc he d ul e d w he n b ot h 
i n vesti gat ors are pr ese nt. At least o ne i n vesti gat or will be desi g nat e d as t he e val uati n g 
p h ysicia n w h o will be mas ke d t o s u bjects’ treat me nt assi g n me nt a n d will e val uate all oc ular 
assess me nts. At least o ne ot her i n vesti gat or (a n d d esi g nat e d, u n mas ke d assista nt, as nee de d) 
will be desi g nat e d as t he treati n g (i njecti n g) p h ysi cia n w h o will be u n mas k e d t o s u bjects’ 
treat me nt assi g n me nt a n d will a d mi nister i njecti o ns ( N G M 6 2 1 or S ha m). T he Pri nci pal 
I n v esti gator m ust be mas ke d t o s u bjects’ treat me nt assi g n me nt. All r oles f or eac h st u d y staff 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 7  of 9 6  
me m ber s h o ul d be clearl y d oc u m e nte d o n t he Site Dele gati o n L o g. T he Dele gati o n L o g 
s h o ul d be si g ne d b y t he Pri nci pal I n v esti gat or. 
O nce t he d esi g n ate d mas ke d vs. u n mas ke d r oles are deli neat e d a n d t he site st u d y staff h a ve 
starte d t o perf or m t he m, t he r oles ca n n ot be s witc h e d or re v erse d at a n y ti me d uri n g t h e 
c o n d uct of t he st u d y. I n t he e ve nt a n alter nat e i n vesti gat or nee ds t o be s u bstit ute d f or a n 
i n vesti gat or, t hat alter nat e p h ysici a n ma y ass u me o nl y o ne r ole (i.e., treati n g p h ysicia n or 
e val uati n g p h ysi cia n) f or t he d urati o n of t he st u d y a n d m ust recei v e s p o ns or a p pr o val. I n cas e 
a site is e x perie nci n g u n e x pecte d e xtre me sit uati o ns, t he s p o ns or’s per missi o n mi g ht be 
gr a nt e d t o s witc h a n i n vesti gat or/t he st u d y staff m e m ber fr o m t he m as ke d r ole (e val uati n g 
p h ysicia n) t o t he u n mas k e d r ole (tr eati n g p h ysicia n), b ut n ot t he ot her wa y ar o u n d. 
Starti n g at t he s u bject’s Da y 1 visit, t he treati n g p h ysicia n(s) perf or mi n g t he N G M 6 2 1 or 
S ha m i njecti o ns a n d p ost- treat me nt fi n ger c o u nti n g, m ust c o nti n ue t heir r ol e as treati n g 
p h ysicia n o nl y. T h e y ca n n ot be i n v ol ve d i n a n y ot her as pect of t he st u d y a n d m ust n ot 
di v ul ge treat me nt assi g n me nt t o a n y o n e. S u bjects, st u d y site pers o n n el ( wit h t he e x ce pti o n of 
t he treati n g p h ysicia n[s], assista nt[s], a n d p har macist if a n y), t he d esi g nate d e val uati n g 
p h ysicia n(s), ce ntral r ea di n g ce nter pers o n nel, a n d t he S p o ns or a n d its a ge nts ( wit h t he 
e x ce pti o n of dr u g acc o u nta bilit y m o nit ors) will be mas ke d t o treat me nt assi g n me nt. 
T he V A e x a mi ner ( p erf or mi n g B C V A e x a mi nati o ns a n d rea di n g s p ee d ass ess me nt) will be 
mas ke d t o s u bject treat m e nt assi g n me nt a n d t he treate d st u d y e ye a n d will o nl y perf or m 
B C V A, B C V A u n der l o w l u mi na nce c o n diti o ns ( L L V A), a n d rea di n g s p ee d assess me nts. 
T he B C V A e x a mi ner will ha ve n o access t o t he V A sc ores of a s u bject’s pre vi o us visits. 
T he  V A e x a mi ner is n ot all o we d t o perf or m a n y ot her tas ks i n v ol vi n g direct s u bject care. 
E ver y eff ort m ust be ma d e t o li mit t he n u m ber of u n mas ke d st u d y p ers o n nel t o e ns ure t he 
i nte grit y of t his mas ke d st u d y. T here m ust be n o m ore t ha n fi ve u n mas k e d pers o n nel at a n 
i n vesti gati ve site at o ne ti me. I n s p ecial circ u msta n ces m ore t ha n fi ve u n mas ke d pers o n nel 
ma y b e per mitte d after c o ns ultati o n wit h t he me di cal m o nit or. D oc u me nte d pr oce d ures will 
be p ut i n place t o a v oi d i na d verte ntl y u n mas ki n g st u d y tea m me m bers. O nl y t he I R T 
pr o vi der res p o nsi ble f or verif yi n g a s u bject’s ra n d o mizati o n a n d st u d y treat me nt assi g n me nt, 
w h o are n ot ot her wise i n v ol ve d i n t he st u d y, will ha ve access t o t he u n mas ki n g c o d e. F or t he 
d urati o n of t he st u d y, t h e s u bject treat me nt assi g n me nt will n ot be u n mas ke d u nless re q uire d 
f or s u bject saf et y. 
All st u d y visit assess me nts, e x ce pt t h ose at scree ni n g, s h o ul d be p erf or m e d b y mas ke d site 
pers o n nel o nl y. Starti n g at Da y 1 visit, t he u n mas ke d treati n g p h ysicia n will o nl y p erf or m t he 
st u d y treat me nt a n d p ost-treat me nt visi o n testi n g (fi n ger c o u nti n g a n d, if a p plica ble, ha n d 
m o ve me nt a n d/ or li g ht p erce pti o n). T h e i njecti n g p h ysicia n will als o perf or m i njecti o n f or 
C N V treat me nt as des cri be d i n Secti o n  7. 3. 1 5 . 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 8  of 9 6  
St u d y assess me nts i ncl u d e P K sa m ple c ollecti o n i n all s u bjects ( Secti o n  7. 3. 6 ). 
W hile  P K  sa m ples m ust be c ollecte d fr o m s u bjects assi g ne d t o t he S ha m ar m t o mai ntai n t he 
mas ki n g of tr eat me nt assi g n me nt, P K assa y res ults f or t hese s u bjects are ge nerall y n ot 
nee de d f or t he safe c o n d uct or pr o per i nter pret ati o n of t his st u d y. S p o ns or pers o n nel 
res p o nsi ble f or p erf or mi n g P K assa ys will be u n mas ke d t o s u bjects’ treat me nt assi g n me nts t o 
i de ntif y a p pr o priate P K s a m ples t o be a nal yz e d. Sa m ples fr o m s u bjects assi g ne d t o t he S ha m 
ar m will n ot be a nal yz e d e x ce pt b y re q uest (i.e., t o e val uate a p ossi ble err or i n d osi n g). 
6. 3. 2  
Re m o v al of St u d y M as ki n g (If A p plic a ble) 
U n mas ki n g wi ll be a v aila ble t o t he PI i n t he e ve nt of a me dical e mer ge n c y or a n A E t hat 
necessitate d i de ntificati o n of t he st u d y dr u g f or t h e welfare of t h at s u bject. E x ce pt i n t he case 
of a me dical e mer ge n c y, t he PI a n d cli nic staff will re mai n mas ke d d uri n g t he c o n d uct of t he 
st u d y a n d u ntil s uc h ti me t hat all discre pa n cies i n t he cli nical data b ase are res ol ve d (i.e., at 
t he ti me of t he data bas e l oc k). T he d ate a n d ti me w he n t he PI re m o v e d t he st u d y mas ki n g f or 
a n i n di vi d ual s u bject will be d oc u me nte d, a n d a n otificati o n will be se nt t o t he S p o ns or. 
T he  c o ntracte d C R O’s p har mac o vi gila nce tea m ma y als o be re q uire d t o brea k t he mas k f or 
re g ulat or y r e p orti n g p ur p oses a n d if re q uire d b y l o cal healt h a ut h orities, t he S p o ns or will 
brea k t he tr eat me nt c o d e f or all seri o us, u ne x pecte d s us pecte d a d v erse reacti o ns t hat are 
c o nsi dere d b y t he i n v esti gat or or S p o ns or t o be relate d t o st u d y dr u g. 
6. 4  
C o nc o mit a nt Me dic ati o ns  
A n y me di cati o n (i ncl u di n g oc ul ar) ta k e n at least o nce wit hi n 2 8 da ys pri or t o Scree ni n g Visit 
a n d d uri n g t he st u d y p eri o d as well as t he reas o n f or use will be rec or de d i n t he s o urce 
d oc u me nts a n d t he electr o nic case re p ort f or ms (e C R Fs); ot her t ha n pr ot oc ol- s pecifie d 
pr oce d ur al me dicati o ns ( e. g., dilati n g dr o ps or fl u orescei n d yes) a n d pre- a n d p ost- i njecti o n 
me dicat i o ns (e. g., pr o p ar acai ne or a nti micr o bials [if a p plica ble]) use d b y a s u bject wit hi n 
7 da ys prece di n g Da y 1 visit. S u bjects s h o ul d refrai n fr o m t he use of a n y n e w prescri pti o n 
me dicati o ns or pr o d ucts or c ha n ge i n t he d os e or fre q ue nc y of e xisti n g t hera pies fr o m 
Scree ni n g t o Da y 1 u ntil E O S.  
I n a d diti o n, a n y i n v asi ve oc ular pr o ce d ure fr o m t h e pre vi o us 5 years m ust be rec or de d i n t he 
s o urce d oc u m e nt (i ncl u di n g start a n d st o p dates).  
T he Me dical M o nit or s h o ul d be i nf or me d of c h a n ges or a d diti o n of me dicati o ns d uri n g t his 
ti me peri o d.  
T he f oll o wi n g are pr o hi bite d fr o m wit hi n 5 half-li ves or 9 0 da ys, w hic h e ver is l o n ger, pri or 
t o st u d y e ntr y t hr o u g h t o t he e n d of st u d y: 
•  I n v esti gati o nal a ge nts, ot her t ha n N G M 6 2 1, or de vices f or a n y i n dicati o n  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 4 9  of 9 6  
I n a d diti o n, a ge nts use d f or t he treat me nt of a n y c o n diti o n liste d i n t he e x cl usi o nar y 
e nr oll me nt criteria are pr o hi bite d fr o m 2 8 da ys pri or t o Da y 1 a n d t hr o u g h t he e n d of st u d y. 
N ote: T his list of e x cl u de d me dicati o ns/t hera pies is n ot a n e x ha usti ve list. I n vesti gat or 
j u d ge me nt m ust be use d t o j ustif y i nitiati n g a n y st u d y me dicati o n d uri n g t h e st u d y. 
6. 5  
Per mitte d T her a pies  
S u bjects re q uire d t o use me dicati o ns t hat are pr o hi bite d (see Secti o n  6. 4 ) will n ot be eli gi ble 
f or t he st u d y. S u bjects w h o use ot her mai nte na n ce t hera pies s h o ul d c o nti n u e t heir use. 
Of  n ote, t he f oll o wi n g ar e s o me c o m m o n t hera pi es t hat are per mitte d: 
 
•  O nset of oc ular h y perte nsi o n or gla u c o ma i n t he st u d y e ye d uri n g a s u bject’s st u d y 
partici pati o n s h o ul d be tr ea te d as cli nicall y i n dicat e d. 
•  O nset of cat aract or p osteri or ca ps ular o pacifi cati o n i n eit her e ye d uri n g t h e s u bject’s 
st u d y partici p ati o n ma y b e treate d as cli nicall y i n dicate d. D ose-i nterr u pti o n criteria 
(see Secti o n  6. 7 , Ta bl e  3) ma y a p pl y wit h cataract s ur ger y. 
•  S h ort- ter m use of t o pical c ortic oster oi ds aft er cataract s ur ger y, Y A G ca ps ul ot o m y, or 
peri p her al iri d ot o m y. 
•  Oral c ortic oster oi ds at d oses ≤ 1 0 m g/ da y pre d nis o ne or e q ui vale nt 
6. 6  
Lif est yle C o nsi der ati o ns/ Restricti o ns  
Fe male s u bjects of c hil d beari n g p ote ntial a n d mal e s u bjects wit h a fe m ale part ner of 
c hil d beari n g p ote ntial m ust a gr ee t o eit her be a bsti ne nt or use c o nsiste nt a n d a de q uate birt h 
c o ntr ol fr o m Scree ni n g t o E n d of St u d y ( E O S / Wee k 5 6). O n e of t he f oll o wi n g f or ms of 
c o ntrace pti o n is re q uire d:  
a)  C o n d o m  
b)  H or m o ne- c o nt ai ni n g c o ntrace pti ve  
c)  I ntr a uteri ne d e vice wit h a fail ure rate < 1 % per year  
d)  Cer vical ca p or dia p hr a g m wit h s per mici dal a ge nt  
e)  T u bal sterilizat i o n  
f) Vasect o m y i n male part n er  
6. 7  
Disc o nti n u ati o n of S u bjects fr o m St u d y P a rtici p ati o n  
S u bjects will be i nf or me d t hat t he y are free t o wit h dra w fr o m t he st u d y at a n y ti me a n d f or 
a n y reas o n. T he s u bject ca n als o deci de t o disc o nti n ue st u d y treat me nt b ut c o nti n ue t he 
re mai ni n g st u d y assess me nts / visits (i n t his case t he s u bject w o ul d be desi g nat e d a treat me nt 
disc o nti n uati o n rat her t ha n a st u d y disc o nti n uati o n). T he PI ma y re m o ve a s u bject fr o m t he 
st u d y if, i n t he PI’s o pi ni o n, it is n ot i n t he best i nterest of t he s u bject t o c o nti n ue t he st u d y. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 5 0  of 9 6  
S u bjects ma y be dis c o nti n ue d d ue t o a c h a n ge i n c o m plia nce wit h a n i ncl usi o n/e x cl usi o n 
criteri o n t hat is cli nicall y rele va nt a n d affects s u bj ect safet y, o cc urre n ce of A Es  (Ta ble  3), 
occ urr e nce of pr e g na nc y, or a d mi nistrati o n of n o n- per mitte d c o nc o mita nt me dicati o n t hat 
mi g ht aff ect s u bject s afet y or st u d y ass ess me nts/ o bjecti ves. N otificati o n of disc o nti n uati o n 
will be m a de i m me diatel y t o t he S p o ns or Me dical M o nit or or desi g n ee. I n case of pre mat ure 
disc o nti n uati o n of st u d y partici pati o n, eff orts will be ma de t o perf or m all fi nal E O T 
visit/assess me nts (see Ta ble  4 a n d Ta ble  5). T he d ate t he s u bject is wit h dra w n fr o m t he st u d y 
a n d t he reas o n f or disc o nti n uati o n will be rec or de d o n t he s u bject’s e C R F. All wit h dra w n 
s u bjects will be f oll o we d u ntil res ol uti o n of a n y A Es or u ntil a n y u nres ol ve d A Es are j u d ge d 
b y t he PI t o ha v e sta bilize d.  
T a ble 3. 
D ose  -I nterr u pti o n a n d Tre at me nt Disc onti n u ati o n Criteri a  
E ve nt  
D ose -I nterr u pti o n Criteri a 
I ntra oc ular i nfla m mati o n 
I nterr u pt st u d y treat me nt if i ntra oc ular i nfla m mati o n (iritis, iri d oc yclitis, 
u veitis, or vitritis ) is ≥ 1 + i n t he st u d y e ye (see t he gra di n g sc ales of i ntra oc ular 
i nfla m mati o n i n A p pe n di x 1. S u bj ects wit h ≥ 3 + i ntra oc ular i nfla m mati o n will 
be disc o nti n ue d fr o m t he st u d y treat me nt.  
V A l oss  
I nterr u pt st u d y treat me nt if t here is a treat me nt-relate d decrease i n B C V A of 
≥ 3 0 letters i n t he st u d y e ye c o m pare d wit h t he last assess me nt of B C V A pri or 
t o t he m ost rece nt treat me nt or fr o m baseli ne B C V A at St u d y Da y 1. St u d y 
treat me nt ma y be per mitte d s u bse q ue ntl y as deter mi ne d b y t he S p o ns or a n d 
In vesti gat or.  
E le vate d I O P 
I nterr u pt st u d y treat me nt if I O P i n t he st u d y e ye is ≥ 3 0 m m H g. Treat me nt 
ma y be per mitte d w he n I O P has bee n l o were d t o < 3 0 m m H g, eit her 
s p o nta ne o usl y or b y treat me nt, as deter mi ne d b y t he In vesti gat or.  
Vitre o us he m orr ha ge  
I nterr u pt st u d y treat me nt i n t he e ve nt of a vitre o us he m orr ha ge i n t he st u d y 
e ye. St u d y treat me nt ma y be per mitte d s u bse q ue ntl y as deter mi ne d b y t he 
S p o ns or a n d In vesti gat or . 
R he g mat o ge n o us reti nal 
brea k  
I nterr u pt st u d y treat me nt if a r eti nal brea k is prese nt i n t he st u d y e ye. St u d y 
treat me nt ma y be res u me d n o earlier t ha n 3 0 da ys after s ucc essf ul laser 
reti n o pe x y as deter mi ne d b y t he In vesti gat or.  
R he g mat o ge n o us reti nal 
detac h me nt or mac ular 
h ole  
Disc o nti n ue s u bj ects fr o m st u d y treat me nt f or t he d urati o n of t he st u d y if 
r he g mat o ge n o us reti nal detac h me nt or Sta ge 3 or 4 mac ular h oles is o bser ve d. 
Acti ve l ocal or s yste mic 
i nfecti o n 
I nterr u pt st u d y treat me nt if a n y of t he f oll o wi n g are prese nt: i nfecti o us 
c o nj u ncti vitis, i nfecti o us keratitis, i nfecti o us scleritis, or e n d o p ht hal mitis i n 
eit her e ye or if t he s u bj ect is c urre ntl y recei vi n g treat me nt f or a n acti ve l oc al 
or s yste mic i nfecti o n. S u bj ects wit h e n d o p ht hal mitis i n t he st u d y e ye will be 
disc o nti n ue d fr o m t he st u d y tr eat me nt.  
Cataract s ur ger y i n st u d y 
e ye  
I nterr upt st u d y treat me nt after cataract s ur ger y i n st u d y e ye. St u d y treat me nt 
ma y be res u me d n o earlier t ha n 3 0 da ys after a n u nc o m plicate d cataract 
s ur ger y a n d n o e vi de nce of p ost-o perati o nal i nfla m mati o n. F or cataract s ur ger y 
wit h c o m plicati o ns, st u d y treat me n t ma y be per mitte d as det er mi ne d b y 
S p o ns or a n d In vesti gat or.  
Oral c ortic oster oi ds 
( pre d nis o ne > 1 0 m g/ da y or 
e q ui vale nt  
I nterr u pt st u d y treat me nt. St u d y treat me nt ma y be res u me d w he n oral 
c ortic oster oi ds d osi n g is pre d nis o ne ≤ 1 0 m g/ da y or e q ui vale nt.  
I V c ortic oster oi ds 
I nterr u pt st u d y treat me nt. St u d y treat me nt ma y be res u me d w he n t he s u bj ect 
has fi nis he d I V c ortic oster oi d c o urse a n d oral c ortic oster oi d d osi n g is 
pre d nis o ne ≤ 1 0 m g/ da y or e q ui vale nt.  
B C V A = b est c orrecte d vis ual ac uit y; I O P = i ntra oc ular press ure; I V = i ntra ve n o us; V A = vis ual ac uit y; Y A G = yttri u m al u mi n u m gar net  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 5 1  of 9 6  
If a s u bject misses m ore t ha n 2 d oses of st u d y treat me nt wit hi n a n y 2 4-w ee k treat me nt 
peri o d, t he I n vesti gat or a n d t he S p o ns or ma y c o nsi der disc o nti n ui n g t he s u bject fr o m t he 
st u d y treat me nt. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 5 2  of 9 6  
7  St u d y Pr oce d ures  
7. 1  
Sc he d ule of St u d y Pr oce d ures  
T a b ular s u m maries  of t he assess me nts pla n ne d are  prese nt e d i n Ta ble  4 f or s u bjects i n t he Q 4 
wee ks ar m a n d Ta ble  5 f or s u bjects i n t he Q 8 wee ks ar m. T he d osi n g sc he d ule f or b ot h ar ms 
( N G M 6 2 1 a n d s ha m) is prese nte d i n Ta bl e  6. 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 5 3  of 9 6  
T a ble 4. 
Q 4 Wee k Ar ms Sc he d ule of Assess me nts ( N G M 6 2 1 a n d S h a m)  
St u dy fl o wc h art f or Q 4 W Ar ms: D ay 1, Week 1, Week 4 t hr o u g h Week 5 6 
Acti vit y/  
Assess me nt  
Scree n  B aseli ne  
Tre at me nt  
 
F oll o w 
U p  
D a y -2 8 
t o -3  
D a y 1  W k 1  W k 4  W k 8  W k 1 2  W k 1 6  W k 2 0  W k 2 4  W k 2 8  W k 3 2  W k 3 6  W k 4 0  W k 4 4  W k 4 8  
W k 5 2  
E O T  [ 9] 
W k 5 6  
E O S  
M o nt h  
 
 
 
M 1  
M 2  
M 3  
M 4  
M 5  
M 6  
M 7  
M 8  
M 9  
M 1 0  M 1 1  M 1 2  
M 1 3  
M 1 4  
Visit  Wi n d o ws  
 
 
± 3  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
I nf or me d C o nse nt  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I ncl usi o n/ 
E xcl usi o n criteria  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
De m o gra p hics  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
Oc ular/ Me dical  Hist or y  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P h ysical  E xa m  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
B o d y Wei g ht  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
Pre g na nc y  T esti n g [ 1] 
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
X  
 
Bl o o d Sa m ple 
( He mat ol o g y, 
c he mistr y) [ 2] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Uri ne Sa m ple 
( Uri nal ysis, Dr u g 
Scree n)  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A d verse  E ve nts  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
C o nc o mita nt  Me dicati o ns  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
Vital  Si g ns  
X  
 
 
 
 
 
 
 
X  
 
 
 
 
 
 
X  
X  
F RI I n de x  [ 3] 
 
X  
 
 
 
 
 
 
X  
 
 
 
 
 
 
X  
 
N EI V F Q -2 5 [ 3] 
 
X  
 
 
 
 
 
 
X  
 
 
 
 
 
 
X  
 
B C V A  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
L L V A  
O U  
 
 
 
 
 
 
 
O U  
 
 
 
 
 
 
O U  
 
Rea di n g S pee d  
 
X  
 
 
 
 
 
 
X  
 
 
 
 
 
 
X  
 
Pre - a n d P ost-d ose I O P [ 4] 
O U  
O U  
S E  
S E  
S E  
O U  
S E  
S E  
O U  
S E  
S E  
O U  
S E  
S E  
S E  
O U  
O U  
Slit la m p  Bi o micr osc o p y  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
Dilate d F u n d us E xa m a n d 
I n direct O p ht hal m osc o p y 
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
O U  
S D -O C T  [ 5] 
O U  
 
 
 
 
 
O U  
 
O U  
 
O U  
 
O U  
 
 
O U  
O U  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 5 4  of 9 6  
Acti vit y/  
Assess me nt  
Scree n  B aseli ne  
Tre at me nt  
 
F oll o w 
U p  
D a y -2 8 
t o -3  
D a y 1  W k 1  W k 4  W k 8  W k 1 2  W k 1 6  W k 2 0  W k 2 4  W k 2 8  W k 3 2  W k 3 6  W k 4 0  W k 4 4  W k 4 8  
W k 5 2  
E O T  [ 9] 
W k 5 6  
E O S  
M o nt h  
 
 
 
M 1  
M 2  
M 3  
M 4  
M 5  
M 6  
M 7  
M 8  
M 9  
M 1 0  M 1 1  M 1 2  
M 1 3  
M 1 4  
Visit  Wi n d o ws  
 
 
± 3  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
± 5  
F u n d us A ut ofl u oresce nce 
( F A F) [ 6] 
O U  
 
 
 
 
 
 
 
O U  
 
 
 
 
 
 
 O U  
 
Fl u orescei n a n gi o gra p h y 
( F A) [ 5] 
O U  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C ol or F u n d us 
P h ot o gra p h y ( C F P)  
O U  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
O U  
 
Micr o peri metr y  at select 
sites ( St u d y e ye o nl y) [ 7] 
S E  
S E  
 
 
 
 
 
 
S E  
 
 
 
 
 
 
S E  
 
Ser u m P K [ 8] 
 
X  
X  
X  
 
 
X  
 
X  
 
 
 
X  
 
X  
X  
X  
Ser u m  A D A [8] 
 
X  
  
X  
 
 
X  
 
X  
 
 
 
X  
 
X  
X  
X  
Ser u m N A b [ 8] 
 
X  
 
X  
 
 
X  
 
X  
 
 
 
X  
 
X  
X  
X  
Ser u m  –  C3 a nd C H 5 0  
 
X  
X  
X  
 
 
 
 
X  
 
 
 
 
 
 
X  
X  
Ra n d o mizati o n  
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
D osi n g ( Please see  T a ble  6 ) 
 
O U  = b ot h  e yes; S E  = st u d y e ye; X = Re q uire d . 
[ 1] Fe males of c hil d beari n g p ote ntial o nl y; Ser u m pre g na nc y test t o be c o n d ucte d at scree ni n g. Uri ne pre g na nc y test t o be c o n d uct e d o n Da y 1 a n d Wee k 5 2  visit. If 
pre g na nc y is s us pecte d, a ser u m pre g na nc y test ma y be c o n d ucte d.  
[ 2] F or t he scree ni n g visit o nl y, it is all o wa ble t o dra w bl o o d i n t he or der of assess me nts as liste d i n t he ta ble O R t he bl o o d d ra w ca n occ ur ri g ht bef ore t he F A 
assess me nt t o all o w f or a si n gl e nee dle stic k.  
[ 3] T he patie nt -re p orte d o utc o me ( P R O) meas ures (N EI V F Q -2 5 a n d F RI I n de x) will be a d mi nistere d b y t he mas ke d sit e staff (e xce pt f or t he V A e xa mi ner) pri or 
t o a n y ot her visit assess me nts bei n g perf or me d. 
[ 4] Refere nce Secti o n  7. 3. 1 2. 1  a n d t he p har mac y ma n ual f or details.  
[ 5] A F A a n d S D -O C T s h o ul d be perf or me d if t he de vel o p me nt of C N V is s us pecte d i n st u d y e ye. T he ce ntral rea di n g ce nter m ust c o nfir m t his fi n di n g bef ore a n y 
i nter ve nti o n is i nitiate d. See S ecti o n  7. 3. 1 5  f or details. 
[ 6] After ra n d o mizati o n, if a patie nt misses a st u d y visit w he n F A F  i ma ges were sc he d ule d t o be ta ke n, t he i ma ges s h o ul d be ta ke n at t he ne xt sc he d ule d visit. 
C CI
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 5 7  of 9 6  
[ 1] Fe males of c hil d beari n g p ote ntial o nl y; Ser u m pre g na nc y test t o be c o n d ucte d at scree ni n g. Uri ne pre g na nc y test t o be c o n d uct e d o n Da y 1 a n d Wee k 5 2  visit. 
If pre g na nc y is s us pecte d, a ser u m pre g na nc y test ma y be c o n d ucte d.  
[ 2] F or t he scree ni n g visit o nl y, it is all o wa ble t o dra w bl o o d i n t he or der of assess me nts as liste d i n t he ta ble O R t he bl o o d dra w ca n occ ur ri g ht bef ore t he F A 
assess me nt t o all o w f or a si n gl e nee dle stic k.  
[ 3] C ol u m ns s ha de d gra y i n dic ate t hat a d verse e ve nt re p orti n g will be b y tele p h o ne ( 
) f or n o n-visit m o nt hs ( W ee ks 1 2, 2 0, 2 8, 3 6, a n d 4 4) f or s u bj ects i n t he 
Q 8 W ar m o nl y.  
[ 4] T he patie nt -re p orte d o utc o me ( P R O) meas ures ( N EI V F Q-2 5 a n d F RI I n de x) will be a d mi nistere d b y t he mas ke d sit e staff  (e xce pt f or t he V A e xa mi ner) pri or 
t o a n y ot her visit assess me nts bei n g perf or me d. 
[ 5] Refere nce Secti o n  7. 3. 1 2. 1  a n d t he p har mac y ma n ual f or details.  
[ 6] A F A a n d S D -O C T s h o ul d be perf or me d  if t he de vel o p me nt of C N V is s us pecte d i n st u d y e ye. T he ce ntral rea di n g ce nter m ust c o nfir m t his fi n di n g bef ore a n y 
i nter ve nti o n is i nitiate d. See S ecti o n  7. 3. 1 5  f or details. 
[ 7] After ra n d o mizati o n, if a patie nt misses a st u d y visit w he n F A F i ma ges were sc he d ule d t o be ta ke n, t he i ma ges s h o ul d be  ta ke n at t he ne xt sc he d ule d visit. 
[ 8]  Micr o peri metr y is o pti o nal a n d a p plies t o select sites.  
[ 9] P K, anti -dr u g a nti b o d y a n d ne utralizi n g a nti b o d y sa m ples will be c ollecte d at Da y 1 pre -d ose , at W ee k 1  p ost -d ose ( P K c ollecti o n o nl y), W ee k 4 p ost -d ose , 
W ee k s 8, 1 6, 2 4, 4 0, 4 8  pre -d ose, a n d  o n W ee k s 5 2  a n d 5 6 .  
[ 1 0] F or s u bj ects w h o disc o nti n ue earl y fr o m t he st u d y, t he E O T visit assess me nts s h o ul d be perf or me d after a mi ni m u m of 2 8 da ys h as ela pse d fr o m t he last 
a d mi nistere d d ose. See Secti o n  6. 7  f or details. 
[ 1 1] F or  s u bj ects w h o c o nse nte d t o t he o pti o nal sa m ple c ollecti o n. 
 
 
T a ble 6.  
D osi n g Tre at me nt A r ms ( N G M 6 2 1 a n d S h a m) 
Tre at me nt Ar m  
Scree n  B aseli ne  
Tre at me nt  
 
F oll o w U p  
D a y -2 8 t o  
-3  
D a y 1  
W k 1  W k 4  W k 8  
W k 
1 2  
W k 
1 6  
W k 
2 0  
W k 
2 4  
W k 
2 8  
W k 
3 2  
W k 
3 6  
W k 
4 0  
W k 
4 4  
W k 
4 8  
W k 5 2  
E O T  
 
W k 5 6  
E O S  
N G M 6 2 1 1 5 m g Q 4 W  
 
X [ 1] 
 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
  
 
S ha m Q 4 W  
 
X [ 1] 
 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
X [ 1] 
 
 
N G M 6 2 1 1 5 m g Q 8 W  
 
X [ 1] 
 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
 
S ha m Q 8 W  
 
X [ 1] 
 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
X [ 1] 
 
 
[ 1] Refer t o Secti o n  7. 3. 1 2. 1  a n d  t he p har mac y ma n ual f or details o n treat me nt a d mi nistrati o n a n d pre- a n d post -d ose I O P m o nit ori n g, a n d if nee de d, I O P ma na ge me nt 
i nstr ucti o ns.  
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 5 8  of 9 6  
7. 2  
St u d y Visit Pr oce d ures  
7. 2. 1  
Scree ni n g ( D a y – 2 8 t o D a y  –3) Visit  
T he f oll o wi n g pr oce d ures will be perf or me d at Scree ni n g:  
•  O btai n i nf or me d c o nse nt  
•  I n cl usi o n/e x cl usi o n criteria assess me nt  
•  De m o gra p hics  
•  Oc ular a n d m e dical hist or y  
•  P h ysical E x a m  
•  Meas ure b o d y wei g ht  
•  Ser u m pre g na n c y test f or fe male s u bjects of c hil d -beari n g p ote ntial  
•  He mat ol o g y, C he mistr y  
•  Uri nal ysis  
•  Uri ne dr u g scree n  
•  C ollect a d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  Meas ure  vital si g ns (i ncl u di n g te m perat ure, res pirat or y rate, a n d seat e d bl o o d press ure 
a n d p ulse) 
•  B C V A o n b ot h e yes 
•  L L V A o n b ot h e yes 
•  I ntr a oc ular press ure o n b ot h e yes 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes  
•  S D - O C T o n b ot h e yes 
•  F u n d us a ut ofl u or esce n ce o n b ot h e yes 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 5 9  of 9 6  
•  Fl u orescei n a n gi o gra p h y o n b ot h e yes  
•  C ol or f u n d us p h ot o gr a p h y o n b ot h e yes 
•  Micr o peri metr y ( at selecte d sites) o n st u d y e ye  
•  Sc he d ule Da y 1 visit 
7. 2. 2  
B aseli ne ( D a y 1) Tre at me nt Visit  
T he f oll o wi n g p r oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  Uri ne pre g n a nc y test f or fe male s u bjects of c hil d - beari n g p ote ntial. If pre g na nc y is 
s us pecte d, a s er u m pre g n a nc y test ma y be c o n d uct e d 
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  F RI I n de x  
•  N EI V F Q - 2 5  
•  B C V A o n b ot h e yes 
•  Meas ure rea di n g s p ee d  
•  I ntr a oc ular press ure o n b ot h e yes ( pri or t o dilati n g e yes)  
•  Slit la m p bi o micr osc o p y o n b ot h e yes  
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes  
•  Micr o peri metr y ( at selecte d sites) o n st u d y e ye  
•  Ser u m sa m ple f or P K  
•  Ser u m sa m ples f or A D A a n d N A b 
•  Ser u m sa m ple f or C 3 a n d C H 5 0  
•  
 
•  
  
•  Ra n d o mize a n d d ose all s u bjects ( Q 4 W a n d Q 8 W), as ra n d o mize d 
C CI
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 0  of 9 6  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost- d ose o n b ot h e yes  
•  I O P p ost- d ose o n b ot h e yes 
•  Sc he d ule t he ne xt st u d y visit  
7. 2. 3  
Wee k 1 ( ± 3 d a ys) Visit  
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes  
•  Ser u m sa m ple f or P K  
•  Ser u m sa m ple f or C 3 a n d C H 5 0.  
•  
 
•  
  
•  Sc he d ule t he ne xt st u d y visit 
7. 2. 4  
Wee k 4 ( ±  5 d a ys) Tre at me nt Visit  
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
C CI
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 1  of 9 6  
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes  
•  Ser u m sa m ple f or P K  
•  Ser u m sa m ples f or A D A a n d N A b 
•  Ser u m sa m ple f or C 3 a n d C H 5 0  
•  
 
•  
  
•  D ose Q 4 W s u bjects O N L Y, as ra n d o mize d 
P O S T -D O S E ( O nl y Q 4 W ar ms)  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost- d ose o n st u d y e ye  
•  I O P o n st u d y e ye 
•  Sc he d ule t he ne xt st u d y visit  
7. 2. 5  
Wee k 8 ( ±  5 d a ys) Tre at me nt Visit  
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes  
•  Ser u m sa m ple f or P K ( Q 8 W ar ms o nl y) 
•  Ser u m sa m ples f or A D A a n d N A b ( Q 8 W ar ms o nl y) 
•  D ose all s u bjects ( Q 4 W a n d Q 8 W), as ra n d o mize d  
C CI
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 2  of 9 6  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost d ose o n st u d y e ye 
•  I O P p ost- d ose o n st u d y e ye  
•  Sc he d ule t he ne xt st u d y visit  
7. 2. 6  
Wee k 1 2 ( ± 5 d a ys) Tre at me nt Visit ( Q 4 W A r ms O N L Y)  
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n b ot h e yes ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes 
•  D ose Q 4 W s u bjects O N L Y, as ra n d o mize d  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost d ose o n b ot h e yes  
•  I O P p ost- d ose o n b ot h e yes.  
•  Sc he d ule t h e ne xt st u d y visit  
7. 2. 6. 1  
Wee k 1 2 ( ± 5 d a ys) Tele p h o ne S afet y Visit  ( Q8 W Ar ms O N L Y)  
•  T he sites will c o ntact s u bjects i n t he Q 8 W treat me nt ar m via a tele p h o n e call t o rec or d 
a d verse e ve nts a n d c o nc o mita nt me dicati o ns.  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 3  of 9 6  
7. 2. 7  
Wee k 1 6 ( ± 5 d a ys) Tre at me nt Visit 
T he f oll o w i n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns.  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes  
•  S D - O C T o n b ot h e yes 
•  Ser u m sa m ple f or P K  
•  Ser u m sa m ples f or A D A a n d N A b 
•  D ose all s u bjects ( Q 4 W a n d Q 8 W), as ra n d o mize d.  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost- d ose o n st u d y e ye  
•  I O P p ost d ose o n st u d y e ye  
•  Sc he d ule t he ne xt st u d y visit 
7. 2. 8  
Wee k 2 0 ( ± 5 d a ys) Tre at me nt Visit ( Q 4 W A r ms O N L Y) 
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 4  of 9 6  
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes 
•  D ose Q 4 W s u bjects O N L Y, as ra n d o mize d  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost d ose o n st u d y e ye  
•  I O P p ost- d ose o n st u d y e ye  
•  Sc he d ule t he ne xt st u d y visit  
7. 2. 8. 1  
Wee k 2 0 ( ± 5 d a ys) Tele p h o ne S afet y Visit ( Q 8 W Ar ms O N L Y) 
•  T he sites will c o ntact s u bjects i n t he Q 8 W treat me nt ar m via a tele p h o n e call t o rec or d 
a d verse e ve nts  a n d c o nc o mita nt me dicati o ns.  
7. 2. 9  
Wee k 2 4 ( ± 5 d a ys) Tre at me nt Visit 
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  Vital si g ns (i ncl u di n g te m perat ure, res pirat or y rat e, a n d seat e d bl o o d press ure a n d p ulse) 
•  F RI I n de x  
•  N EI V F Q - 2 5 
•  B C V A o n b ot h e yes  
•  L L V A o n b ot h e yes  
•  Rea di n g s p ee d  
•  I O P o n b ot h e yes ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes 
•  S D - O C T o n b ot h e yes  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 5  of 9 6  
•  F u n d us a ut ofl u or esce n ce o n b ot h e yes 
•  Micr o peri metr y ( at selecte d sites) o n st u d y e ye  
•  Ser u m sa m ple f or P K  
•  Ser u m sa m ples f or A D A a n d N A b 
•  Ser u m sa m ple f or C 3 a n d C H 5 0  
•  
 
•  
  
•  D ose all s u b jects ( Q 4 W a n d Q 8 W), as ra n d o mize d  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost- d ose o n b ot h e yes  
•  I O P p ost- d ose o n b ot h e yes  
•  Sc he d ule t he ne xt st u d y visit  
7. 2. 1 0  
Wee k 2 8 ( ± 5 d a ys) Tre at me nt V isit ( Q 4 W A r ms O N L Y) 
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns.  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes 
•  D ose Q 4 W s u bjects O N L Y, as ra n d o mize d  
C CI
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 6  of 9 6  
P O S T D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost d ose o n st u d y e ye  
•  I O P p ost- d ose o n st u d y e ye  
•  Sc he d ule t he ne xt st u d y visit  
7. 2. 1 0. 1  
Wee k 2 8 ( ± 5 d a ys) Tele p h o ne S afet y Visit ( Q 8 W Ar ms O N L Y) 
•  T he sites will c o ntact s u bjects i n t he Q 8 W treat me nt ar m via a tele p h o n e call t o rec or d 
a d verse e ve nts a n d c o nc o mita nt me dicati o ns.  
7. 2. 1 1  
Wee k 3 2 ( ± 5 d a ys) Tre at me nt Visit 
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes 
•  S D - O C T o n b ot h e yes 
•  D ose all s u bjects ( Q 4 W a n d Q 8 W), as ra n d o mize d  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost d ose o n st u d y e ye  
•  I O P p ost- d ose o n st u d y e ye  
•  Sc he d ule t he ne x t st u d y visit  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 7  of 9 6  
7. 2. 1 2  
Wee k 3 6 ( ± 5 d a ys) Tre at me nt Visit ( Q 4 W A r ms O N L Y) 
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n b ot h e yes ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes 
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost- d ose o n b ot h e yes  
•  I O P p ost- d ose o n b ot h e yes  
•  Sc he d ule t he ne xt st u d y visit  
7. 2. 1 2. 1  
Wee k 3 6 ( ± 5 d a ys) Tele p h o ne S afet y Visit ( Q 8 W Ar ms O N L Y) 
•  T he sites will c o ntact s u bjects i n t he Q 8 W treat me nt ar m via a tele p h o n e call t o rec or d 
a d verse e ve nts a n d c o nc o mita nt me dicati o ns.  
7. 2. 1 3  
Wee k 4 0 ( ± 5 d a ys) Tre at me nt Visit 
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes 
•  S D - O C T o n b ot h e yes  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 8  of 9 6  
•  Ser u m sa m ple f or P K  
•  Ser u m sa m ples f or A D A a n d N A b 
•  D ose Q 4 W & Q 8 W s u bjects, as ra n d o mize d  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost d ose o n st u d y e ye  
•  I O P p ost d ose o n st u d y e ye  
•  Sc he d ule t he ne xt st u d y visit 
7. 2. 1 4  
Wee k 4 4 ( ± 5 d a ys) Tre at me nt Visit ( Q 4 W A r ms O N L Y) 
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes 
•  D ose Q 4 W s u bjects O N L Y, as ra n d o mize d  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost- d ose o n st u d y e ye 
•  I O P p ost- d ose o n st u d y e ye  
•  Sc he d ule t he ne xt st u d y visit  
7. 2. 1 4. 1  
Wee k 4 4 ( ± 5 d a ys) Tele p h o ne S afet y Visit ( Q 8 W Ar ms O N L Y) 
•  T he sites will c o ntact s u bjects i n t he Q 8 W treat me nt ar m via a tele p h o n e call t o rec or d 
a d verse e ve nts a n d c o nc o mita nt me dicati o ns.  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 6 9  of 9 6  
7. 2. 1 5  
Wee k 4 8 ( ± 5 d a ys) Tre at me nt Visit 
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d at Wee k 4 8:  
P R E -D O S E  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  B C V A o n b ot h e yes  
•  I O P o n st u d y e ye ( pri or t o dilati n g e ye) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes 
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes  
•  Ser u m sa m ple f or P K  
•  Ser u m sa m ples f or A D A a n d N A b 
•  D ose Q 4 W & Q 8 W s u bjects, as ra n d o mize d  
P O S T -D O S E  
•  Le v el of visi o n (i ncl u di n g fi n ger c o u nti n g, ha n d m oti o n, a n d li g ht perce pti o n) wit hi n 
1 5 mi n utes p ost- d ose o n st u d y e ye  
•  I O P p ost- d ose o n st u d y e ye  
•  Sc he d ule t he ne xt st u d y visit  
7. 2. 1 6  
Wee k 5 2 ( ± 5 d a ys) – E n d of Tre at me nt ( E O T) Visit ( als o E arl y 
Ter mi n ati o n visit f or a n y s u bjects t h at disc o nti n ue bef ore w ee k 5 2)  
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
•  De m o gra p hics  
•  P h ysical e x a m  
•  Meas ure b o d y wei g ht   
•  Uri ne pre g n a nc y test f or fe male s u bjects of c hil d - beari n g p ote ntial. If pre g na nc y is 
s us pecte d, a s er u m pre g n a nc y test ma y be c o n d uct e d. 
•  He mat ol o g y, C he mistr y  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 0  of 9 6  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
•  Meas ure  vital si g ns (i ncl u di n g te m perat ure, res pirat or y rate, a n d seat e d bl o o d press ure 
a n d p ulse)  
•  F RI I n de x  
•  N EI V F Q - 2 5 
•  B C V A o n b ot h e yes  
•  L L V A o n b ot h e yes  
•  Rea di n g s p ee d  
•  I O P o n b ot h e yes ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes  
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes  
•  S D - O C T o n b ot h e yes 
•  F u n d us a ut ofl u or esce n ce o n b ot h e yes  
•  C ol or f u n d us p h ot o gr a p h y o n b ot h e yes  
•  Micr o peri metr y ( at selecte d sites) o n st u d y e ye  
•  Ser u m sa m ple f or P K  
•  Ser u m sa m ples f or A D A a n d N A b  
•  Ser u m sa m ple f or C 3 a n d C H 5 0  
•  
 
•  
 
7. 2. 1 7  
Wee k 5 6 ( ± 5 d a ys) – F oll o w u p a n d E n d of St u d y Visit  
T he f oll o wi n g pr oce d ures/assess me nts will be perf or me d:  
•  A d verse e ve nts a n d c o nc o mita nt me dicati o ns  
C CI
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 1  of 9 6  
•  Meas ure  vital si g ns (i ncl u di n g te m perat ure, res pirat or y rate, a n d seat e d bl o o d press ure 
a n d p ulse) 
•  B C V A o n b ot h e yes  
•  I O P o n b ot h e yes ( pri or t o dilati n g e yes) 
•  Slit la m p bi o micr osc o p y o n b ot h e yes  
•  Dilate d f u n d us e x a m a n d i n direct o p ht hal m osc o p y o n b ot h e yes 
•  S D - O C T o n b ot h e yes 
•  Ser u m sa m ple f or P K  
•  Ser u m sa m ples f or A D A a n d N A b  
•  If patie nt c o nse nt e d t o t he o pti o nal b uccal s w a b a n d it was n ot c ollecte d at a pri or visit, 
please c ollect t he sa m ple  
•  T his visit mar ks t he e n d of st u d y partici pati o n f or all s u bjects  
7. 3  
St u d y Assess me nts a n d E v al u ati o ns  
7. 3. 1  
De m o gr a p hic/ Oc ul ar C h ar acteristics  
De m o gra p hic c har acteristics i ncl u di n g se x, a ge, race, a n d et h nicit y a n d oc ular c haract eristics 
s uc h as e ye/iris c ol or will be rec or de d ( Ta ble  4 a n d Ta ble  5).  
7. 3. 2  
Oc ul ar/ Me dic al a n d S ur gic al Hist or y  
T he I n vesti gat or or d esi g nee will c ollect a c o m plete oc ular, me dical , a n d s ur gical hist or y 
(Ta ble  4 a n d T a ble  5). S m o ki n g hist or y will be c ollecte d.  
7. 3. 3  
B o d y W ei g ht 
B o d y wei g ht will be c oll ecte d as d eter mi ne d b y t h e Sc he d ule of St u d y Pr oce d ures ( T a ble  4 
a n d Ta ble  5). 
7. 3. 4  
Vit al Si g ns  
Vital si g ns assess me nts will i ncl u de te m perat ure ( C°), res pirat or y rate ( breat hs per mi n ute), 
s yst olic a n d diast olic bl o o d press ure ( m m H g) a n d p ulse rate ( b p m). Bl o o d press ure a n d p ulse 
rate will be meas ure d aft er t he s u bject h as bee n resti n g q uietl y i n a s eate d p ositi o n f or at least 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 2  of 9 6  
5 mi n utes. A n y cli nicall y si g nifica nt a b n or mal vital si g n ass ess me nt re q uires at least o ne 
re peat meas ure m e nt. 
Vital si g ns a b n or malities t hat ( 1) ar e c o nsi dere d cli nicall y si g nifica nt i nitiall y a n d o n 
c o nfir mati o n, ( 2) r e q uire a s u bject t o be disc o nti n u e d fr o m t he st u d y, or ( 3) re q uire a s u bject 
t o recei ve treat me nt will be rec or de d as A Es. 
7. 3. 5  
P h ysic al E x a mi n ati o n 
A f oc use d p h ysical e x a mi nati o n of s pecific b o d y s yste m(s) relati n g t o a n y prese nti n g 
pr o ble m or c urre nt c o n cer n(s) of t he s u bject will be c o n d ucte d. T his ma y i n v ol ve o ne or 
m ore b o d y s yst e m. A n e ye e x a m i ncl u di n g E O M m o ve me nts will be perf or me d, a n d 
a b n or mal fi n di n gs will be car ef ull y d oc u me nte d i n t he s u bject’s e C R F. A n a b n or mal p h ysical 
e x a mi nati o n fi n di n g t hat is c o nsi d ere d cli nicall y si g nifica nt a n d re q uires t he s u bject t o be 
disc o nti n ue d fr o m t he st u d y or re q uires i nter ve nti o n will be rec or d e d as a n A E. 
7. 3. 6  
Cli nic al L a b or at or y E x a mi n ati o ns 
At t he sc he d ule d visit, s peci me ns s h o ul d be c ollecte d pri or t o st u d y e ye treat me nt a n d 
F A F  assess me nts (if a p plica ble). T h e s peci me ns will be f or war d e d t o t he ce ntral la b orat or y. 
T he  ce ntr al la b orat or y will eit her perf or m t he a nal ysis or f or war d s a m ples t o S p o ns or or its 
desi g nee f or a nal ysis a n d/ or st ora ge. 
T he La b or at or y Ma n ual will c o ntai n t he necess ar y i nstr ucti o ns f or o btai ni n g, pr o cessi n g, 
st ori n g a n d s hi p pi n g of all sa m ples. Cli nical la b orat or y kits will be pr o vi de d t o sites b y t he 
ce ntral la b orat or y.  
T he f oll o wi n g assess me nts will be perf or me d as i n dicate d:  
•  He mat ol o g y: h e m o gl o bi n, he mat ocrit, q ua ntitati ve platelet c o u nt, re d bl o o d cell c o u nts, 
w hite bl o o d cell c o u nts, a n d differe ntials, i ncl u di n g ne utr o p hils, ba n ds, l y m p h oc ytes, 
bas o p hils, e osi n o p hils, a n d m o n oc ytes (a bs ol ute) 
•  C he mistr y: s o di u m, p otassi u m, c hl ori de, bicar b o n ate, gl uc ose, bl o o d urea nitr o ge n, 
creati ni ne, calci u m, p h os p h or us, t otal a n d direct bilir u bi n, t otal pr otei n, al b u mi n, 
as partate a mi n otra nsferas e, ala ni ne a mi n otra nsferase, lactate d e h y dr o ge n ase, al kali ne 
p h os p hatase, a n d uric aci d 
•  Uri nal ysis: p H, s pecific gra vit y, gl uc os e, ket o nes, bilir u bi n, pr otei n, ur o bili n o ge n a n d 
micr osc o pic e x a mi nati o n  
•  I nitial ser u m pre g na n c y t est ( β- h u ma n c h ori o nic g o na d otr o pi n) f or w o m e n of 
c hil d beari n g p ote ntial, i n cl u di n g t h ose w h o h a ve h a d t u bal li gati o n. If p ositi ve, st u d y 
treat me nt will n ot be a d mi nistere d. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 3  of 9 6  
•  Uri ne pre g n a nc y test pri or t o eac h st u d y treat me nt f or w o me n of c hil d beari n g p ote ntial, 
i ncl u di n g t h ose w h o ha v e ha d t u bal li gati o n. If p ositi ve, perf or m t he ser u m pre g na nc y 
test. If t h e ser u m pr e g na n c y t est is p ositi ve, d o n ot a dmi nister t he st u d y treat me nt.  
•  Uri ne dr u g scree n assess me nt  
•  C o m ple me nt pat h wa y assess me nt assa y ( C 3 a n d C H 5 0): I n all s u bjects ser u m sa m ples 
will be c ollecte d as o utli ne d  i n Ta ble  4 a n d T a ble  5.  
•  S yste mic P K, A D A, a n d N A b E val uati o n: Ser u m sa m ples f or P K, A D A, a n d N A b will be 
c ollecte d as o utli ne d i n T a ble  4 a n d Ta bl e  5. Pr ocessi n g, st ora ge, a n d s hi p pi n g 
i nstr ucti o ns f or t hese P K bl o o d sa m ples will be prese nte d i n t he st u d y La b Ma n ual.  
•  
 
  
•  If t he s u bject ga v e c o ns e nt f or a n y re m ai ni n g bl o o d (i ncl u di n g plas ma a n d ser u m) 
sa m ples t o be retai ne d f or o pti o nal researc h, t he n t he sa m ples ma y be st ore d f or u p t o 
1 5 years after t he d ate of fi nal cl os ure of t h e ass oci ate d cli nical data b ase.  
7. 3. 7  
B C V A/ L L V A  
Best c orrecte d vis ual ac uit y will be meas ure d b y trai ne d a n d certifie d p ers o n nel at t he st u d y 
sites. T he vis ual ac uit y ( V A) e x a mi ner m ust be mas ke d t o eac h s u bject’s st u d y (treate d) e ye 
a n d treat me nt ar m (st u d y d r u g vs. S ha m) assi g n m e nt. V A will be meas ure d at t he i nter vals 
s pecifie d i n Ta ble  4 a n d Ta ble  5.  
T he na me a n d certificati o n n u m ber of t he visi o n e x a mi ner s h o ul d be d oc u me nte d i n t he 
s u bject’s vis ual ac uit y ( V A) w or ks heet ( pr o vi de d b y t he S p o ns or or d esi g n ee) at eac h visit. 
Retr oill u mi na te d E T D R S c harts are use d i n t his trial. Refracti o n s h o ul d be c o n d ucte d pri or t o 
vis ual ac uit y testi n g t o o btai n best -c orrecte d visi o n. Best -c orrecte d vis ual ac uit y at a starti n g 
dista nce of 4 meters is meas ure d at all  office -bas e d  st u d y visits usi n g sta n dar d c harts, 
li g hti n g, a n d pr oce d ures. T he l o w l u mi na nce vis ual ac uit y ( L L VA) h as t he sa me 
re q uire me nts as t h e best c orrecte d vis ual ac uit y; h o we ver, t he l o w l u mi na nce vis ual ac uit y 
will be meas ure d b y placi n g a 2. 0- l o g- u nit ne utral de nsit y filter o v er t he b est c orrecti o n f or 
t hat e ye a n d h a vi n g t h e p artici pa nt rea d t he n or mall y ill u mi nate d Earl y Treat me nt Dia betic 
Reti n o pat h y St u d y c hart. 
A descri pti o n of t he V A assess me nt is detaile d i n t he St u d y Pr oce d ure Ma n ual or e q ui vale nt. 
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 4  of 9 6  
7. 3. 8  
Re a di n g S pee d  
7. 3. 8. 1  
T he Mi n nes ot a  L o w-Visi o n Re a di n g Test ( M N Re a d)  
T he Mi n nes ota L o w- Visi o n Rea di n g T est ( 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 m al 
a n d l o w- visi o n s u bjects. T he 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 ulat e 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 e C R F a n d 
will n ot be calc ulate d b y t he i nter vie wers. F or a d diti o nal details see t he St u d y Pr oce d ure 
Ma n ual or e q ui val e nt. 
7. 3. 8. 2  
R a d ner Re a di n g C ar ds  
T he Ra d ner Rea di n g Car ds c o nsist of “se nte nce o pt ot y pes,” w hic h are o pti mize d rea di n g test 
ite ms, sta n dar dize d b y c o nstr ucti o n a n d statistical selecti o n. T he Ra d ner Rea di n g Car ds are 
s uita ble f or meas uri n g rea di n g s pee d, rea di n g vis ual ac uit y, a n d critical pri nt size. 
T he  Ra d ner Rea di n g Car ds are i n t he f or m of a letter -size d b o o klet wit h t he rea di n g car ds 
a n d i ncl u des clear i nstr ucti o ns a n d e val uati o n s heets. Ei g ht se nte nces are pri nte d per pa ge. 
Eac h se nte n ce of 1 4 w or ds is pri nte d o n t hree li nes a n d pri nt sizes var y fr o m 6. 3 M t o 0. 2 5 M 
( 2 0/ 4 0 0 t o 2 0/ 1 6 at 3 2 c m). F or a d diti o nal det ails see t he St u d y Pr o ce d ure Ma n ual or 
e q ui vale nt. 
7. 3. 9  
F RI I n de x  
T he F RI I n d e x is a 7 -ite m, i nter vie wer-a d mi nistere d asses s me nt of f u ncti o nal rea di n g 
i n de pe n de nce (see t he St u d y Pr oce d ure M a n ual or e q ui vale nt). It has o n e t otal i n de x sc ore. 
T he i n de x sc ore is a n or di nal scale wit h hi g h er le v els re pres e nti n g hi g h er f u ncti o nal rea di n g 
i n de pe n de nce. T he F RI I n de x has a s pecifie d recall peri o d of 7 da ys. F or a d diti o nal details 
see t he St u d y Pr o ce d ur e Ma n ual or e q ui val e nt.  
7. 3. 1 0  
N EI V F Q - 2 5 
T he N EI V F Q - 2 5 is a 2 5-ite m, i nter vie wer-a d mi nistere d assess me nt of vis ual f u ncti o ni n g. 
Near a n d dista nce d o m ai ns will als o  be i ncl u de d (t hree a d diti o nal ite ms f or eac h d o mai n). 
It is sc or e d o n a s cale of 0 −1 0 0, wit h hi g her sc ores i n dicati n g better vis ual f u ncti o n. It h as a 
c o m p osite sc ore a n d 1 2 d o mai ns ( ge neral healt h, ge neral visi o n, oc ular pai n, near acti vities, 
dista nce a cti vities, s ocial f u ncti o ni n g, me ntal h ealt h, r ole diffic ulties, de p e n de nc y, dri vi n g, 
c ol or visi o n, a n d peri p heral visi o n). It d o es n ot ha ve a s pecifie d recall peri o d. F or a d diti o nal 
details see t he St u d y Pr o ce d ure M a n ual or e q ui vale nt.  
7. 3. 1 1  
Slit L a m p Bi o micr o sc o p y 
Slit la m p bi o micr osc o p y will be perf or me d as deter mi ne d b y t he Sc h e d ule of St u d y 
Pr oce d ures ( Ta ble  4 a n d Ta ble  5).   

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 5  of 9 6  
Gra di n g scal es base d o n t he N EI/ S U N criteria f or t he assess me nt of A nt eri or C ha m ber Flare 
or Cell ( J a bs 2 0 0 5) a n d Vitre o us Cells a n d Haze (N usse n blatt 1 9 8 5 ) are pr o vi de d i n 
A p pe n di x 1 . 
Slit -la m p e x a m m ust be perf or me d b ef ore t he i nstillati o n of a n y dilati n g or a nest hetic eye 
dr o ps or fl u ores cei n a ge nt. S u bject will re mai n seate d f or t his e x a m. 
7. 3. 1 2  
I ntr a oc ul ar Press ure 
G ol d ma n n t o n o metr y o r T o n o- pe n t o n o meter is re q uire d at r o uti ne st u d y visits f or pre- a n d 
p ost- d ose i ntra oc ular press ure assess me nts.  T he met h o d of I O P meas ure me nt use d f or a 
patie nt m ust re mai n c o nsiste nt t hr o u g h o ut t he st u d y. If pat h ol o gical meas ure me nts are 
o btai ne d wit h T o n o- pe n, c o ntact -t o n o metr y s h o ul d be perf or me d. 
7. 3. 1 2. 1  
P ost I nj ecti o n Assess me nt  
A meas ure m e nt of i ntra o c ular pr ess ure of eit her t h e st u d y e ye  or b ot h e yes ( de pe n di n g o n t he 
visit; refer t o  Ta ble  4 a n d  Ta ble  5) will be o btai ne d a p pr o xi matel y 1 5 mi n utes after a n y I V T 
i njecti o n b y q ualifie d u n mas ke d site staff. If t here are n o safet y c o n cer ns, t he s u bject will be 
per mitte d t o lea ve t he cli nic. T he I O P val ues rec or de d i n m m H g will be e ntere d i nt o t he 
e C R F. If t he I O P p ost- d ose is ≥ 3 0 m m H g, t he s u bject s h o ul d re mai n i n cli nic a n d be 
meas ure d a gai n a p pr o xi matel y 3 0  mi n utes later ( 4 5 – 6 0 mi n utes p ost-i njecti o n). 
Press ure  l o weri n g dr o ps are per mitte d at I n vesti gat or discreti o n. If t here are n o safet y 
c o ncer ns at t hat ti me, a n d t he I O P is <  3 0 m m H g, t he s u bject will be per mitte d t o lea ve t he 
cli nic. T he last p ost-i njecti o n I O P val ue will be rec or de d o n t he a p pr o priat e e C R F.  
I n t he cas e of a n ac ute I O P s pi ke ( ≥ 3 0 m m H g fr o m pre -i njecti o n I O P as m eas ured at 
≥ 6 0 mi n utes p ost-i njecti o n), w hic h ca uses pai n a n d l oss of visi o n, a parace ntesis ma y b e 
perf or me d i n t he a nteri or c ha m ber, t o releas e s o me a q ue o us h u m or a n d reli e ve t he press ure. 
T he fi nal pre-i nter ve nti o n I O P rec or di n g as well as t he p ost-i nter ve nti o n I O P rec or d e d will 
be e nter e d i nt o t he a p plica ble e C R F pa ge. If a p plica ble, a n A d vers e E ve nt e C R F pa ge will be 
c o m plete d.  
7. 3. 1 3  
Dil ate d F u n d us E x a m a n d I n direct O p ht h al m osc o p y  
O p ht hal m osc o p y will be perf or me d as i de ntifie d i n t he Sc he d ule of St u d y Pr oce d ures 
(Ta ble  4 a n d T a ble  5).  
After t he p u pil is dilate d,  t he o ptic ner ve a n d mac ular are e val u ate d at t he slit la m p wit h a 
9 0/ 7 8/ 6 0 di o pter ( or si milar) le ns. T his is f oll o we d b y I n direct O p ht hal m osc o p y (I O) w hic h 
e x a mi nes f or vitre o us haze (t he de gree of i nfla m mati o n) a n d t he peri p h eral reti na, l o o ki n g f or 
reti nal tears after i njecti o n a m o n g ot her t hi n gs. B ot h t he slit la m p a n d I O are d o ne t o get her t o 
e val uate t he p osteri or se g me nt. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 6  of 9 6  
7. 3. 1 4  
Oc ul ar I m a gi n g 
Ce ntral rea di n g ce nter will be use d t o perf or m a n i n de pe n de nt a n al ysis of all i ma ges. 
T he  ce ntr al rea di n g ce nter wi ll pr o vi de sites wit h t he Ce ntral Rea di n g Ce nt er ma n ual a n d 
trai ni n g materials f or s p ecifie d st u d y o c ular i ma ges. Bef ore a n y st u d y i ma ges are o bt ai ne d, 
site pers o n nel, test i ma ges, a n d s yste ms a n d s oft w are ( w here a p plica bl e) will be 
verifie d/ vali date d b y t he rea di n g ce nter as s pecifie d i n t he Ce ntral Rea di n g Ce nter ma n ual. 
All oc ular i ma ges r es ults will be o btai ne d b y trai ne d site pers o n nel at t he st u d y sites a n d 
f or war de d t o t he ce ntral r ea di n g ce nt er f or i n d e pe n de nt a nal ysis a n d/ or st ora ge. N ote: after 
ran d o mizati o n, if a s u bject misses a st u d y visit d uri n g w hic h oc ular i ma ges were s c he d ule d 
t o be ta ke n, t he i ma ges s h o ul d be o btai ne d at t he ne xt sc he d ule d visit (Ta ble  4 a n d Ta ble  5) 
Oc ular i ma ges o bt ai ne d f or t he p ur p ose of t h e st u d y s h o ul d i ncl u de t he f oll o wi n g: 
•  S pectral d o mai n O ptical C o here nce T o m o gra p h y ( S D -O C T)  
•  F u n d us a ut o fl u or esce n ce ( F A F) 
•  C ol or F u n d us P h ot o gra p h y ( C F P)  
•  Fl u orescei n a n gi o gra p h y ( F A)  
A d diti o nal details o n o btai ni n g t hese i ma ges are i ncl u de d i n t he Ce ntral Rea di n g Ce nter 
Ma n ual.  
7. 3. 1 4. 1  
S D -O C T  
S pectral D o mai n O ptical C o here nce T o m o gra p h y ( S D- O C T) will be c ollect e d as deter mi ne d 
b y t he Sc h e d ule of St u d y Pr oce d ures ( Ta ble  4 a n d Ta ble  5). S D-O C T will be perf or me d at 
t he st u d y sites b y trai ne d pers o n nel w h o are certifi e d b y t h e ce ntral rea di n g ce nter. S D-O C T 
i ma gi n g will be perf or me d f or eac h s u bject at t he i nter vals s pecifi e d i n Ta bl e  4 a n d Ta ble  5. 
O nce i ma ges are c ollecte d, t he y will be f or war de d t o t he ce ntral rea di n g ce nter.  
7. 3. 1 4. 2  
F u n d us A ut o fl u oresce nce 
F u n d us A ut o fl u ores ce nce ( F A F) will be perf or me d at t he st u d y sites b y trai ne d pers o n nel 
w h o are certifie d b y t h e ce ntral rea di n g ce nter. F A F i ma gi n g will be perf or me d f or eac h 
s u bject at t he i nter vals s p ecifie d i n Ta ble  4 a n d Ta ble  5. O nce i ma ges are c ollecte d, t he y will 
be f or w ar de d t o t he ce ntr al rea di n g ce nter.  
7. 3. 1 4. 3  
C ol or F u n d us P h ot o gr a p h y ( C F P) 
C ol or F u n d us P h ot o gra p h y ( C F P) will be ta ke n b y trai n e d pers o n n el 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 Ta bl e  4 a n d Ta ble  5. 
O nce i ma ges are c ollecte d, t he y will be f or war de d t o t he ce ntral rea di n g ce nter.  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 7  of 9 6  
7. 3. 1 4. 4  
Fl u ores cei n A n gi o gr a p h y ( F A) 
Fl u orescei n a n gi o gra p h y will be per f or me d at t he st u d y sites b y trai ne d p ers o n nel w h o are 
certifie d b y t he ce ntr al rea di n g ce nter. T he fl u ores cei n a n gi o gra ms ( F As) will be o btai ne d at 
t he i nter vals s pecifi e d i n Ta ble  4 a n d T a ble  5. O nce i ma ges are c ollect e d, t he y will be 
f or war de d t o t he ce ntral r ea di n g ce nt er. 
7. 3. 1 4. 5  
Micr o peri met r y  
Mes o pic micr o p eri metr y of st u d y e ye o nl y will be perf or me d at select st u d y sites  b y trai ne d 
pers o n nel w h o are certifi e d b y t h e ce ntral rea di n g ce nter. Micr o peri metr y will be perf or me d 
o n s u bjects w h o meet eli gi bilit y criteria as d efi ne d i n Secti o n  5 . 
T he micr o peri metr y res ults of t he st u d y e ye will be o btai ne d at pr ot oc ol- s pecifie d visits, as 
s pecifie d i n Ta ble  4 a n d Ta ble  5, a n d will be f or w ar de d t o t he ce ntral rea di n g ce nter f or 
a d diti o nal re vie w. 
7. 3. 1 5  
M a n a ge me nt of C h or oi d al Ne o v asc ul ariz ati o n ( C N V) 
W hile s u bjects wit h acti ve C N V i n t heir st u d y e yes are e x cl u de d fr o m t his st u d y, it is 
p ossi ble t hat C N V de vel o ps d uri n g t he d urati o n of t he st u d y. 
Di a g n osis:  S u bjects s us pecte d of cli nical C N V de vel o p me nt i n t he st u d y e ye m ust ha v e t he 
dia g n osis c o nfir me d wit h S D - O C T a n d F A. C N V c o nfir mati o n b y t he Ce ntral Rea di n g 
Ce nter, usi n g b ot h i ma gi n g m o dalities, is re q uire d pri or t o i nitiati o n of a nti- V E G F treat me nt . 
O n t he st u d y visit w her e C N V is s us pecte d b y t he e val uati n g p h ysi cia n, a n d t he a d diti o nal 
i ma gi n g is ta ke n a n d s u b mitte d f or Ce ntral Rea di n g Ce nter re vie w, it is all o wa ble t o pr ocee d 
wit h t he st u d y d osi n g p er t he assess me nt sc he d ule w hi le a waiti n g Ce ntral R ea di n g Ce nter 
fee d bac k o n C N V dia g n osis. O nce t he dia g n osis is c o nfir me d t he p atie nt ca n be a d mi nistere d 
afli berce pt ( E Y L E A ® ). T his ma y r e q uire a s e parat e visit ( u nsc he d ule d visit). If t here is a 
patie nt safet y c o n cer n pl ease r eac h o ut  t o t he me dical m o nit or t o disc uss ma na ge me nt.  
7. 3. 1 5. 1  
M a n a ge me nt of C h or oi d al Ne o v asc ul ariz ati o n ( C N V)-St u d y E ye   
Tre at me nt ( St u d y E ye) : I n t his pr ot oc ol, o nl y afli berce pt ( E Y L E A® ) is all o we d. 
F oll o w r o uti ne cli nical pr actice i n a d mi nisteri n g afli berce pt per F DA la bel. Treat me nt 
fre q ue n c y wit h a nti- V E G F s h o ul d be base d o n st a n dar d of care re gi me ns t o ma xi mize 
l o n g-ter m vis ual o utc o mes a n d mi ni mize rec urre n ce a n d s u bject b ur de n.  
St u d y Dr u g ( St u d y E ye) : I n s u bj ects w h o de v el o pe d C N V i n t heir st u d y e ye a n d ha v e a 
c o nfir me d dia g n osis fr o m t he Ce ntral Rea di n g ce nter, st u d y dr u g will c o nti n ue b ut it will be 
a d mi nistere d after a nti -V E G F treat me nt, o nce t h e I O P h as ret ur n e d t o a n or mal ra n ge 
( < 3 0 m m H g), a p pr o xi matel y 1 5 – 3 0 mi n utes after t he a nti-V E G F i njecti o n. At t he 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 8  of 9 6  
p h ysicia n’s discreti o n, m a ne u vers s u c h as mil d oc ular di gital massa ge ma y be a p plie d t o t he 
gl o be pri or t o t he i njecti o n t o re d uce t he ris k of c o m plicati o ns sec o n dar y t o i ncreas e d I O P.   
A meas ure m e nt of i ntra o c ular pr ess ure will be o bt ai ne d a p pr o xi matel y 1 5 mi n utes after t he 
sec o n d I V T i njecti o n b y q ualifie d u nmas ke d site staff. If t h ere are n o s afet y c o ncer ns, t h e 
s u bject will be per mitte d t o lea ve t he cli nic. T h e I O P val ues rec or de d i n m m H g will be 
e ntere d i nt o t he e C R F. If t he I O P p ost d ose is ≥ 3 0 m m H g, t he s u bject s h o ul d re mai n i n 
cli nic a n d be meas ure d a gai n a p pr o xi matel y 3 0  mi n utes later  
( 4 5– 6 0 mi n utes p osti njecti o n). Press ure l o weri n g dr o ps are p er mitte d at I n vesti gat or 
discreti o n. If t her e are n o safet y c o n cer ns at t hat ti me, a n d t he I O P is <  3 0 m m H g, t he s u bject 
will be per mitte d t o lea ve t he cli nic. T he last p osti njecti o n I O P val ue will be rec or de d o n t he 
a p pr o priate e C R F.  
I n t he cas e of a n ac ute I O P s pi ke ( ≥ 3 0 m m H g fr o m prei njecti o n I O P as meas ure d at 
≥ 6 0 mi n utes p ost t he sec o n d i njecti o n), w hic h ca uses pai n a n d l oss of visi o n, a parace ntesis 
ma y b e perf or me d i n t he a nteri or c h a m ber, t o release s o me a q u e o us h u m or a n d relie ve t h e 
press ure. T h e fi nal pr ei nter ve nti o n I O P rec or di n g as well as t he p osti nter ve nti o n I O P 
rec or d e d will be e ntere d i nt o t he a p plica ble e C R F pa ge. If a p plica ble, a n A d verse E ve nt 
e C R F pa ge will be c o m plete d.  
St u d y S u bject ( St u d y E ye) : S u bjects recei vi n g C N V treat me nt will c o nti n ue i n t he st u d y 
u ntil e n d of t he st u d y ( W ee k 5 6). If s u bjects o pt t o disc o nti n ue st u d y dr u g, t he y s h o ul d still 
c o nti n ue wit h st u d y visits a n d assess me nts t hr o u g h Wee k 5 6. 
7. 3. 1 5. 2  
M a n a ge me nt of C h or oi d al Ne o v asc ul ariz ati o n ( C N V)-N o n -St u d y E ye    
Tre at me nt ( N o n -St u d y E ye) : I n s u bj ects wit h C N V i n t he n o n-st u d y (fell o w) e ye, f oll o w 
r o uti ne cli nical sta n dar d of care i n dia g n osis a n d treat me nt. If n o n- st u d y e ye treat me nt will 
occ ur o n t he s a me da y as a st u d y d osi n g visit, t he st u d y e ye s h o ul d be d ose d first. T here are 
n o ot her s pecific treat me nt sti p ulati o ns f or n o n-st u d y e ye.  
St u d y Dr u g ( N o n -St u d y E ye) : I n s u bj ects wit h C N V i n t he n o n-st u d y (fell o w) e ye, st u d y 
dr u g will n ot be st o p pe d. 
St u d y S u bject ( N o n -St u d y E ye):  S u bject will c o nti n ue i n t he st u d y u ntil e n d of t he st u d y.  
7. 3. 1 6  
Cli nic al Ge n ot y pi n g S a m ple  
A n o pti o nal o ne- ti me b uccal s wa b will be c ollect e d f or ge n etic mar k er a n al ysis at a n y ti me 
d uri n g t he st u d y p ost-r a n d o mizati o n ( Da y 1 t o E O S). C ollecti o n will o nl y o cc ur if t he s u bject 
has c o nse nte d t o t he o pti o nal pr oce d ure o n t he c o nse nt f or m a n d t here are n o la ws or st u d y 
ce nter p olicies i n place t h at pr o hi bit t he c ollecti o n of sa m ples f or ge netic m ar ker a nal ysis. 
T he ge netic mar ker s a m ple will be use d t o e val uat e t he relati o ns hi ps bet wee n ge netic 
p ol y m or p his ms ass ociate d wit h A M D, baseli ne disease c h aracteristics, a n d res p o nse t o 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 7 9  of 9 6  
a d mi nistrati o n of N G M 6 2 1. If a s u bject d o es n ot wa nt t o partici pate i n t his o pti o nal sa m ple 
c ollecti o n, t his d oes n ot precl u de t heir partici pati o n i n t he trial. 
7. 4  
S af et y a n d Ot her Assess me nts  
7. 4. 1  
A d verse E ve nts  
7. 4. 1. 1  
Defi niti o n of A d verse E ve nts  
A n a d vers e e ve nt ( A E) is defi ne d as a n y u nt o war d me dical occ urre n ce i n a s u bject or cli nical 
i n vesti gati o nal s u bject w h o has bee n a d mi nistere d a p har mace utical pr o d uct t hat d oes n ot 
necessaril y h a ve a ca us al relati o ns hi p wit h t his treat me nt. A treat me nt -e mer ge nt a d verse 
e ve nt ( T E A E) is a n A E t hat is  re p orte d after a d os e of st u d y dr u g. 
A Es are all:  
•  u nfa v ora bl e c ha n ges i n ge neral c o n diti o n. 
•  s u bjecti ve or o bjecti ve si g ns/s y m pt o ms. 
•  c o nc o mita nt diseases or acci de nts.  
•  cli nicall y r ele va nt a d vers e c ha n ges i n la b orat or y p ara meters o bser v e d i n a p artici pa nt i n 
t he c o urse of a cli nical st u d y. 
A Es c o m prise all dist ur b a nces of ge neral healt h st at us, s u bjecti ve a n d o bjecti ve disease 
s y m pt o ms (i ncl u di n g la b orat or y a b n or m alities), a n d acci de nts o bser ve d i n t he c o nte xt of a 
cli nical trial, irres pecti ve of a p ossi ble ca us al relati o ns hi p wit h t he a d mi nistrati o n of t he trial 
s u bsta nce. E ve nts occ urri n g i n t he fra me w or k of a cli nical trial d uri n g dr u g-free, a n d 
p ost-treat me nt peri o ds, or u n der place b o, are als o t o be desi g n ate d as A Es. 
All A Es, w het her v ol u nteere d, elicite d, or n ote d o n p h ysical e x a mi nati o n, will be rec or d e d 
t hr o u g h o ut t he st u d y (i.e., fr o m scree ni n g u ntil e n d of st u d y [ E O S]). 
S u bjects will be q uerie d f or res ol uti o n of o n g oi n g A Es or u ntil a n y u nres ol ve d A Es are 
j u d ge d b y t he PI t o ha v e sta bilize d or if l ost t o f oll o w u p. Res ol uti o n of all A Es will be 
pr o m ptl y d oc u me nte d b y t he cli nic i n t he s u bject’s e C R F. 
A n y pre g na n c y dia g n ose d d uri n g t he st u d y m ust b e re p ort e d i m me diatel y t o t he I n v esti gat or 
a n d S p o ns or, i ncl u di n g pre g na nc y i n fe male p art n ers of male s u bjects. T he pre g na nc y will be 
f oll o we d t o ter m a n d/ or o utc o me a n d t his o utc o me m ust be re p orte d t o t he S p o ns or. 
Pre g n a nc y, i n a n d of itself, is n ot re gar d e d as a n A E or seri o us a d v erse e ve nt ( S A E) u nless 
t he birt h res ults i n a c o n ge nital a n o mal y/ birt h d efect or t here is s us pici o n t h at t he st u d y 
treat me nt ma y ha v e i nterfere d wit h t he effecti ve n ess of a c o ntrace pti ve me dicati o n or 
met h o d. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 0  of 9 6  
T he PI will rate t he se v erit y of s yste mic A Es a n d oc ular A Es usi n g differe nt scales. T he PI 
will rate t he se verit y of s yst e mic A Es usi n g t he C T C A E v 5 t o gra de t he se verit y. E ac h  
C T C A E v 5 ter m is a Me dical Dicti o nar y f or Re g ulat or y A cti vities ( Me d D R A) L o west Le v el 
Ter m ( L L T). T he C T C A E dis pla ys Gra des 1 – 5 wit h u ni q ue cli nical descri pti o ns of se verit y 
f or eac h A E. N ot all Gra des are a p pr o pri ate f or all A Es. T heref ore, s o me A Es are liste d wit h 
fe wer t ha n fi ve o pti o ns f or Gra d e selecti o n. Gra d e 5 ( Deat h) is n ot a p pr o priate f or s o me A Es 
a n d, t heref ore, is n ot a n o pti o n. 
T he PI will rate t he se v erit y of oc ular A Es usi n g t he defi niti o ns bel o w. F or eac h e pis o de, t he 
hi g hest se v erit y gra d e att ai ne d s h o ul d be re p orte d. 
MI L D = D oes n ot i nterfere wit h s u bject’s us ual f u ncti o n (a ware ness of s y m pt o ms or si g ns, 
b ut easil y t oler ate d [ acce pta ble]).  
M O D E R A T E = I nterf er es t o s o me e xte nt wit h s u bj ect’s us ual f u ncti o n (e n o u g h disc o mf ort 
t o i nterfere wit h us ual acti vit y [ dist ur bi n g]). 
S E V E R E = I nterfer es si g nifica ntl y wit h s u bject’s us ual f u ncti o n (i nca p acit y t o w or k or t o d o 
us ual acti vities [ u nacce pt a ble])  
7. 4. 1. 2  
Defi niti o n of Seri o us A d verse E ve nts a n d S A E Re p orti n g  
A n S A E is a n y u nt o w ar d me dical occ urre n ce at a n y d ose t h at res ults i n a n y of t he f oll o wi n g 
o utc o mes: 
•  Deat h  
•  A life -t hreate ni n g e ve nt (i.e., p uts t he s u bject, i n t he vie w of t he PI, at i m me diate ris k of 
deat h)  
•  I n p atie nt h os pitalizati o n or pr ol o n gati o n of e xisti n g h os pitalizati o n 
•  A persiste nt or si g nifica nt disa bilit y/i nca p acit y  
•  A c o n ge nital a n o mal y/ birt h defect  
•  I m p ort a nt me dical e v e nt t hat ma y re q uire m e dical or s ur gical i nter v e nti o n t o pre ve nt o ne 
of t he a b o ve o utc o m es 
A n u ne x pecte d a d verse dr u g e ve nt is a n y a d v erse dr u g e ve nt t he s pecificit y or se verit y of 
w hic h is n ot c o nsiste nt wit h t he c urre nt I B or, if a n I B is n ot re q uire d or a v aila ble, t he ge neral 
i n vesti gati o nal pla n or else w her e i n t he c urre nt a p plicati o n. 
A n A E is ass ociate d  wit h t he use of t he dr u g if a reas o na ble p ossi bilit y e xists t hat t he e ve nt 
ma y h a ve bee n ca use d b y t he dr u g. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 1  of 9 6  
S A Es t hat are u ne x pecte d a n d relate d t o N G M 6 2 1 are re p orta ble t o Re g ul at or y A ut h orities. 
All S A Es will be re p orte d b y t he PI t o t he S p o ns or a n d will be re p orte d t o t he res p o nsi ble 
Et hics C o m mittee ( E C) i n acc or d a nce wit h l ocal re q uire me nts.  
T he S p o ns or’s assi g ne d Safet y R e pres e ntati ve will be n otifie d i n writi n g (e. g., e mail or 
facsi mile) wit hi n 2 4 h o urs of w he n a n S A E is first rec o g nize d or re p orted. T he Safet y 
Re prese ntati ve will s u bse q ue ntl y n otif y t he S p o ns or a n d t he S p o ns or’s assi g ne d M e dical 
M o nit or or desi g n ee of all re p orte d S A Es. 
7. 4. 1. 3  
Cl assific ati o n of Se verit y of A d verse E ve nt  
T he se verit y of A Es will be cate g orize d as s h o w n bel o w. 
C ate g oriz ati o n of Se verit y of A d verse E ve nts   
Mil d  
T he e ve nt is mi n or a n d d oes n ot ca use si g nifica nt disc o mf ort t o s u bject or 
c ha n ge i n acti vities of dail y li vi n g ( A D L); partici pa nt is a ware of 
s y m pt o ms, b ut s y m pt o ms are easil y t olerate d. 
M o der ate  
T he e ve nt is a n i nc o n v e nie nce or c o ncer n t o t he s u bject a n d ca uses 
i nterfer e nce wit h A D L, b ut t he partici pa nt is a ble t o c o nti n ue wit h A D L. 
Se vere  
T he e ve nt si g nifica ntl y i nterferes wit h A D L a n d t he s u bject is i nca pacitate d 
a n d/ or u na ble t o c o nti n ue wit h A D L.  
P ot e nti all y 
lif e 
t hre ate ni n g  
A n e ve nt/reacti o n i n w hic h t he s u bject was at ris k of deat h at t he ti me of t h e 
e ve nt/reacti o n; it d oes n ot refer t o a n e ve nt/reacti o n w hic h h y p ot h eticall y 
mi g ht ha ve ca use d d eat h if it were m ore s e vere.  
7. 4. 1. 4  
Assess me nt of C a us alit y of A d ver se E ve nts  
T he mas ke d, e v al uati n g i n vesti gat ors s h o ul d use t heir k n o wle d ge of t he s u bject, t he 
circ u msta nces s urr o u n di n g t he e ve nt, a n d a n e val uati o n of a n y p ote ntial alter nati ve ca uses t o 
deter mi ne w het h er a n A E is c o nsi dere d t o be relate d t o t he st u d y dr u g, i n dicati n g “ yes” or 
“ n o” acc or di n gl y. T he f oll o wi n g g ui da nce s h o ul d be ta ke n i nt o c o nsi derati o n (see Ta bl e  7): 
•  Te m p oral rel ati o ns hi p of e ve nt o nset t o t he i nitiati o n of st u d y dr u g 
•  C o urse of t he e v e nt, c o nsi deri n g es peci all y t he effects of d ose re d ucti o n, 
disc o nti n uati o n of st u d y dr u g, or rei ntr o d u cti o n of st u d y dr u g (as a p plica bl e) 
•  K n o w n ass ociati o n of t he e ve nt wit h t he st u d y dr u g or wit h si milar treat me nts  
•  K n o w n ass ociati o n of t he e ve nt wit h t he disease u n der st u d y 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 2  of 9 6  
•  Prese nce of ris k fact ors i n t he s u bject or use of c o nc o mita nt me dicati o ns k n o w n t o 
i ncreas e t he occ urr e nce of t he e ve nt 
•  Prese nce of n o n -tr eat me nt-relate d fact ors t hat are k n o w n t o be ass ociate d wit h t he 
occ urr e nce of t he e v e nt  
T a ble 7. 
C a us al Attri b uti o n G ui d a nce  
Is t he a d vers e e v e nt s us pecte d t o be ca use d b y t he st u d y dr u g o n t he b asis of facts, e vi d e nce, 
scie nce-base d rati o nales, a n d cli nical j u d g me nt?  
Y E S  
T here is a pl a usi ble te m p or al rel ati o ns hi p bet wee n t he o nset of t he a dverse eve nt a n d 
a d mi nistr ati o n of t he st u dy dr u g, a n d t he a dvers e eve nt c a n n ot b e re a dily ex pl ai ne d by t he 
s u bject's cli nic al st ate, i nterc urre nt ill ness, or c o nc o mit a nt t her a pies; a n d/ or t he a dverse 
eve nt f oll o ws a k n o w n p atter n of res p o nse t o t he st u dy dr u g; a n d/ or t he a dverse eve nt a b ates 
or res olves u p o n disc o nti n u ati o n of t he st u dy dr u g a n d, if a p plic a ble, re a p pe ars u p o n 
re-c h alle n ge. 
 
N O  
A n a dverse eve nt will be c o nsi dere d rel ate d,  u nless it f ulfills t he criteri a s pecifie d bel o w.  
Evi de nce exists t h at t he a dverse eve nt h as a n eti ol o gy ot her t h a n t he st u dy dr u g (e. g., 
preexisti n g me dic al c o n diti o n, u n derlyi n g dise ase, i nterc urre nt ill ness, or c o nc o mit a nt 
me dic ati o n); a n d/ or t he a dvers e eve nt h as n o pl a usi ble te m p or al rel ati o ns hi p t o 
a d mi nistr ati o n of t he st u dy dr u g (e. g., c a n cer di a g n ose d 2 d ays after first d ose of st u dy 
dr u g).  
 
7. 4. 1. 5  
Pr oce d ures f or R ec or di n g A d verse E ve nts  
I n v esti gat ors s h o ul d use c orrect me dical ter mi n ol o g y/c o n ce pts w he n rec or di n g A Es o n t he 
A d verse E v e nt e C R F. A v oi d c oll o q uialis ms a n d a b bre viati o ns. O nl y o n e A E ter m s h o ul d be 
rec or d e d i n t he e v e nt fiel d o n t he A d verse E ve nt e C R F. F or t he p ur p os es of re p orti n g e ve nts 
of i nfecti o n a n d i nfla m m ati o n, t he f oll o wi n g ter ms a n d defi niti o ns s h o ul d be use d: 
•  Iritis: t he pr ese nce of i nfl a m mat or y cells i n t he a nt eri or c h a m ber. N ote: T h e prese nce 
of a q ue o us flare al o ne will n ot c o nstit ute iritis b ut s h o ul d be d oc u me nte d as a n 
a nteri or c h a m ber flare f or A E re p orti n g p ur p oses.  
•  Iri d o c yclitis: t he prese n ce of i nfla m mat or y cells i n b ot h t he a q ue o us a n d vitre o us 
•  Vitritis: t he prese nce of acti ve i nfla m mati o n i n t he vitre o us, de m o nstrate d b y t he 
prese nce of i nfla m mat or y cells (tr ace or greater)  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 3  of 9 6  
•  Acti ve i nfla m mati o n i n t he vitre o us s h o ul d be cli nicall y differe ntiate d fr o m cell ular 
de bris fr o m pri or e pis o des of i nfla m mati o n, he m orr ha ge, or ot h er ca uses. 
•  E n d o p ht hal mitis: diff use i ntra oc ular i nfla m mati o n pre d o mi na ntl y i n v ol vi n g t he 
vitre o us ca vit y b ut als o i n v ol vi n g t he a nteri or c h a m ber, i m pl yi n g a s us pecte d 
u n derl yi n g i nf ecti o us ca use. A c ult ure is re q uire d pri or t o i nitiati n g a nti bi otic 
treat me nt f or pres u me d e n d o p ht hal mitis. Res ults of bacterial or f u n gal c ult ures, 
treat me nt gi ve n, an d fi nal o p ht hal m ol o gic o utc o me s h o ul d als o be pr o vi de d i n t he 
details secti o n of t he e v e nt e C R F.  
N ote: Trace be ni g n, a q u e o us pi g me nte d cells visi ble o n slit- la m p e x a mi nati o n t hat are ca use d 
b y dilati o n a n d are n ot R B Cs or W B Cs or t he res ult of a n y o c ular dis or d er s h o ul d n ot be 
rec or d e d as a n A E. 
7. 4. 1. 6  
Di a g n osis vers us Si g ns a n d S y m pt o ms  
A dia g n osis (if k n o w n) s h o ul d be rec or de d o n t he A d verse E v e nt e C R F rat her t ha n i n di vi d ual 
si g ns a n d s y m pt o ms (e. g., rec or d o nl y li ver fail ure or he patitis rat her t h a n ja u n dice, asteri xis, 
a n d ele vat e d tra nsa mi nas es). H o we v er, if a c o nstellati o n of si g ns a n d/ or s y m pt o ms ca n n ot be 
me dicall y c har acterize d as a si n gle dia g n osis or s y n dr o me at t he ti me of re p orti n g, eac h 
i n di vi d ual e ve nt s h o ul d be rec or de d o n t he A d vers e E ve nt e C R F. If a dia g n osis is 
s u bse q ue ntl y esta blis he d, all pre vi o usl y re p orte d A Es base d o n si g ns a n d s y m pt o ms s h o ul d 
be n ullifie d a n d re pl ace d b y o ne A E re p ort base d o n t he si n gle dia g n osis, wit h a starti n g d ate 
t hat c orres p o n ds t o t he st arti n g d ate of t he first s y m pt o m of t he e ve nt ual dia g n osis. 
7. 4. 1. 7  
A d verse E ve nts T h at A re Sec o n d ar y t o Ot her E ve nts  
I n ge ner al, A Es occ urri n g sec o n dar y t o ot her e ve nts (e. g., casca de e ve nts or cli nical 
se q uelae) s h o ul d be i de ntifie d b y t heir pri mar y ca use, wit h t he e x ce pti o n of se vere or seri o us 
sec o n dar y e ve nts. H o w e ver, me dicall y si g nifica nt A Es occ urri n g s ec o n d ar y t o a n i nitiati n g 
e ve nt t hat ar e se parate d i n ti me s h o ul d be rec or d e d as i n de pe n de nt e v e nts o n t he A d verse 
E ve nt e C R F. F or e x a m ple:  
•  If v o miti n g res ults i n mil d de h y drati o n wit h n o a d diti o nal treat me nt i n a healt h y a d ult, 
o nl y v o miti n g s h o ul d be re p orte d o n t he e C R F. 
•  If v o miti n g res ults i n se v ere de h y drati o n, b ot h e ve nts s h o ul d be re p orte d se paratel y 
o n t he e C R F. 
•  If a se v ere gastr oi ntesti nal he m orr ha ge lea ds t o re nal fail ure, b ot h e v e nts s h o ul d be 
re p orte d se p ar atel y o n t he e C R F. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 4  of 9 6  
•  If dizzi ness lea ds t o a fall a n d c o nse q ue nt fract ure, all t hree e v e nts s h o ul d be re p ort e d 
se parat el y o n t h e e C R F. 
•  If ne utr o pe ni a is acc o m pa nie d b y a n i nfecti o n, b ot h e ve nts s h o ul d be re p orte d 
se parat el y o n t h e e C R F. 
All A Es s h o ul d be rec or d e d se par atel y o n t he A d v erse E ve nt e C R F if it is u nclear as t o 
w het her t he e ve nts ar e ass ociate d . 
7. 4. 1. 8  
Si g ht T hre ate ni n g E ve nt  
F or t his st u d y me dicall y i m p orta nt e ve nts c o m pris e t he f oll o wi n g si g ht t hreate ni n g e ve nts, 
w hic h are c o nsi der e d t o be of s peci al i nterest a n d b y defa ult are t o be re p orte d as S A Es:  
•  A d verse E v e nts t hat ca us e d a decrease i n vis ual ac uit y of >  3 0 E T D R S letters or 
> + 0. 6 L o g M A R lasti n g >  1 h o ur, c o m pare d wit h t he last assess me nt of vis ual ac uit y at 
t he last visit or fr o m baseli ne B C V A o n St u d y D a y 1.  
•  A d verse E v e nts t hat ca us e a decrease i n vis ual ac uit y t o t he le vel of Li g ht Perce pti o n or 
w orse lasti n g > 1 h o ur.  
•  A d verse E v e nts t hat re q uire s ur gical i nter v e nti o n (e. g., c o n ve nti o nal s ur ger y, vitre o us ta p 
o r bi o ps y wit h i ntra vitreal i njecti o n of a nti-i nfecti ves, or laser or reti nal cr y o pe x y wit h 
gas) t o pre ve nt p er ma n e nt l oss of si g ht.  
•  A d verse E v e nts ass ociate d wit h se vere i ntra o c ular i nfla m mati o n (i.e., e n d o p ht hal mitis, 
4 + a nteri or c ha m ber cell/flare or 4 +  vitritis).  
•  A d verse E v e nts t hat, i n t he o pi ni o n of t he I n vesti gat or, m a y re q uire me dical i nter ve nti o n 
t o pre ve nt per m a ne nt l oss of si g ht.  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 5  of 9 6  
8  St atistic al C o nsi der ati o ns  
A detaile d statistical a nal ysis pla n ( S A P) will be pr o vi de d a n d fi nalize d pri or t o t he s t u d y 
data base l oc k or u n mas ki n g. N o discre pa n cies are e x pecte d bet wee n t he S A P a n d t he 
pr ot oc ol. H o we v er, if t here ar e discre pa nci es bet w ee n t his secti o n of t he pr ot oc ol a n d t he 
fi nal S A P, t he S A P will o verri de t he pr ot oc ol. 
I n ge ner al, descri pti ve statistics i ncl u di n g t he n u m ber of n o n- missi n g o bs er vati o ns ( n), 
arit h metic mea n ( mea n), sta n dar d de viati o n ( S D), me dia n, mi ni m u m ( mi n), a n d ma xi m u m 
( ma x) will be prese nte d b y treat me nt gr o u p f or c o nti n u o us e n d p oi nts. Fre q u e nc y a n d 
perce nt a ge distri b uti o n will be prese nte d b y treat me nt gr o u p f or cate g ori cal e n d p oi nts.  
8. 1  
A n al ysis Sets 
S u bjects will be a nal yze d usi n g t he f oll o wi n g a n al ysis sets:  
•  M o difie d I nte nt -T o -Treat ( mI T T) A nal ysis Set: All ra n d o mize d a n d treate d ( wit h at least 
o ne d ose of st u d y dr u g) s u bjects.  T his a nal ysis set will be use d f or all efficac y a n al ys es 
a n d s u bjects will be a nal yz e d base d o n t he treat me nt gr o u p i nt o w hic h t he y are 
ra n d o mize d. 
•  Per Pr ot oc ol ( P P) A nal ysis Set: a s u bset of s u bjects i n t he mI T T A n al ysis S et w h o ha ve 
n o pr ot oc ol de viati o ns t hat aff ect t he G A l esi o n assess me nts ( b y F A F).  T his a nal ysis set 
will be use d f or se nsiti vit y a n al ys es t o s u p p ort t he mI T T a nal yses. 
•  Safet y A nal ysis Set: All  treate d s u bjects. T his a nal ysis set will be use d f or all safet y 
a nal ys es a n d s u bjects will be a nal yz e d base d o n t h e act ual treat me nt t he y recei ve.   
•  P har mac o ki netic ( P K) A nal ysis Set: a s u bset of s u bjects i n t he Safet y A nal ysis Set w h o 
ha ve q ua ntifia ble P K meas ure me nts  p ost first d os e. T his a nal ysis set  will be use d f or all 
P K a nal ys es a n d s u bjects will be a nal yze d b ase d o n t he act ual treat me nt t he y recei v e.  
8. 2  
De m o gr a p hics a n d Ot her B aseli ne C h ar acteristics  
De m o gra p hics (e. g., a ge, se x, race, etc.) a n d ot her baseli ne c haracteristics ( b o d y w ei g ht, iris 
c olor , etc.) will be s u m marize d wit h descri pti ve st atistics b y treat me nt gr o u p f or eac h 
a nal ysis s et.  
8. 3  
Effic ac y A n al yses 
All efficac y a n al ys es will be perf or me d bas e d o n d ata c ollecte d f or st u d y e ye w he ne v er 
a p plica ble.  All efficac y a nal yses will be perf or me d usi n g t he mI T T A n al ysis Set. T he P P 
A nal ysis Set will b e use d f or se nsiti vit y a n al ys es t o s u p p ort t he pri mar y a n d sec o n dar y 
efficac y a n al ys es (t he mI T T a nal yses).  

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 6  of 9 6  
8. 3. 1  
Pri m ar y Effic ac y A n al yses 
8. 3. 1. 1  
Pri m ar y Esti m a n d 
T he esti ma n d  f or t he pri mar y i nterest of t his st u d y is defi n e d as f oll o ws: 
1.  Treat me nt: N G M 6 2 1 Q 4 W, N G M 6 2 1 Q 8 W, a n d p o ole d S ha m ( S ha m i njecti o ns Q 4 W 
or Q 8 W ). 
2.  P o p ulati o n: s u bjects wit h ge o gra p hic atr o p h y sec o n dar y t o a ge -relat e d mac ular 
de ge ner ati o n as defi n e d b y t he i ncl usi o n- e x cl usi o n criteria of t h e st u d y.  
3.  E n d p oi nt: rate of c ha n ge i n G A lesi o n area as meas ure d b y F A F o ver t he 5 2 wee ks of 
treat me nt. 
4.  I nter-c urre nt e ve nts a n d t heir c orres p o n di n g strate gies:  
I nterc urre nt E ve nts 
Esti m a n d Str ate gies  
treat me nt or st u d y d isc o nti n uati o n 
H y p ot hetical “as o w n treat me nt gr o u p ” 
strate g y: Cli nical c o urse is t he sa me as ot her 
s u bjects i n t he sa me treat me nt gr o u p, w h o 
ha d n ot disc o nti n ue d st u d y treat me nt. 
treat me nt no n -c o m plia nce 
Treat me nt P olic y strate g y: All o bser v e d 
val ues of t he varia ble are use d, re gar dless of 
w het her or n ot t he s u bject ha d e x perie nce d 
t he i nterc urre nt e ve nt. 
d ose i nterr u pti o n  
Treat me nt P olic y strate g y  
initiati o n or a dj ust me nt of 
c o nc o mita nt me dicati o n  
Treat me nt P olic y strate g y  
an y ot h er maj or pr ot o c ol de viati o ns  
Treat me nt P olic y strate g y  
i nter me diate e v e nts lea di n g t o 
i nter me diate missi n g f or t he F A F 
assess me nts  
H y p ot hetical “as o w n treat me nt gr o u p ” 
strate g y 
 
5.  P o p ulati o n- le vel s u m mar y: t he treat me nt gr o u p differe n ce b et wee n eac h N G M 6 2 1 
gr o u p a n d t he p o ole d S ha m gr o u p i n t he mea n c ha n ge fr o m baseli ne t o Wee k 5 2 i n 
G A lesi o n area as meas ur e d b y F A F.  
8. 3. 1. 2  
M ai n Esti m ati o n 
T he G A lesi o n area (at b aseli ne, Wee k 2 4 , a n d W ee k 5 2) will be a n al yze d usi n g a ra n d o m 
c oeffi ci e nts m o del. T he m o del i ncl u des ter ms f or ti me (c o nti n u o us varia ble ass u mi n g 
li nearit y) a n d treat me nt-b y -ti me i nteracti o n. T he i nterce pt a n d sl o p e of ti me are ass u me d t o 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 7  of 9 6  
be ra n d o m effects wit h a bi variate n or mal distri b uti o n a n d a n u nstr uct ure d ( U N) c o v aria nce 
matri x w hile t he treat me nt -b y -ti me i nteracti o n is ass u me d t o be a fi x e d effect.  
 
 
 
Wit hi n t he fra me w or k 
of t his m o del, a p oi nt esti mate of t he treat me nt gr o u p differe n ce i n t he re gressi o n sl o pe 
bet wee n eac h N G M 6 2 1 gr o u p a n d t he p o ole d S ha m gr o u p will be pr o vi d e d. 
T he  c orr es p o n di n g t w o-si de d 9 5 % c o nfi de n ce i nter val a n d p-v al ue f or t h e p oi nt esti mate will 
als o be prese nt e d.  
A hierar c hical testi n g pr o ce d ure will be use d t o c o ntr ol t he fa mil y -wise t y p e -I err or rate 
ass ociate d wit h t he tests of t he t w o N G M 6 2 1 gr o u ps ( N G M 6 2 1 Q 4 W vs p o ole d S ha m a n d 
N G M 6 2 1 Q 8 W vs p o ole d S ha m). S pecificall y, t h e c o m paris o n bet w ee n N G M 6 2 1 Q 4 W a n d 
p o ole d S ha m will be perf or me d first. If t his test is statisticall y si g nifica nt at t he 5 % le v el, 
t he n t he c o m paris o n bet wee n N G M 6 2 1 Q 8 W a n d p o ole d S ha m will be perf or me d. If t he first 
test is n ot statisticall y si g nifica nt at t he 5 % le v el, t he n t he c o m paris o n b et w ee n N G M 6 2 1 
Q 8 W a n d p o ole d S ha m will be c o nsi dere d e x pl orat or y. 
8. 3. 1. 3  
Se nsiti vit y A n al yses 
Se nsiti vit y a n al ys es will be perf or me d t o assess t h e r o b ust ness of t he mai n esti mat or of t he 
pri mar y esti ma n d. T hese se nsiti vit y a nal yses will be perf or me d wit h missi n g dat a i m p ute d b y 
t he m ulti ple i m p utati o n a p pr oac h usi n g t he Mar k o v C hai n M o nte Carl o ( M C M C) met h o d, a 
place b o - b ase d patter n mi xt ure m o del, a n d a ti p pi n g p oi nt met h o d, res p ecti v el y. T h e details of 
t hese a nal yses will be pr o vi de d i n t he S A P.  
 
 
 
T he wit hi n -s u bject err ors are ass u me d t o be i n de pe n de nt a n d i de nticall y 
distri b ute d n or mal ra n d o m varia bles, a n d are ass u me d t o be i n de pe n de nt of t he ra n d o m 
i nterce pt. T he d etails of t his a nal ysis will be pr o vi de d i n t he S A P. 
8. 3. 2  
Sec o n d ar y Effic ac y A n al yse s  
Sec o n dar y efficac y e n d p oi nts i ncl u de c ha n ge fr o m baseli ne at Wee k 5 2 i n G A lesi o n area, 
t he s q uare r o ot of G A lesi o n area, B C V A sc ore, L L V A letter sc ore, L L D i n E D T R S letters at 
a starti n g dista n ce of 4 m eters, bi n oc ular rea di n g s pee d ( b y M N Rea d or Ra d ner rea di n g 
c harts), bi n oc ular critical pri nt size ( b y M N Rea d or Ra d ner rea di n g c h arts), F RI c o m p osite 
sc ore, a n d N EI V F Q-2 5, as well as c h a n ge a n d p erce nt c ha n ge of C H 5 0 fr o m baseli ne at eac h 
visit.  
C CI
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 8  of 9 6 
T he c ha n ge fr o m bas eli ne will be a nal yz e d usi n g a li near mi x e d -effects m o del. T he m o del 
i ncl u des fi x e d effects f or treatme nt, visit, treat me nt -b y -visit i nteracti o n, a n d t he baseli ne 
o utc o me val ue as a c o variate. T he c o v aria nce str u ct ure f or t his m o del will be ass u me d t o be 
u nstr uct ure d. If t he m o del d oes n ot c o n ver ge u n d er t his ass u m pti o n, t he n a c o m p o u n d 
s y m metr y c o v aria n ce str uct ure will be use d. Wit hi n t he fra me w or k of t his m o del, a p oi nt 
esti mate of t he treat me nt gr o u p differe nce at Wee k 5 2 bet wee n eac h N G M 6 2 1 gr o u p a n d t he 
p o ole d S ha m gr o u p will be pr o vi de d. T he c orres p o n di n g t w o-si de d 9 5 % c o nfi de nce i nter val 
a n d p-val u e f or t he p oi nt esti mate will als o be pres e nte d.  
8. 4  
S af et y A n al yses 
A d verse e ve nts will be c o de d usi n g t he M e dical Dicti o nar y f or Dr u g Re g ulat or y A cti vities 
( Me d D R A). O c ular a n d s yste mic treat me nt e mer ge nt a d vers e e ve nts ( T E A Es) will be 
s u m marize d b y pri mar y s yste m or ga n class a n d preferre d ter m. Act ual val u es a n d c ha n ge 
fr o m baseli ne val u es f or vital si g ns, cli nical la b orat or y ( he mat ol o g y a n d c he mistr y) tests a n d 
ot her c o nti n u o us varia bles ( b ot h oc ular a n d n o n- oc ular) will be s u m marize d wit h descri pti ve 
statistics. C o nc o mita nt me dicati o ns, p h ysi cal e x a mi nati o ns, a n d ot her cate g orical (safet y) 
varia bles ( b ot h oc ul ar a n d n o n- oc ular) will be s u m marize d wit h fre q ue nc y a n d p erce nta ge 
distri b uti o n. All safet y a n al yses will be perf or me d usi n g t he Safet y A nal ysis Set.  
8. 5  
P h ar m a c o ki netics A n al yses  
I n di vi d ual a n d m ea n ser u m N G M 6 2 1 c o nce ntrati o n –ti me data will be ta b ulate d a n d pl otte d 
b y c o h ort/ d ose le vel. 
 
 
A d diti o nal P K a nal yses a n d/ or s u m mar y statistics will be c o n d ucte d as a p pr o priate. All P K 
a nal ys es will be perf or m e d usi n g t he P K A n al ysis Set.  
8. 6  
S a m ple Size D eter mi n ati o n  
S u bjects will be ra n d o mize d i n a 2: 1: 2: 1 rati o t o recei ve treat me nt wit h N G M 6 2 1 Q 4 W, 
S ha m Q 4 W, N G M 6 2 1 Q 8 W, or S ha m Q 8 W. S u bjects fr o m t he t w o S ha m gr o u ps will be 
p o ole d i n t he data a n al ysis. 
A sa m ple size of 1 0 6 s u bjects per treat me nt gr o u p (i.e., 3 1 8 s u bjects i n t otal) is e x pecte d t o 
pr o vi de a p pr o xi matel y 9 0 % ( N G M 6 2 1 Q 4 W vs p o ole d S ha m) a n d 8 5 % ( N G M 6 2 1 Q 8 W vs 
p o ole d S ha m) p o wer t o d etect a statisticall y si g nifi ca nt treat me nt gr o u p differe nce i n t he rate 
of c ha n ge i n G A lesi o n area o ver t he 5 2 w ee ks of treat me nt. T he p o w er is esti mate d base d o n 
si m ulati o ns ass u mi n g a mea n G A lesi o n area of 8 m m2 at baseli ne f or all s u bjects, a c o m m o n 
sta n dar d de viati o n of 4 m m 2 f or G A lesi o n area, a li near sl o pe of 2 m m 2 per year f or t he 
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 8 9  of 9 6  
p o ole d S ha m gr o u p, 1. 4 m m 2 per year f or N G M 6 2 1 Q 4 W a n d 1. 4 5 m m2 per year f or N G M 
6 2 1 Q 8 W, a wit hi n -s u bject c orr elati o n of 0. 9 5, a statistical si g nifica n ce le v el of 5 % (t w o-
si de d), a n d a 1 0 % of s u bj ect dr o p o ut rat e. T hese ass u m pti o ns are base d o n p u blis he d data 
 
 
 
  
 
 
 
C CI
C CI

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 9 0  of 9 6  
9  S u p p orti n g D oc u me nt ati o n a n d O per ati o n al C o nsi der ati o ns  
9. 1  
Re g ul at or y, Et hic al, a n d St u d y O versi g ht C o nsi der ati o ns  
9. 1. 1  
I nf or me d C o nse nt Pr ocess  
T his st u d y will be c o n d u cte d i n c o m plia nce wit h I nter nati o nal C o nfere nce o n Har m o nisati o n 
(I C H) E 6 G o o d Cli nical Practice: C o ns oli date d G ui da nce pertai ni n g t o i nf or me d c o nse nt. 
At  t he first visit, pri or t o i nitiati o n of a n y st u d y-relate d pr oce d ures, s u bjects m ust gi ve t heir 
writte n c o nse nt t o partici pate i n t he st u d y after h a vi n g bee n i nf or me d a b o ut t he nat ure a n d 
p ur p ose of t he st u d y, partici pati o n/ter mi nati o n c o n diti o ns, a n d ris ks a n d be nefits. 
T he  i nf or me d c o ns e nt d o c u me nt m ust be si g ne d a n d date d b y t he s u bject pri or t o st u d y 
part ici pati o n. A c o p y of t he i nf or me d c o ns e nt d oc u me nt m ust be pr o vi de d t o t he s u bject. 
Si g ne d c o ns e nt f or ms m ust re mai n i n t he s u bject’s st u d y file a n d b e a v aila ble f or verificati o n 
b y S p o ns or or its re prese ntati ve at a n y ti me.  
9. 1. 2  
Et hics C o m mittee  
T his pr ot oc ol, t he i nf or me d c o nse nt d oc u me nt, a n d all rele va nt s u p p orti n g data m ust be 
s u b mitte d t o t he I R B/ E C f or a p pr o v al. I R B/ E C a p pr o val of t he pr ot oc ol, i nf or me d c o nse nt 
d oc u me nt, a n d a n y a d vertise me nt use d t o recr uit st u d y s u bjects m ust be o bt ai ne d bef ore t he 
st u dy ma y be i nitiate d.  
T he PI is r es p o nsi ble f or kee pi n g t he I R B/ E C a d vise d of t he pr o gress of t he st u d y a n d of a n y 
c ha n ges ma d e t o t he pr ot oc ol as dee me d a p pr o pri ate, b ut i n a n y cas e, at least o nce a year. 
T he PI is als o res p o nsi ble f or n otif yi n g t he I R B/ E C of a n y re p ort a ble a d v erse e ve nts ( A Es) 
t hat occ ur d uri n g t he st u d y. 
9. 1. 3  
Pr ot oc ol A d here nce  
T he I n vesti gat or m ust a d here t o t he pr ot o c ol as detaile d i n t his d oc u me nt a n d a gree t h at t he 
S p o ns or m ust a p pr o ve a n y c h a n ges t o t he pr ot o c ol pri or t o see ki n g a p pr o v al fr o m t he 
I R B/ E C. T here will be n o alterati o ns i n t he pr ot oc ol wit h o ut a gree me nt bet wee n t he S p o ns or 
a n d t he I n vesti gat or. T h ere will be n o alterati o ns i n t he pr ot oc ol affecti n g s u bject safet y 
wit h o ut t he e x press writte n a p pr o val of t he S p o ns or, I n vesti gat or, a n d t h e I R B/ E C. 
9. 1. 4  
C o nfi de nti alit y a n d Pri v ac y  
All i nf or mati o n pr o vi de d re gar di n g t he st u d y, as well as all i nf or mati o n 
c ollecte d/ d oc u me nte d d uri n g t he c o urse of t he st u d y, will be re gar d e d as c o nfi de ntial. 
T he  I n vesti gat or a grees n ot t o discl ose s uc h i nf or mati o n i n a n y w a y wit h o ut pri or writte n 
per missi o n fr o m t he S p o ns or. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 9 1  of 9 6  
A n y p u blicati o n of t he res ults, eit her i n part or i n t otal (articles i n j o ur nals or ne ws pa p ers, 
oral prese nt ati o ns, a bstracts, etc.) b y t he I n v esti gat or or t heir re prese nt ati ve(s), s hall re q uire 
pri or n otificati o n a n d r e vie w, wit hi n a reas o n a ble ti me fra me, b y t he S p o ns or, a n d ca n n ot b e 
ma de i n vi olati o n of t he S p o ns or’s c o nfi de ntialit y restricti o ns or t o t he detri me nt of t he 
S p o ns or’s i ntellect ual pr o pert y ri g hts. 
9. 1. 5  
Cli nic al M o nit ori n g  
T he  S p o ns or or desi g nee (e. g., Cli nical Researc h Ass ociate ( C R A)) will be res p o nsi ble f or 
m o nit ori n g t his cli nical trial. T he C R A will m o nit or t he st u d y c o n d uct, pr o per e C R F a n d 
s o urce d oc u m e ntati o n c o m pleti o n a n d rete nti o n, a n d acc urate st u d y dr u g acc o u nta bilit y. 
T o  t his e n d, t he C R A will visit t he st u d y site at s uita ble i nter vals a n d b e i n fre q ue nt c o ntact 
t hr o u g h v er bal a n d writte n c o m m u nicati o n. T he I n vesti gat or will gra nt access t o all 
d oc u me nts (relat e d t o t he st u d y a n d t he i n di vi d ual partici pa nts) at a n y ti me t hese are 
re q ueste d. I n t ur n, t he C R A will a d here t o all re q uire me nts f or partici pa nt c o nfi de ntialit y as 
o utli ne d i n t he i nf or me d c o nse nt f or m (I C F). T h e I n v esti gat or a n d I n v esti gat or’s staff will be 
e x pecte d t o c o o per ate wit h t he C R A, t o be a vaila b le d uri n g a p orti o n of t he m o nit ori n g visit 
t o a ns wer q uesti o ns, a n d t o pr o vi de a n y missi n g i nf or mati o n. 
9. 1. 6  
Q u alit y Ass ur a nce a n d Q u alit y C o ntr ol 
Eac h cli nical site will perf or m i nter nal q ualit y ma na ge me nt of st u d y c o n d u ct, data a n d 
bi ol o gical s peci me n c ollec ti o n, d oc u me ntati o n, a n d c o m pleti o n. A n i n di vi d ualize d q ualit y 
ma na ge me nt pla n ma y b e de vel o pe d t o d escri be a site’s q ualit y ma na ge me nt. 
9. 1. 7  
Rec or ds  
T he res ults fr o m Scr ee ni n g a n d d ata c ollecte d d uri n g t he st u d y will be rec or de d i n t he 
s u bject’s e C R F. T o mai ntai n c o nfi de ntialit y, t he s u bjects will be i de ntifie d o nl y b y n u m bers. 
T he c o m plete d e C R Fs will be tra nsferre d t o t he S p o ns or or desi g nee. C o pies of eac h e C R F 
will be retai ne d b y t he PI. All s o urce d oc u me nts, rec or ds, a n d re p orts will b e retai ne d b y t h e 
cli nic. 
All pri mar y s o urce d ata or c o pies t here of (e. g., la b orat or y rec or ds, e C R Fs, data s heets, 
c orres p o n d e nce, p h ot o gr a p hs, a n d c o m p uter rec or ds) t hat are a res ult of t he ori gi nal 
o bser vati o ns a n d acti vities of t he st u d y a n d are necessar y f or t he rec o nstr ucti o n a n d 
e val uati o n of a n y st u d y r e p ort will be retai n e d i n t he cli nic arc hi ves.  
S p o ns or will i nf or m t he PI of t he ti me p eri o d  f or retai ni n g t h ese rec or ds t o c o m pl y wit h all 
a p plica ble r e g ulat or y r e q uire me nts. T he mi ni m u m rete nti o n ti me will meet t he strictest 
(l o n gest) st a n dar d a p plica ble t o t hat site f or t he st u d y, as di ctate d b y a n y i nstit uti o nal 
re q uire me nts or l o cal la ws or re g ulati o ns, or S p o ns or sta n dar ds/ pr o ce d ures; ot her wise, t he 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 9 2  of 9 6  
rete nti o n peri o d will def a ult t o t he rete nti o n peri o d of 1 5 years f oll o wi n g c o m pleti o n of t he 
cli nical trial. 
Bl o o d a n d tiss ue sa m ples will be c ollecte d a n d a n y re mai ni n g or bac k- u p st u d y sa m ples ma y 
be use d f or f ut ure e x pl orat or y a n d bi o mar k er a n al ysis. T he sa m ples will be st ore d f or u p t o 
1 5 years.  
9. 1. 8  
Fi n a nci n g a n d I ns ur a nce  
T he fi na nci n g a n d i ns ura nce f or t his st u d y are o utli ne d i n t he Cli nical Trial A gree me nt. 
9. 1. 9  
P u blic ati o n P olic y  
N G M will retai n o w ners hi p of all data. All pr o p ose d p u blicati o ns base d o n t his st u d y will be 
s u bject t o s p o ns or’s a p pr o val re q uire m e nts. 
 
 
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 9 3  of 9 6  
1 0  
Refere nces  
1 0. 1  
List of S p o ns or's Cli nic al St u dies Refere nce d i n t his Pr ot oc ol  
St u d y N o.  
P h ase  
St u d y Title  
St u d y P o p ul ati o n  
St u d y 1 8 - 05 0 1 
1 
A P hase 1, M ultice nter, O pe n -La bel, 
Si n gle -D ose a n d M ulti ple -D os e Escalati o n 
St u d y of t he Safet y, T olera bilit y, a n d 
P har mac o ki netics of I ntra vitre al I nj ecti o ns of 
N G M 6 2 1 i n P atie nts wit h Ge o gra p hic 
Atr o p h y Sec o n dar y t o A ge -rel ate d Mac ular 
De ge nerati o n  
P atie nts wit h 
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  
1 0. 2  
List  of S p o ns or's N o ncli nic al St u dies Refere nce d i n t his Pr ot oc ol 
St u d y N o.  
St u d y Title  
St u d y  N G M6 2 1 - TX - 04 
A 2 8 -W ee k Re peat -D ose T o xicit y St u d y of N G M 6 2 1 i n C y n o m ol g us 
M o n ke ys wit h a 1 2 -W ee k Rec o ver y P eri o d  
1 0. 3  
Liter a t ure Ref ere nces 
B o yer D S, Sc h mi dt- Erf urt h U, va n L o o kere n Ca m pa g ne M, et al. T he pat h o p h ysi ol o g y of 
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 n d t he c o m ple me nt 
pat h wa y as a t hera pe utic tar get. Reti na. 2 0 1 7 Ma y; 3 7: 8 1 9 – 3 5. 
Da nis R P, La vi ne J A, D o mal pall y A. Ge o gra p hic atr o p h y i n patie nts wit h a d va nce d dr y a ge- 
relate d mac ular de ge nerati o n: c urre nt c halle n ges a n d f ut ure pr os pects. Cli n O p ht hal m ol. 
2 0 1 5 N o v 2 0; 9: 2 1 5 9 – 7 4. 
Ferris F L, III, Fi ne S L, H y ma n L. A ge-relate d mac ular de ge nerati o n a n d bli n d ness d ue t o 
ne o vasc ular mac ul o pat h y. Arc h. O p ht hal m ol 1 9 8 4; 1 0 2( 1 1): 1 6 4 0 – 2. 
H olz  FG,  Sc h mitz- Valc ke n ber g S, Flec ke nstei n M. Rece nt de vel o p me nts in  the treat m e nt of 
a ge-relate d mac ular de ge nerati o n. J Cli n I n vest. 2 0 1 4 A pr; 1 2 4( 4): 1 4 3 0 – 8. 
H olz F G, Sa d da S R, B us bee B, et al. Efficac y a n d safet y of la m paliz u ma b f or ge o gra p hic 
atr o p h y d ue t o a ge-r elate d mac ular de ge nerati o n: c hr o ma a n d s pectri P hase 3 ra n d o mize d 
cli nical trials. J A M A O p ht hal m ol. 2 0 1 8 J u n 1; 1 3 6: 6 6 6 – 7 7. 
I V R E C bi o. bi o, I nc. 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, me t its 
pr i mar y e n d p oi nt a n d reac he d statistical sig 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 dry a g e-relate d ma c ular de ge nerati o n 
[I nter net]. 2 0 1 9 [cite d 2 0 2 0 Fe b 2 4]. A vaila ble fr o m: 
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-c5 -i n hi bit or- met-its 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 9 4  of 9 6  
Ja bs DA , N usse n blatt R B , R ose n ba u m J T, et al. Sta n dar dizati o n of u veitis n o me nclat ure f or 
re p orti n g cli nical data. Res ults of t he First I nter nati o nal W or ks h o p. A m J O p ht hal m ol. 2 0 0 5 
Se p; 1 4 0: 5 0 9 – 1 6. 
Ka n dasa m y  R, Wic kre masi n g he S, Gu y mer  R. Ne w Treat me nt Mo dalities  for  Ge o gra p hic 
Atr o p h y. Asia Pac J O p ht hal m ol ( P hila). 2 0 1 7 N o v- Dec; 6: 5 0 8 – 1 3. 
N C T 0 0 9 3 5 8 8 3 Cli nical Trials. g o v, Ale xi o n P har mace uticals. C o m ple me nt i n hi biti o n wit h 
ec uliz u ma b f or t he treat me nt of  n o n-e x u dati ve ma c ular de ge nerati o n  ( AM D) ( C O M P L E T E) 
[I nter net]. 2 0 1 9 [cite d 2 0 1 9 Fe b 1 5]. A vaila ble fr o m: 
htt ps://cli nicaltrials. g o v/ct 2/s h o w/ N C T 0 0 9 3 5 8 8 3 
N C T 0 1 5 2 7 5 0 0 Cli nical Trials. g o v, N o vartis P har mace uticals. I ntra vitreal L F G 3 1 6 i n pa tie nts 
wit h a ge-r elate d ma c ular de ge nerati o n ( A M D) [I nter net]. 2 0 1 8 [cite d 2 0 1 8 A u g 2 9]. 
A vaila ble  fr o m: htt ps://cli nicaltrials. g o v/ct 2/s h o w/ N C T 0 1 5 2 7 5 0 0 
N C T 0 2 5 0 3 3 3 2 Cli nical Trials. g o v, A pellis P har mace uticals, I nc. St u d y of of AP L - 2 t hera p y 
i n patie nts ge o gra p hi c atr o p h y ( FI L L Y) [I nter net]. 2 0 1 9 [cite d 2 0 1 9 Fe b 1 5]. A vaila ble fr o m: 
htt ps://cli nicaltrials. g o v/ct 2/s h o w/ N C T 0 2 5 0 3 3 3 2 
N C T 0 2 6 8 6 6 5 8 Cli nical Trials. g o v, O p ht h otec h C or p orati o n. Zi m ura i n s ubjects  wi t h 
ge o gra p hi c atr o p h y sec o n dar y to  dr y a ge -relate d ma c ular de ge nerati o n [I nter net]. 2 0 1 9 [cite d 
2 0 1 8 A u g 2 9]. A vaila ble fr o m: htt ps://cli nicaltrials. g o v/ct 2/s h o w/ N C T 0 2 6 8 6 6 5 8 
N usse n blatt R B, Palesti ne A G, C ha n C C, et al. Sta n dar dizati o n of vitreal i nfla m mat or y 
acti vit y i n i nter mediate a n d p osteri or u veitis. O p ht hal m ol o g y 1 9 8 5; 9 2: 4 6 7 – 7 1. 
Par k D H, C o n n or K M, La m bris J D. T he c halle n ges a nd  pr o mise  of c om ple me nt t h era pe utics 
f or ocular  diseases. Fr o nt I m m u n ol. 2 0 1 9 Ma y 1 5; 1 0: 1 0 0 7. 
Sa h u A, La m bris J D. Str uct ure a n d bi ol o g y of c o m ple me nt pr otei n C 3, a c o n necti n g li n k 
bet wee n i n nate a n d ac q uire d i m m u nit y. I m m u n ol Re v. 2 0 0 1 A pr; 1 8 0: 3 5 – 4 8. 
Si n g h R P. FI L L Y. A P L- 2  (pe gcetac o pla n)  ge o gra p hic atr o p h y pr eli mi nar y  18 - m o nt h res ults. 
Prese nte d  at: Mac ula S ociet y a nn ual  meeti n g; Fe b. 21 - 2 4, 2 0 1 8; Be verl y Hills, Calif or nia. 
va n L o o kere n Ca m pa g ne M, Wies ma n n C, Br o w n EJ. Macr o p ha ge c o m ple me nt rece pt ors 
a n d pat h o ge n cleara nce. Cell Micr o bi ol. 2 0 0 7 Se p; 9( 9): 2 0 9 5 – 1 0 2 
W o n g W L, S u X, Li X, et al. G l o bal pre vale nce of age-r elate d mac ular de ge nerati o n a nd 
disease b ur de n pr ojecti o n f or 2 0 2 0 a n d 2 0 4 0; a s yste matic re vie w a n d meta-anal ysis.  La ncet 
2 0 1 4; 2:e 1 0 6 – 1 6. 
Ye h os h ua Z, de A m ori m Garcia Fil h o C A, N u nes R P, et al. Syste mic  c o m ple me nt i n hi biti o n 
wit h  ec uliz u ma b  f or ge o gra p hic atr o p h y i n a ge-relate d mac ular de ge nerati o n: the 
C O M P L E T E st u d y. O p ht hal m ol o g y. 2 0 1 4 Mar; 1 2 1: 6 9 3– 7 0 1. 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 9 5  of 9 6  
1 1  A p pe n dices  
A p pe n di x  1. Gr a di n g Sc ales  
1 1. 1  
Gr a di n g Sc ale f or A nteri or C h a m ber Fl are or Cells  
Fl are  
Gr a de  
Descri pti o n  
0  
N o ne  
1 +  
Fai nt  
2 +  
M o derate (iris a n d le ns d etails clear)  
3 +  
Mar ke d (iris a n d le ns det ails haz y)  
4 +  
I nte ns e (fi bri n or plastic a q ue o us) 
 
 
Cells  
Gr a de  
Cells i n Fiel d [ 1] 
0  
< 1  
0. 5 +  
1 – 5  
1 +  
6 – 1 5  
2 +  
1 6 – 2 5  
3 +  
2 6 – 5 0  
4 +  
>  5 0  
1-Fiel d size is a 1 m m b y 1 m m slit bea m  
 
1 1. 2  
Gr a di n g Sc ale f or Vitre o us Cells  
Cells  
Gr a de  
Cells per H P F  
0  
0 – 1  
Trace  
2 – 2 0  
1  
2 1 – 5 0  
2  
5 1 – 1 0 0  
3  
1 0 1 – 2 5 0  
4  
> 2 5 0  
C G  
Ca n n ot gr a de  
N D  
N ot d o ne  
 

N G M 6 2 1  
N G M 6 2 1 -G A -2 0 1 Pr ot oc ol v 5 . 0, 1 3  Ma y 2 0 2 1  
N G M Bi o p har mace uticals, I nc.  
C o nfi de ntial  
P a ge 9 6  of 9 6  
1 1. 3  
Gr a di n g Sc ale f or Vitre o us H aze  
Cells  
Gr a de  
Cells i n Fiel d [ 1] 
0  
N o i nfla m mati o n  
+ 0. 5  
Trace i nfla m mati o n (sli g ht bl urri n g of t he o ptic disc mar gi ns a n d/ or 
l oss of N F L r efle x)  
+ 1  
Mil d bl urri n g of r eti nal vessels a n d o ptic ner v e  
+ 2  
M o derate bl urri n g of o ptic ner ve h ea d  
+ 3  
Mar ke d bl urri n g of o ptic ner ve hea d  
+ 4  
O ptic ner ve h ea d n ot visi ble  
[ 1] Discrete de bris, s uc h as fr o m a P V D, is n ot i ncl u de d i n t he gr a di n g of i nfl a m m ati o n.  
Av oi d t he i m p ulse t o gr a de de bris as tr ace.