Double-Blind, Randomized, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of LT3001 Drug Product and Drug-Drug Interaction in Healthy Adult Subjects
Phase: PHASE1
Conditions: Acute Ischemic Stroke
Sponsor: Lumosa Therapeutics Co., Ltd.

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 1  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
Title Pa ge  
Pr ot oc ol Title:   
A D o u ble -Bli n d, Ra n d o mize d, Place b o -C o ntr olle d, P hase 1 
St u d y 
t o 
E val uate 
t he 
Safet y, 
T olera bilit y, 
a n d 
P har mac o ki netics of 
M ulti ple 
D oses of L T 3 0 0 1 
Dr u g 
Pr o d uct a n d Dr u g -Dr u g I nteracti o n i n Healt h y A d ult S u bjects  
Pr ot oc ol N u m ber:   
L T 3 0 0 1 -1 0 5  
 
 
   
 
  
 
 
 
 
 
 
 
 
 
 
 
 
C o nfi de nti alit y St ate me nt  
T he i nf or mati o n i n t his d oc u me nt c o ntai ns tra de secrets a n d c o m mercial i nf or mati o n t hat are pri vile ge d or c o nfi de ntial a n d ma y n ot be discl ose d 
u nless s uc h discl os ure is re q uire d b y a p plica ble la w or re g ulati o ns. I n a n y e ve nt, pers o ns t o w h o m t he i nf or mati o n is discl ose d m ust be i nf or me d 
t hat t he i nf or mati o n is privile ge d  or c o nfi de nti al  a n d ma y n ot be f urt her discl ose d b y t he m. T hese restricti o ns o n discl os ure will a p pl y e q uall y t o 
all  f ut ure i nf or mati o n s u p plie d t o y o u t hat is i n dicate d as privile ge d  or co nfi de nti al . 
 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 2  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
Pr ot oc ol A me n d me nt S u m m ar y of C h a n ges T a ble  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
. 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 3  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 4  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
i. 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
. 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
  
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 7  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 8  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 9  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 1 1  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
S T U D Y A D MI NI S T R A TI O N  
St u d y R ole  
N a me, title, c o nt act i nf or m ati o n  
 
 
 
 
 
  
 
 
 
 
  
  
 
 
 
  
 
 
 
 
 
 
 
 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 1 2  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
T a ble of C o nte nts  
 
1.  
S y n o psis ..........................................................................................................................1 5  
2.  
Sc he d ule of Acti vit ies ( S o A) .........................................................................................2 3  
3.  
I ntr o d ucti o n ...................................................................................................................3 6  
3. 1.  
St u d y Rati o nale  ...............................................................................................................3 6  
3. 2.  
Bac k gr o u n d  .....................................................................................................................3 6  
3. 2. 1.  
N o ncli nical St u dies  .........................................................................................................3 7  
3. 2. 2.  
Cli nical St u dies  ...............................................................................................................3 9  
3. 2. 3.  
Safet y  ..............................................................................................................................4 0  
3. 3.  
Be nefit/ Ris k Assess me nt  ................................................................................................4 0  
4.  
O bjecti ves a n d E n d p oi nts  ............................................................................................4 1  
5.  
St u d y Desi g n  ..................................................................................................................4 2  
5. 1.  
O verall Desi g n  ................................................................................................................4 2  
5. 2.  
Partici pa nt a n d St u d y C o m pleti o n  ..................................................................................4 6  
5. 3.  
E n d of St u d y Defi niti o n  ..................................................................................................4 6  
5. 4.  
Scie ntific Rati o nale f or St u d y Desi g n  ............................................................................4 6  
5. 5.  
J ustificati o n f or D ose ......................................................................................................4 6  
6.  
St u d y P o p ul ati o n  ...........................................................................................................4 7  
6. 1.  
I n cl usi o n Criteria  ............................................................................................................4 7  
6. 2.  
E xcl usi o n Criteria  ...........................................................................................................4 8  
6. 3.  
Lifest yle Restricti o ns  ......................................................................................................4 9  
6. 3. 1.  
Meals a n d Dietar y Restri cti o ns  .......................................................................................4 9  
6. 3. 2.  
Caffei ne, Al c o h ol, a n d T o bacc o  .....................................................................................4 9  
6. 3. 3.  
Acti vit y  ...........................................................................................................................4 9  
6. 4.  
Scree n Fail ures  ................................................................................................................4 9  
7.  
Tre at me nts  .....................................................................................................................5 0  
7. 1.  
Treat me nts A d mi nistere d  ................................................................................................5 0  
7. 2.  
L T 3 0 0 1 Dr u g Pr o d uct a n d Place b o  ................................................................................5 0  
7. 3.  
D ose M o dificati o n  ..........................................................................................................5 1  
7. 4.  
Met h o d of Treat me nt Assi g n me nt  ..................................................................................5 1  
7. 5.  
Ra n d o mizati o n Pr oce d ures  .............................................................................................5 1  
7. 6.  
Mai nte na nce of Ra n d o mizati o n C o des  ...........................................................................5 1  
7. 7.  
Bli n di n g  ..........................................................................................................................5 1  
7. 8.  
Brea ki n g t he Bli n d  ..........................................................................................................5 2  
7. 9.  
Pre pa rati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y ................................................................5 2  
7. 1 0.  
Treat me nt C o m plia nce  ....................................................................................................5 4  
7. 1 1.  
C o nc o mita nt T hera p y  .....................................................................................................5 4  
7. 1 1. 1.  Resc ue Me dici ne  .............................................................................................................5 4  
7. 1 2.  
Treat me nt after t he E n d of t he St u d y  ..............................................................................5 4  
8.  
Disc o nti n u ati o n/ Wit h dr a w al Criteri a  .........................................................................5 5  

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 1 3  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
8. 1.  
Disc o nti n uati o n of St u d y Treat me nt  ...............................................................................5 5  
8. 1. 1.  
Te m p orar y Dis c o nti n uati o n  ............................................................................................5 5  
8. 1. 2.  
Rec halle n ge  .....................................................................................................................5 5  
8. 2.  
Wit h dra wal fr o m t he St u d y .............................................................................................5 5  
8. 3.  
L ost t o F oll o w U p  ...........................................................................................................5 6  
8. 4.  
Re place me nts  ..................................................................................................................5 7  
9.  
St u d y Assess m e nts a n d Pr oce d ures .............................................................................5 8  
9. 1.  
A d verse E v e nts  ...............................................................................................................5 9  
9. 1. 1.  
Ti me Peri o d a n d Fre q ue n c y f or C ollecti n g A E a n d S A E 
I nf or mati o n .....................................................................................................................5 9  
9. 1. 2.  
Met h o d of Detecti n g A Es a n d S A Es  ..............................................................................6 0  
9. 1. 3.  
F oll o w -u p of A Es a n d S A Es  ...........................................................................................6 0  
9. 1. 4.  
Re g ulat or y Re p orti n g Re q uire me nts f or S A E s ...............................................................6 0  
9. 1. 5.  
Pre g na nc y  ........................................................................................................................6 0  
9. 2.  
Treat me nt of O v er d ose  ...................................................................................................6 1  
9. 3.  
Safet y Assess me nts  .........................................................................................................6 1  
9. 3. 1.  
P h ysical E xa mi nati o ns  ....................................................................................................6 1  
9. 3. 2.  
Vital Si g ns  .......................................................................................................................6 1  
9. 3. 3.  
Electr ocar di o gra ms  .........................................................................................................6 2  
9. 3. 4.  
P ulse O xi metr y ................................................................................................................6 2  
9. 3. 5.  
C oa g u lati o n a n d Platelet F u ncti o n  Test  ..........................................................................6 2  
9. 3. 6.  
Cli nical Safet y La b orat or y Assess me nts  ........................................................................6 2  
9. 4.  
P har mac o ki netics  ............................................................................................................6 3  
9. 5.  
P har mac o ge n etics  ...........................................................................................................6 4  
9. 6.  
Me dical  Res o urce Utilizati o n a n d Healt h Ec o n o mi cs  ....................................................6 4  
1 0.  
St atistic al C o nsi der ati o ns  .............................................................................................6 5  
1 0. 1.  
Sa m ple Size Deter mi nati o n  ............................................................................................6 5  
1 0 . 2. 
P o p ulati o ns f or A nal yses  ................................................................................................6 5  
1 0. 3.  
Statistical A nal yses  .........................................................................................................6 5  
1 0. 3. 1.  Safet y A nal yses  ...............................................................................................................6 5  
1 0. 3. 2.  P har mac o ki netic A n al yses  ..............................................................................................6 6  
1 1.  
Refere nces  ......................................................................................................................6 8  
1 2.  
A p pe n dices  .....................................................................................................................7 0  
A p pe n di x 1: A b bre viati o ns a n d Ter ms  ..........................................................................................7 1  
A p pe n di x  2: Cli nical La b orat or y Tests  ..........................................................................................7 3  
A p pe n di x 3: St u d y G o ver na nce C o nsi derati o ns  ............................................................................7 5  
Re g ulat or y a n d Et hical C o nsi derati o ns  .................................................................................7 5  
Fi na ncial Discl os ur e  ..............................................................................................................7 5  
I nf or me d C o nse nt Pr ocess ....................................................................................................7 5  
Data Pr otecti o n  ......................................................................................................................7 6  
P u blicati o n P olic y  .................................................................................................................7 6  
Disse mi nati o n of Cli nical St u d y Data  ...................................................................................7 6  

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 1 4  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
Data Q ualit y Ass ur a nce  ........................................................................................................7 7  
S o urce D oc u m e nts  ................................................................................................................7 8  
St u d y a n d Site Cl os ure  ..........................................................................................................7 8  
A p pe n di x 4 : A d verse E v e nts: Defi niti o ns a n d Pr oce d ures f or Rec or di n g, 
E val uati n g, F oll o w -u p, a n d Re p orti n g  ............................................................................7 9  
A p pe n di x  5: C o ntrace pti ve G ui da n ce a n d C ollecti o n of Pre g na nc y 
I nf or mati o n .....................................................................................................................8 6  
Defi niti o ns  8 6  
C o ntrace pti o n G ui da nce  ........................................................................................................8 6  
C ollecti o n of Pre g na nc y I nf or mati o n  ....................................................................................8 8  
  
List of Ta bles  
Ta ble 1   
Sc he d ule of Acti vities f or Part A  ...................................................................... 2 3  
Ta ble 2   
Sc he d ule of Acti vities f or Part B, C o h ort 1  ...................................................... 2 6  
Ta ble 3   
Sc he d ule of Acti vities f or Part B, C o h ort 2  ...................................................... 2 8  
Ta ble 4   
Sc he d ule of Acti vities f or Part B, C o h or t 3 ...................................................... 3 1  
Ta ble 5   
Sc he d ule of Acti vities f or Part B, C o h ort 4  ...................................................... 3 4  
Ta ble 6   
I d e ntit y of St u d y Treat m e nts ............................................................................. 5 0  
Ta ble 7               T otal V ol u me of Bl o o d Per S u bject i n Eac h C o h ort  ......................................... 5 8  
Ta ble 8               Pr ot oc ol -Re q uire d Safet y La b orat or y Assess me nts  .......................................... 7 3  
Ta ble 9               Hi g hl y Effecti ve C o ntrace pti ve Met h o ds  .......................................................... 8 7  
 
List of Fi g ures  
Fi g ure 1  
St u d y Desi g n Sc he ma  ........................................................................................ 4 2  
Fi g ure 2  
D osi n g Sc he ma of L T 3 0 0 1 a n d As piri n C o -a d mi nistrati o n  .............................. 4 4  
Fi g ure 3  
D osi n g Sc he ma of L T 3 0 0 1 a n d Cl o pi d o grel C o -a d mi nistrati o n ...................... 4 5  
Fi g ure 4  
D osi n g Sc he ma of L T 3 0 0 1 a n d A pi xa ba n C o -a d mi nistrati o n .......................... 4 5  
Fi g ure 5  
D osi n g Sc he ma of L T 3 0 0 1 a n d Da bi gatra n C o -a d mi nistrati o n ........................ 4 6  
 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 1 8  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
T he re mai ni n g c o m bi nati o n treat me nts i n a se nti ne l s u bject ma y n ot pr ocee d i n t he e ve nt of a n y 
of t he f oll o wi n g:  
•  A s u bject e x perie n ces a n y se vere h e m orr h a ge w hi c h is assesse d as relate d t o t he 
c o m bi nati o n treat me nt  
•  A s u bject treate d wit h L T 3 0 0 1 dr u g pr o d uct e x perie nces a n y S A E relate d t o st u d y dr u g  
(at least p ossi bl y relate d)  
•  Safet y c o ncer ns per t he I n vesti gat or’s cli nical j u d g me nt 
T he d osi n g sc he ma is s u m marize d bel o w.  
E ac h C o h ort of P art B   
Se nti nel  S u bjects   
Re m ai ni n g S u bjects  
N u m ber of S u bjects  
3  
9  
 
I n C o h ort 1 , eac h s u bj ect will recei v e a si n gle 1 5-mi n ute i nf usi o n of L T 3 0 0 1 
 o n 
Da y  1. E ac h s u bject will recei ve m ulti ple -d ose as piri n  as f oll o ws: a l oa di n g d ose of 3 2 5 m g as piri n 
o n t he m or ni n g of D a y 2 f oll o we d b y a dail y mai nte na nce d ose of 8 1  m g as piri n o n D a ys 3 t hr o u g h 
8 . T he regi me n is i nte n de d t o ac hie ve its ma xi mal i n hi bit o r y effects o n platelet f u ncti o n. As piri n 
will be a d mi nist ere d after brea kfast.  O n t he m or ni n g of Da y 6 , t he d ose of as piri n will be  f oll o we d 
b y t he first d ose of L T 3 0 0 1 
 a d mi nistere d as a 1 5-mi n ute I V i nf usi o n. S u bjects will 
recei v e 9 d oses of L T 3 0 0 1 o n D a ys 6 t hr o u g h 8 (t hree d oses per da y wit h t hree h o urs bet wee n 
d oses ). Eac h s u bject will be a d mitte d i nt o t he st u d y site on Da y -1, sta y u ntil Da y 8 , a n d will ha ve 
a f oll o w-u p visit o n Da y 1 5 . 
I n C o h ort 2 , eac h s u bject will recei ve a si n gle 1 5 -mi n ute i nf usi o n of L T 3 0 0 1 
 o n 
Da y  1. E ac h s u bject will recei v e m ulti ple -d ose cl o pi d o grel  as f oll o ws: a l oa di n g d ose of 3 0 0  m g 
cl o pi d o grel o n Da y 2 f oll o we d b y a dail y mai nte na nce d ose of 7 5 m g cl o pi d o grel o n Da ys 3 
t hr o u g h 9 , a d osi n g para di g m c o nsiste nt wit h cli nical use i n rele va nt i n dicati o ns. Cl o pi d o grel will 
be a d mi nistere d aft er brea kfast.  O n D a y 7 , t he d ose of cl o pi d o grel will be f oll o we d b y t he first 
d ose of L T 3 0 0 1 
 a d mi nistere d as a 1 5-mi n ute I V i nf usi o n. S u bjects will recei ve 
9  d oses of L T 3 0 0 1 o n Da ys 7 t hr o u g h 9 (t hree d oses per da y wit h t hree h o urs bet wee n d oses). 
Eac h s u bject will be a d mitte d i nt o t he st u d y site o n Da y -1, sta y u ntil Da y 1 0 , a n d will ha ve a 
f oll o w-u p visit o n Da y 1 6 . 
I n C o h ort 3 , eac h s u bject will recei ve a si n gle 1 5 -mi n ute i nf usi o n of L T 3 0 0 1 
 o n 
Da y  1. E ac h s u bj ect will recei v e m ulti ple -d ose a pi xa ba n  as f oll o ws:  5 m g a pi xa ba n t wice dail y 
(BI D ) e v er y 1 2 h o urs ( q 1 2 h) o n Da ys 2 t hr o u g h 7 . T he m or ni n g d oses of a pi xa ba n will be gi ve n 
after brea kfast. Gi ve n t hat t he half-life of a pi xa ba n is 9 t o 1 4 h o urs, t he 3 -da y a pi xa ba n BI D 
treat me nt all o ws f or reac hi n g o ver 5 half -li ves a n d 9 7 % st ea d y stat e of a pi xa ba n bef ore t h e 
c oa d mi nistrati o n of a pi x a ba n a n d L T 3 0 0 1. O n Da y 5 , t h e first d ose of a pi xa ba n will b e  f oll o we d 
b y t he first d ose of L T 3 0 0 1
 a d mi nistere d as a 1 5-mi n ute I V i nf usi o n. S u bjects will 
recei v e 9 d os es of L T 3 0 0 1 o n Da ys 5 t o 7  (t hree d oses per da y wit h t hree h o urs bet wee n d oses). 
Eac h s u bject will b e a d mitte d i nt o t he st u d y site o n Da y -1, sta y u ntil Da y 8 , a n d will ha v e a f oll o w -
u p visit o n Da y 1 4 . 

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 2 0  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
St atistic al Met h o ds  
S a m ple Size Deter mi n ati o n:  
T here were n o statistical c o nsi derati o ns i n deter mi ni n g sa m ple size. T wel ve t o 1 6 s u bjects per 
treat me nt gr o u p is dee m e d t o be s ufficie nt t o meet t he st u d y o bjecti ves. 
S afet y A n al ysis:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
P h ar m ac o ki netic A n al ysis:  
Fr o m t he pl as m a  c o nce ntrati o n -ti me data, t he f oll o wi n g P K para meters will be deter mi ne d, as 
data pe r mit: 
C ma x  
Ma xi m u m plas ma c o nce ntrati o n  d uri n g a d osi n g i nter val  
C mi n  
Tr o u g h plas ma c o nce ntrati o n  
C a v 
Mea n stea d y -state dr u g c o nce ntrati o n 
tma x  
Ti me t o reac h t he o bser ve d ma xi m u m ( pea k) c o nce ntrati o n  
λ z 
A p pare nt first -or der ter mi nal eli mi nati o n rate c o nsta nt, calc ulate d b y li near least -
s q uares re gressi o n a nal ysis o n t he ter mi nal l o g-li near p hase of t he plas ma 
c o nce ntrati o n vs ti me c ur ves usi n g at least 3 ti me p oi nts  
A U C 0 -∞  
Area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o i nfi nit y, 
calc ulate d as A U C 0 -t + C t / λz, w here Ct is t he last meas ura ble c o nce ntrati o n 
A U C 0 -t  
Area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o t he ti me of last 
q ua ntifia ble c o nce ntrati o n, calc ulate d b y t he li near tra pez oi dal li near i nter p olati o n 
met h o d  

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 2 1  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
A U C 0 -ta u  
A U C o ver t he d osi n g  i nter val τ at stea d y-state 
M R T
0 -∞ 
Mea n resi de nce ti me, calc ulate d as 
𝐴𝑈𝑀𝐶0 −𝜏 +  τ (𝐴𝑈𝐶0 −∝ − 𝐴𝑈𝐶0 −𝜏) 
𝐴𝑈𝐶0 −𝜏
−
𝑇𝐼
2  w here 
A U M C 0 -τ is t he area u n der t he m o me nt c ur ve o ver d osi n g i nter val τ, TI re prese nts 
i nf usi o n d urati o n. 
t1/ 2 
Eli mi nati o n half -life, calc ulate d as 0. 6 9 3 / λ z 
C L  
T otal b o d y cleara nce of t he dr u g fr o m plas ma, calc ulate d as D ose / A U C 0 -∞ 
V z 
A p pare nt v ol u me of distri b uti o n d uri n g t he ter mi nal p hase, calc ulate d as ( D ose / 
A U C 0 -∞) / λ z 
V ss 
A p pare nt v ol u me of distri b uti o n d uri n g stea d y state, calc ulate d as C L   M R T  
 
 
 
 
 
 
 
 
 
 
Fr o m t he uri ne  c o nce ntrati o n data, t he f oll o wi n g P K para meters will be d eter mi ne d, as d ata p er mit:  
Ae x -y  
A m o u nt of dr u g e xcrete d i n uri ne wit hi n a c ollecti o n i nter val ( x t o y  h o urs), w here t he 
val ues of x t o y are 0 t o 1 2 a n d 1 2 t o 2 4  
Ae 0 -2 4  
T otal a m o u nt of dr u g e xcrete d i n uri ne o ver t he e ntire c ollecti o n peri o d ( 0 t o 
2 4  h o urs)  
Fe 0 -2 4  
Fracti o n e xcrete d i n uri ne fr o m 0  t o 2 4 h o urs after d osi n g, calc ulate d as Ae0 -2 4 / D ose 
× 1 0 0  
C Lr  
Re nal cleara nce, calc ulate d as Ae 0 -2 4 / A U C0 -∞ 
Uri ne P K para meters will be liste d b y s u bject a n d treat me nt a n d s u m marize d b y treat me nt usi n g 
t he P K A S a n d t he f oll o wi n g s u m mar y statistics: n, arit h metic mea n, S D, C V, mi ni m u m, me dia n, 
a n d ma xi m u m.  
P h ar m ac o ki netic/ S afet y A n al yses  
P har mac o ki netic a n d safet y para meters of s p ecial i nterest will be assesse d descri pti vel y w he ne ver 
p ossi ble a n d b y e x pl orat or y statistical c o m paris o ns a n d re q uire d pl ots of t he p ote ntial P K -safet y 
relati o ns hi p bet wee n L T 3 0 0 1 le vels i n plas m a a n d all a p plica ble safet y para meters (a bs ol ute a n d/ or 
baseli ne a dj uste d) will be prese nte d.  

C O N FI D E N TI A L  
 L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 2 2  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
C O N FI D E N TI AL  
Dr u g/ Dr u g I nteracti o ns  
T he effect of as piri n, cl o pi d o grel, a pi xa ba n or da bi gatra n o n t he P K of L T 3 0 0 1 as well as t he effect 
of L T 3 0 0 1 o n t he P K of as piri n, cl o pi d o grel, a pi xa ba n or da bi gatra n will be assesse d b y c o m p ari n g 
stea d y-state P K para meters of L T 3 0 0 1 a n d t hese c o nc o mita nt medicati o ns.  
 

C O N FI D E N TI A L  
 
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 2 5  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
n. 
P K uri ne  sa m ples will be 
 
 
o   
All s u bjects w h o recei ve at least o ne d ose will c o m plete t he e n d -of -st u d y (E O S ) visit ( wit hi n 3 t o 7 2 h o urs after t he last st u d y dr u g a d mi nistrati o n).  
p   
A 3 0 -mi n ute wi n d o w is all o we d f or n o n -P K pr oce d ures  
q   
P h ysical e xa mi nati o n will be perf or me d at scree ni n g visit, pre d ose o n Da y 1, Da y 2 a n d Da y 3 a n d Da y 4.  
r. 
Platelet f u ncti o n test will be meas ure d at pre -d ose o n Da y -1.  
s. 
Platelet f u ncti o n test will be meas ure d o n t he first d ose of L T 3 0 0 1 at 1 5 mi n after i nf usi o n is i nitiate d (e n d of i nf usi o n) o n Da y 1.  
t. 
Platelet f u ncti o n test will be meas ure d o n t he last d ose of L T 3 0 0 1 at 1 5 mi n afte r i nf usi o n is i nitiate d (e n d of i nf usi o n) o n Da y 3. 
 

C O N FI D E N TI A L  
 
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 2 7  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
a   
Vir ol o g y tests will i ncl u de HI V a nti b o d y, H Bs A g, he patitis C vir us a nti b o d y , a n d C O VI D -1 9  a nti b o d y. 
b   
De m o gra p hics will i ncl u de  a ge, ge n der, hei g ht, b o d y wei g ht, b o d y mass i n de x ( B MI ) a n d race. O n Da y -1 , o nl y b o d y wei g ht will be meas ure d.  
c   
Ser u m pre g na nc y test will be perf or me d i n fe male s u bjects of c hil d beari n g p ote ntial  wit hi n 2 4 h o urs pri or t o t he first dr u g treat me nt o n Da y 1.  
d   
S u bjects will recei ve as piri n after brea kfast. T he d ose of as piri n o n Da y 6 , Da y 7 a n d Da y 8 will be f oll o we d i m me diatel y b y 
 L T 3 0 0 1 a d mi nistere d as a 
1 5 -mi n ute I V i nf usi o n.  
e   
P h ysical e xa mi nati o n will be perf or me d at scree ni n g visit, pre d ose o n Da y 1, t he e n d of as piri n si n gle treat me nt o n Da y 5 , t he e n d of c o m bi nati o n treat me nt o n Da y 8 
a n d f oll o w -u p visit o n Da y 1 5  
f   
Vital si g ns will i ncl u de b o d y te m perat ure, bl o o d press ure, res pirat or y rate, a n d heart rate. Meas ure me nts will be ma de after t he s u bject has reste d i n a s u pi ne p ositi o n 
f or at least 3 mi n utes. Bl o o d press ure will be assesse d i n seate d a n d s u pi ne p ositi o n at pre d ose a n d 6 0 mi n utes after d osi n g/i nf usi o n, o nl y s u pi ne p ositi o n at 2 0 mi n utes 
after d osi n g/i nf usi o n. Vital si g ns will be assesse d at scree ni n g visit, Da y 1 t o 5 ( pre-d ose), Da y 6 t o Da y 8 (eac h L T 3 0 0 1 d osi n g peri o d at pre-d ose, 2 0 mi n utes a n d 6 0 
mi n utes  after i nf usi o n is i nitiate d), a n d f oll o w -u p visit o n Da y 1 5 . 
g   
A 1 2 -lea d E C G assess me nt will be perf or me d at scree ni n g visit
 
  
h   
P K bl o o d sa m ples of L T 3 0 0 1 will be c ollecte d 
 
 
 
 
i   
P K bl o o d sa m ples of L T 3 0 0 1 will be c ollec  
  
 
 
  
   
 
 
 
  
j   
P K bl o o d sa m ples of as piri n will be c ollecte d
 
p ost d ose.  
k. 
Platelet f u ncti o n test a n d c oa g ulati o n test will be meas ure d
 
 
l. 
Platelet f u ncti o n test a n d c oa g ulati o n test  will be meas ure d o n t he first d ose of L T 3 0 0 1 at 1 5 mi n after i n f usi o n is i nitiate d (e n d of i nf usi o n) o n Da y 6 . 
m.  
Platelet f u ncti o n test a n d c oa g ulati o n test  will be meas ure d o n t he last d ose of L T 3 0 0 1 at 1 5 mi n after i nf usi o n is i nitiate d (e n d of i nf usi o n) o n Da y 8 . 
n   
C oa g ulati o n para meters will i ncl u de P T, I N R, a P T T, a n d  T T . 
o   
He mat ol o g y tests will i ncl u de H b, R B C, M C V, Hct, M C H, W B C, W B C -D C, a n d platelets.  
p   
Cli nical c he mistr y tests will i ncl u de B U N, creati ni ne, fasti n g bl o o d gl uc ose, A L P, A L T, A S T, G G T, t otal bilir u bi n, t otal pr ot ei ns, al b u mi n/ gl o b uli n rati o, Na, K, Cl, Ca, 
bicar b o nate, uric aci d, C K, c h olester ol, tri gl yceri des, free ir o n, a n d ferriti n.  
q   
Uri nal ysis will i ncl u de di pstic k uri nal ysis a n d micr osc o pic e xa mi nati o n.  
r   
W he n t he uri ne dr u g/ c oti ni ne /alc o h ol tests a n d/ or cli nical la b orat or y tests i ncl u di n g c oa g ulati o n, he mat ol o g y a n d cli nical c he mistr y are perf or me d o n Da y -4 t o Da y -2 , 
t hese tests nee d n ot be re peate d o n Da y -1.  
s   
I n t he e ve nt of earl y ter mi nati o n ( E T), a ra n d o mize d s u bject will c o m plete t he E T pr oce d ures. Base d o n t he I n vesti gat or’s discreti o n, t he c ollecti o n of P K bl o o d 
sa m ples of L T 3 0 0 1 a n d/ or as piri n ca n be e xe m pte d if t he s u bject di d n ot recei ve t he i n dicate d st u d y dr u g.  
t   
A si n gle d ose of L T 3 0 0 1 dr u g pr o d uct will be gi ve n o n Da y 1  
u   
A 3 0 -mi n ute wi n d o w is all o we d f or n o n -P K pr oce d ures  

C O N FI D E N TI A L  
 
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 2 8  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
T a ble 3   
Sc he d ule of Acti vities f or P art B, C o h ort 2  
Pr oce d ures  
Scree ni n g Peri o d  
Tre at me nt Peri o d  
F oll o w -
u p  
E T s 
D a y -3 0 t o -2  D a y -1  D a y 1  D a y 2  D a y 3  D a y 4  D a y 5  D a y 6   
D a y 7   
D a y 8   
D a y 9   
D a y 1 0  D a y 1 6  
+/ - 1  
H o ur u  
1   
2 5   
4 9   
7 3   
9 7   
1 2 1   
1 4 5  1 4 8  1 5 1  1 6 9  1 7 2  1 7 5  1 9 3  1 9 6  1 9 9   
2 1 7  
I nf or me d c o nse nt 
X   
 
 
  
  
  
  
  
 
 
 
 
  
 
Uri ne dr u g/ c oti ni ne /alc o h ol test  
X   
X r 
 
  
  
  
  
  
 
 
 
 
  
 
Vir ol o g y test a 
X   
 
 
  
  
  
  
  
 
 
 
 
  
 
De m o gra p hics b 
X   
X  
 
  
  
  
  
  
 
 
 
 
  
 
Me dical a n d s ur gical hist or y  
X   
 
 
  
  
  
  
  
 
 
 
 
  
 
C hec k I n  
  
X  
 
  
  
  
  
  
 
 
 
 
  
 
Ser u m pre g na nc y test c 
  
X  
 
  
  
  
  
  
 
 
 
 
  
 
C Y P 2 C 1 9 ge n ot y pi n g  
X   
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
  
 
Cl o pi d o grel  d 
  
 
 
X   
X   
X   
X   
X   
X   
  
  
X   
  
  
X   
  
 
 
  
 
L T 3 0 0 1 dr u g pr o d uct  
  
 
X t 
  
  
  
  
  
X   
X   
X   
X   
X   
X   
X   
X   
X  
 
  
 
P h ysical e xa mi nati o n e 
X   
 
X  
  
  
  
  
X   
  
  
  
  
  
  
  
  
X  
 
X   
X  
Vital si g n  f 
X   
  X  
X  
  X   
  X   
  X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
X   
X  
 
X   
X  
1 2 -lea d E C G assess me nt g 
X   
 X    
X  
  X   
X   
X   
X   
X   
X   
  
  
X   
  
  
X   
  
 
 
X   
X  
P K bl o o d sa m ple of L T 3 0 0 1   
 
P K bl o o d sa m ple of cl o pi d o grel  j  
 
Platelet fu nc ti o n test 
  
X  k 
 
  
  
  
  
X  k  
X  l  
  
  
  
  
  
  
  
X  m  
 
X   
X  
C oa g ulati o n n 
X   
X r 
 
  
  
  
  
X k    
X l  
  
  
  
  
  
X  m  
 
X   
X  
He mat ol o g y test o 
X   
X  r 
 
  
  
  
  
X    
 
  
  
  
X  
 
X   
X  
Cli nical c he mistr y test  p 
 X   
X  r 
 
  
  
  
  
X    
 
  
  
  
X  
 
X   
X  
Uri nal ysis  q 
X   
X  r 
 
  
  
  
  
X    
 
  
  
  
X  
 
X   
X  
Disc har ge  
  
 
 
  
  
  
  
  
 
 
 
X  
  
 
Pri or a n d c o nc o mita nt me dicati o n   
X  
 
X  
A d verse e ve nt  
 
 
X  

C O N FI D E N TI A L  
 
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 2 9  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
E C G = electr ocar di o gra m; E T = earl y ter mi nati o n; P K = p har mac o ki netic  
a   
Vir ol o g y tests will i ncl u de HI V a nti b o d y, H Bs A g, he patitis C vir us a nti b o d y , a n d C O VI D -1 9  a nti b o d y. 
b   
De m o gra p hics will i ncl u de  a ge, ge n der, hei g ht, b o d y wei g ht, B MI a n d race. O n Da y -1 , o nl y b o d y wei g ht will be meas ure d.  
c   
Ser u m pre g na nc y test will be perf or me d i n fe male s u bjects of c hil d beari n g p ote ntial  wit hi n 2 4 h o urs pri or t o t he first dr u g treat me nt o n Da y 1.  
d   
T he d ose of cl o pi d o grel o n Da y 7 , Da y 8 a n d Da y 9 will be f oll o we d i m me diatel y b y
 L T 3 0 0 1 a d mi nistere d as a 1 5-mi n ute I V i nf usi o n.  
e   
P h ysical e xa mi nati o n will be perf or me d at scree ni n g visit, pre -d ose o n Da y 1, t he e n d of cl o pi d o grel si n gle treat me nt o n Da y 6 , t he e n d of c o m bi nati o n treat me nt o n 
Da y 9 a n d f oll o w -u p visit o n Da y 1 6 . 
f   
Vital si g ns will i ncl u de b o d y te m perat ure, bl o o d press ure, res pirat or y rate, a n d heart rate. Meas ure me nts will be ma de after t he s u bject has reste d i n a s u pi ne p ositi o n 
f or at least 3 mi n utes. Bl o o d press ure will be assesse d i n seate d a n d s u pi ne p ositi o n a t pre d ose a n d 6 0 mi n utes after d osi n g/i nf usi o n, o nl y s u pi ne p ositi o n at 2 0 mi n utes 
after d osi n g/i nf usi o n. Vital si g ns will be assesse d at scree ni n g visit, Da y 1 t o 6 ( pre-d ose), Da y 7 t o Da y 9 (eac h L T 3 0 0 1 d osi n g peri o d at pre-d ose, 2 0 mi n utes a n d 6 0 
mi n ut es after i nf usi o n is i nitiate d) a n d f oll o w -u p visit o n Da y 1 6 . 
g   
A 1 2 -lea d E C G assess me nt will be perf or me d at scree ni n g visit a n d at pre-d ose a n d 1 h o ur after ta ki n g cl o pi d o grel o n Da y 2 t o Da y 6 , a n d after 1 h o ur after t he i nf usi o n 
is i nitiate d of t he first d ose of L T 3 0 0 1 o n Da y 7 t o Da y 9  a n d f oll o w -u p visit o n Da y 1 6 . 
h   
P K bl o o d sa m ples of L T 3 0 0 1 will be 
 
 
 
. 
i   
P K bl o o d sa m ples of L T 3 0 0 1 will be c ollecte d o n  
  
 
 
  
   
 
 
 
  
j   
P K bl o o d sa m ples of cl o pi d o grel will be 
 
 
 
k. 
Platelet f u ncti o n test a n d c oa g ulati o n test will be meas ure d
 
 
l. 
Platelet f u ncti o n test a n d c oa g ulati o n test  will be meas ure d o n t he first d ose of L T 3 0 0 1 o n Da y 7 at 1 5 mi n after i nf usi o n is  i nitiate d (e n d of i nf usi o n) 
m.  
Platelet f u ncti o n test a n d c oa g ulati o n test  will be meas ure d o n t he last d ose of L T 3 0 0 1 o n Da y 9 at 1 5 mi n after i nf usi o n is i nitiate d (e n d of i nf usi o n)  
n   
C oa g ulati o n para meters will i ncl u de P T, I N R, a P T T a n d T T . 
o   
He mat ol o g y tests  will i ncl u de H b, R B C, M C V, Hct, M C H, W B C, W B C -D C, a n d platelets.  
p   
Cli nical c he mistr y tests will i ncl u de B U N, creati ni ne, fasti n g bl o o d gl uc ose, A L P, A L T, A S T, G G T, t otal bilir u bi n, t otal pr ot ei ns, al b u mi n/ gl o b uli n rati o, Na, K, Cl, Ca, 
bicar b o nate, uric ac i d, C K, c h olester ol, tri gl yceri des, free ir o n, a n d ferriti n. 
q   
Uri nal ysis will i ncl u de di pstic k uri nal ysis a n d micr osc o pic e xa mi nati o n.  
r   
W he n t he uri ne dr u g/ c oti ni ne /alc o h ol tests a n d/ or cli nical la b orat or y tests i ncl u di n g c oa g ulati o n, he mat ol o g y a n d cli nical c he mistr y are perf or me d o n Da y -4 t o Da y -2 , 
t hese tests nee d n ot be re peate d o n Da y -1.  
s   
I n t he e ve nt of earl y ter mi nati o n ( E T), a ra n d o mize d s u bject will c o m plete t he E T pr oce d ures. T he c ollecti o n of P K bl o o d sa m ples of L T 3 0 0 1 a n d/ or cl o pi d o grel ca n be 
e xe m pte d base d o n t he I n vesti gat or’s discreti o n if t he s u bject di d n ot recei ve t he i n dicate d st u d y dr u g. 
t   
A si n gle d ose of L T 3 0 0 1 dr u g pr o d uct will be gi ve n o n Da y 1 .  

C O N FI D E N TI A L  
 
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 3 0  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
u   
A 3 0 -mi n ute wi n d o w is all o we d f or n o n -P K pr oce d ures . 

C O N FI D E N TI A L  
 
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 3 2  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
Pri or a n d c o nc o mita nt me dicati o n   
X   
X  
X  
A d verse e ve nt  
X   
X  
X  
E C G = electr ocar di o gra m; E T = earl y ter mi nati o n; P K = p har mac o ki netic  
a   
Vir ol o g y tests will i ncl u de HI V a nti b o d y, H Bs A g, he patitis C vir us a nti b o d y, a n d C O VI D -1 9  a nti b o d y. 
b   
De m o gra p hics will i ncl u de  a ge, ge n der, hei g ht, b o d y wei g ht, B MI a n d race. O n Da y -1 , o nl y b o d y wei g ht will be meas ure d.  
c   
Ser u m pre g na nc y test will be perf or me d i n fe male s u bjects of c hil d beari n g p ote ntial  wit hi n 2 4 h o urs pri or t o t he first dr u g treat me nt o n Da y 1.  
d   
T he first d ose of a pi xa ba n o n Da y 5 , Da y 6 a n d Da y 7 will be f oll o we d i m me diatel y b y
 L T 3 0 0 1 a d mi nistere d as a 1 5 -mi n ute I V i nf usi o n  
e   
P h ysical e xa mi nati o n will be perf or me d at scree ni n g visit, pre -d ose o n Da y 1, t he e n d of a pi xa ba n si n gle treat me nt o n Da y 4 , t he e n d of c o m bi nati o n treat me nt o n Da y 
7  a n d f oll o w -u p visit o n Da y 1 4 . 
f   
Vital si g ns will i ncl u de b o d y te m perat ure, bl o o d press ure, res pirat or y rate, a n d heart rate. Meas ure me nts will be ma de after t he s u bject has reste d i n a s u pi ne p ositi o n 
f or at least 3 mi n utes. Bl o o d press ure will be assesse d i n seate d a n d s u pi ne p ositi o n at pre d ose a n d 6 0 mi n utes a fter d osi n g/i nf usi o n, o nl y s u pi ne p ositi o n at 2 0 mi n utes 
after d osi n g/i nf usi o n. Vital si g ns will be assesse d at scree ni n g visit, Da y 1 t o 4 ( pre-d ose), Da y 5 t o Da y 7 (eac h L T 3 0 0 1 d osi n g peri o d at pre-d ose, 2 0 mi n utes a n d 6 0 
mi n utes  after i nf usi o n is i nitiate d) a n d f oll o w -u p visit o n Da y 1 4 . 
g   
A 1 2 -lea d E C G assess me nt will be 
 
. 
h   
P K bl o o d sa m ples of L T 3 0 0 1 will be c ollecte d
 
. 
i   
P K bl o o d sa m ples of L T 3 0 0 1 will be c ollecte d 
   
 
  
   
 
 
 
).  
j   
P K bl o o d sa m ples of a pi xa ba n will be 
 
 
. 
k. 
Platelet f u ncti o n test a n d c oa g ulati o n test will be 
  
 
 
l. 
Platelet f u ncti o n test a n d c oa g ulati o n test  will be meas ure d o n t he first d ose of L T 3 0 0 1 at 1 5 mi n after i nf usi o n is i nitiate d (e n d of i nf usi o n) o n Da y 5  
m.  
Platelet f u ncti o n test a n d c oa g ulati o n test  will be meas ure d o n t he last d ose of L T 3 0 0 1 at 1 5 mi n after i nf usi o n is i nitiate d (e n d of i nf usi o n) o n Da y 7  
n   
C oa g ulati o n para meters will i ncl u de P T, I N R, a P T T a n d T T . 
o   
He mat ol o g y tests will i ncl u de H b, R B C, M C V, Hct, M C H, W B C, W B C -D C, a n d platelets.  
p   
Cli nical c he mistr y tests will i ncl u de B U N, creati ni ne, fasti n g bl o o d gl uc ose, A L P, A L T, A S T, G G T, t otal bili r u bi n, t otal pr otei ns, al b u mi n/ gl o b uli n rati o, Na, K, Cl, Ca, 
bicar b o nate, uric aci d, C K, c h olester ol, tri gl yceri des, free ir o n, a n d ferriti n.  
q   
Uri nal ysis will i ncl u de di pstic k uri nal ysis a n d micr osc o pic e xa mi nati o n.  
r   
W he n t he uri ne dr u g/ c oti ni ne /alc o h ol tests a n d/ or cli nical la b orat or y tests i ncl u di n g c oa g ulati o n, he mat ol o g y a n d cli nical c he mistr y are perf or me d o n Da y -4 t o Da y -2 , 
t hese tests nee d n ot be re peate d o n Da y -1.  
s   
I n t he e ve nt of earl y ter mi nati o n ( E T), a ra n d o mize d s u bject will c o m plete t he E T pr oce d ures. T he c ollecti o n of P K bl o o d sa m p les of L T 3 0 0 1 a n d/ or a pi xa ba n ca n be 

C O N FI D E N TI A L  
 
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 3 3  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
e xe m pte d base d o n t he I n vesti gat or’s discreti o n if t he s u bject di d n ot recei ve t he i n dicate d st u d y dr u g.  
t. 
A si n gle d ose of L T 3 0 0 1 dr u g pr o d uct will be gi ve n o n Da y 1  
u. 
A 3 0 -mi n utes wi n d o w is all o we d f or n o n -P K pr oce d ures.  

C O N FI D E N TI A L  
 
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 3 5  of 8 8  
 
Stat us: V 1. 4, Date 1 1 Mar 2 0 2 1  
a   
Vir ol o g y tests will i ncl u de HI V a nti b o d y, H Bs A g, he patitis C vir us a nti b o d y , a n d C O VI D -1 9  a nti b o d y. 
b   
De m o gra p hics will i ncl u de  a ge, ge n der, hei g ht, b o d y wei g ht, B MI a n d race. O n Da y -1 , o nl y b o d y wei g ht will be meas ure d.  
c   
Ser u m pre g na nc y test will be perf or me d i n fe male s u bjects of c hil d beari n g p ote ntial  wit hi n 2 4 h o urs pri or t o t he first dr u g treat me nt o n Da y 1.  
d   
T he first d ose of da bi gatra n o n Da y 5 , Da y 6 a n d Da y 7 will be f oll o we d i m me diatel y b y 
 L T 3 0 0 1 a d mi nistere d as a 1 5-mi n ute I V i nf usi o n  
e   
P h ysical e xa mi nati o n will be perf or me d at scree ni n g visit, pre -d ose o n Da y 1, t he e n d of da bi gatra n si n gle treat me nt o n Da y 4 , t he e n d of c o m bi nati o n treat me nt o n Da y 
7 a n d f oll o w -u p v isit o n Da y 1 4 . 
f   
Vital si g ns will i ncl u de b o d y te m perat ure, bl o o d press ure, res pirat or y rate, a n d heart rate. Meas ure me nts will be ma de after t he s u bject has reste d i n a s u pi ne p ositi o n 
f or at least 3 mi n utes. Bl o o d press ure will be assesse d i n seate d a n d s u pi ne p ositi o n a t pre d ose a n d 6 0 mi n utes after d osi n g/i nf usi o n, o nl y s u pi ne p ositi o n at 2 0 mi n utes 
after d osi n g/i nf usi o n. Vital si g ns will be assesse d at scree ni n g visit, Da y 1 t o 4 ( pre-d ose), Da y 5 t o Da y 7 (eac h L T 3 0 0 1 d osi n g peri o d at pre-d ose, 2 0 mi n utes a n d 6 0 
mi n ut es after i nf usi o n is i nitiate d) a n d f oll o w -u p visit o n Da y 1 4 . 
g   
A 1 2 -lea d E C G assess me nt will be perf or me d at scree ni n g visit 
 
 
h   
P K bl o o d sa m ples of L T 3 0 0 1 will be 
 
 
i   
P K bl o o d sa m ples of L T 3 0 0 1 will be 
   
 
  
   
 
 
 
  
j   
P K bl o o d sa m ples of da bi gatra n will be c ollecte d 
 
 
. 
k. 
Platelet f u ncti o n test a n d c oa g ulati o n test will be 
  
 
 
l. 
Platelet f u ncti o n test a n d c oa g ulati o n test  will be meas ure d o n t he first d ose of L T 3 0 0 1 at 1 5 mi n after i nf usi o n is i nitiate d (e n d of i nf usi o n) o n Da y 5  
m.  
Platelet f u ncti o n test a n d c oa g ulati o n test  will be meas ure d o n t he last d ose of L T 3 0 0 1 at 1 5 mi n after i nf usi o n is i nitiate d (e n d of i nf usi o n) o n Da y 7  
n   
C oa g ulati o n para meters will i ncl u de P T, I N R, a P T T a n d T T . 
o   
He mat ol o g y tests will i ncl u de H b, R B C, M C V, Hct, M C H, W B C, W B C -D C, a n d platelets.  
p   
Cli nical c he mistr y tests will i ncl u de B U N, creati ni ne, fasti n g bl o o d gl uc ose, A L P, A L T, A S T, G G T, t otal bili r u bi n, t otal pr otei ns, al b u mi n/ gl o b uli n rati o, Na, K, Cl, Ca, 
bicar b o nate, uric aci d, C K, c h olester ol, tri gl yceri des, free ir o n, a n d ferriti n.  
q   
Uri nal ysis will i ncl u de di pstic k uri nal ysis a n d micr osc o pic e xa mi nati o n.  
r   
W he n t he uri ne dr u g/ c oti ni ne /alc o h ol tests a n d/ or cli nical la b orat or y tests i ncl u di n g c oa g ulati o n, he mat ol o g y a n d cli nical c he mistr y are perf or me d o n Da y -4 t o Da y -2 , 
t hese tests nee d n ot be re peate d o n Da y -1.  
s   
I n t he e ve nt of earl y ter mi nati o n ( E T), a ra n d o mize d s u bject will c o m plete t he E T pr oce d ures. T he c ollecti o n of P K bl o o d sa m p les of L T 3 0 0 1 a n d/ or da bi gatra n ca n be 
e xe m pte d base d o n t he I n vesti gat or’s discreti o n if t he s u bject di d n ot recei ve t he i n dicate d st u d y dr u g. 
t   
A si n gle d ose of L T 3 0 0 1 dr u g pr o d uct will be gi ve n o n Da y 1 . 
u. 
A 3 0 -mi n ute wi n d o w is all o we d f or n o n -P K pr oce d ures . 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 3 6  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
3.   
I ntr o d ucti o n 
3. 1.   
St u d y R ati o n ale  
T his P hase  1 st u d y ( L T 3 0 0 1 -1 0 5) is pla n ne d t o esta blis h t he cli nical safet y a n d p har mac o ki n etics ( P K) 
pr ofile of m ulti ple d ose of L T 3 0 0 1 dr u g pr o d uct 
 a n d t o i n vesti gate dr u g i nteracti o ns of 
L T 3 0 0 1 wit h p ote ntial c o nc o mita nt me dicati o ns i n heal t h y s u bjects. 
3. 2.   
B ac k gr o u n d  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
L T 3 0 0 1 is a n o vel s mall m olec ule wit h b ot h cere bral bl o o d fl o w rest orati o n a n d free ra dical -
sca ve n gi n g acti vities as s h o w n i n n o ncli nical st u dies a n d t h us ca n p ote ntiall y be a ne w t hera p y f or 
treati n g ac ute isc h e mic str o ke.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 3 7  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
A P hase 1 si n gle I V i nf usi o n of L T 3 0 0 1 dr u g pr o d uct i n healt h v ol u nteer st u d y ( L T 3 0 0 1 -1 0 1) has bee n 
c o m plete d at a cli nical site i n t he U nite d States, w hic h i n dicate t hat t he L T 3 0 0 1 dr u g pr o d uct is safe 
a n d well t olerate d at all d oses teste d (si n gle d ose of 
 gi ve n as a 1 5 mi n ute 
I V i nf usi o n). 
T he safet y  of L T 3 0 0 1 wit h c o nc o mita nt dr u gs c o m m o nl y use d b y ac ute isc he mic str o ke patie nts is 
t heref ore of great i nterest. A nti platelet a ge nts, s uc h as as piri n a n d cl o pi d o grel, are use d f or b ot h t he 
ma na ge me nt of ac ute is c he mic str o ke a n d t h e pre v e nti o n of str o ke. A ntic oa g ula nts i ncl u di n g a pi xa ba n 
a n d da bi gatra n are c o m m o nl y use d f or str o ke pre v e nti o n i n atrial fi brillati o n patie nts.  
3. 2. 1.   
N o ncli nic al St u dies  
L T 3 0 0 1 is a n o vel s mall m olec ule desi g ne d t o ha ve b ot h t hr o m b ol ytic a n d free ra di cal -sca ve n gi n g 
acti vities, w hic h were c h aract erize d i n vari o us i n vitr o a n d i n vi v o m o dels. I n vitr o st u dies ha v e s h o w n 
t hat L T 3 0 0 1 e x hi bite d s u bsta ntial a nti o xi dati o n acti vity. I n a ni mal st u dies L T 3 0 0 1 ca n rest ore bl o o d 
fl o w, re d uce cere bral i nf arct v ol u me, a n d i m pr o ve ne ur ol o gical o utc o me i n r o de nt a n d n o n h u ma n 
pri mate str o ke m o dels, wit h a n a p pare nt wi d er t hera pe utic ti me wi n d o w a n d a better safet y pr ofile t h a n 
t h ose re p ort ed f or rt P A. T he e ffect of L T 3 0 0 1 o n t he blee di n g ti me was e val uate d i n mal e I C R mice 
a n d was c o m para bl e t o a ni mals t hat recei v e d ve hicl e c o ntr ol a n d si g nifica ntl y s h orter t ha n t h ose treat e d 
wit h rt P A ( 1 0 m g/ k g).  
 
  
 
  
 
 
 
   
 
  
 
 
 
 
 
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 3 8  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
 
 
 
 
 
 
 
 
 
 
   
 
 
 
  
 
 
 
 
  
 
 
   
 
 
 
 
 
 
 
 
 
 
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 4 0  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. 2. 3.   
S afet y  
Cli nical e vi de nce i n healt h y s u bjects i n dicate t hat t he L T 3 0 0 1 dr u g pr o d uct is safe a n d well-t olerate d 
at t he d oses teste d (ie, si n gle d oses of 
 gi ve n as a 1 5-mi n ute I V i nf usi o n).  
3. 3.   
Be nefit/ Ris k Assess me nt  
T he d ose select e d f or t his m ulti ple -d ose st u d y ha d bee n pre vi o usl y e val u ate d i n a si n gle d ose st u d y. 
T here were n o cli nicall y si g nifica nt c ha n g es i n s afet y para met ers.  N o cli nical efficac y st u dies ha ve 
bee n c o m plete d  wit h L T 3 0 0 1 Dr u g Pr o d uct, s o a direct be n efit -ris k ass ess me nt has n ot bee n perf or me d. 
M ore det aile d i nf or m ati o n a b o ut t he k n o w n a n d e x pecte d b e nefits a n d ris ks a n d reas o n a bl y e x p ecte d  
a d verse e ve nts of L T 3 0 0 1  ma y be f o u n d i n t he I n vesti gat or’s Br oc h ure. 
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 4 2  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
5.   
St u d y Desi g n  
5. 1.   
O ver all  Desi g n  
T his st u d y is a t w o -part st u d y  (Fi g ure 1 ). Part A is d o u ble-bli n d, place b o -c o ntr olle d, a n d will e xa mi ne 
t he safet y a n d P K pr ofil es of m ulti ple d oses of L T 3 0 0 1 dr u g pr o d uct i n healt h y s u bjects. Part B is 
o pe n -la bel a n d will assess t he safet y a n d P K of L T 3 0 0 1 w he n c o a d mi nistere d  wit h as piri n, cl o pi d o grel, 
a pi xa ba n or da bi gatra n.  
 
After pr o visi o n of writte n i nf or me d c o nse nt, eac h s u bject will be e v al uate d f or st u d y eli gi bilit y d uri n g 
t he scree ni n g peri o d, w hi c h is wit hi n  3 0 da ys pri or t o recei vin g t he st u d y dr u g ( Da y 1). 
P art A  
Eli gi ble s u bjects  will be a d mitte d t o t he site o n Da y -1 a n d u n d er g o a d diti o nal eli gi bilit y assess me nts. 
T h ose rec o nfir me d as eli gi ble will  be ra n d o ml y assi g ne d t o st u d y treat me nt. A p pr o xi matel y 1 6  h ealt h y 
s u bjects will be ra n d o mi ze d i n a3: 1 rati o t o recei ve eit her L T 3 0 0 1 dr u g pr o d uct 
 or 
place b o a d mi nistere d as a 1 5 -mi n ute i ntra v e n o us (I V) i nf usi o n. Eac h s u bject will recei ve t hree d os es, 
a d mi nistere d 3 h o urs a p art, o n Da ys 1, 2, a n d 3. S u bjects will be release d fr o m t he site o n Da y 4 
f oll o wi n g all safet y a n d P K pr oce d ures. 
T he first 4 s u bjects will be “se nti nel s u bjects,” wit h 2  s u bjects assi g ne d t o recei ve L T 3 0 0 1 dr u g pr o d uct 
a n d t he ot h er  2  s u bjects assi g ne d t o recei ve  place b o . T he I n vesti gat or will revie w all a v aila ble s afet y 
data fr o m t he se nti nel s u bjects. If c o nsi dere d safe t o d o s o, t he re mai ni n g s u bjects will be d ose d.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 4 7  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
6.   
St u d y P o p ul ati o n  
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o k n o w n as 
pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d.  
6. 1.   
I ncl usi o n Criteri a 
Partici pa nts are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y:  
1.  Si g ne d t he i nf or me d c o nse nt f or m (I C F) as descri be d i n A p pe n di x 3  w hic h i ncl u des c o m plia nce 
wit h t he re q uire me nts a n d restricti o ns liste d i n t he I C F (I C F) a n d i n t his pr ot oc ol 
2.  S u bject is a male or fe m ale bet wee n 1 8 a n d 6 5  years of a ge o n t h e da y of scree ni n g.  
3.  S u bject’s b o d y wei g ht is ≥5 0  k g a n d b o d y mass i n de x is  wit hi n t he ra n ge of 1 8 t o 3 2  k g/ m 2 
(i ncl usi ve). 
4.  S u bject is a healt h y v ol u nteer c o nfir me d b y a c o m pre he nsi ve cli nical ass ess me nt, i ncl u di n g 
detaile d me dical hist or y, a c o m plete p h ysi cal e x a mi nati o n, fasti n g bl o o d gl uc ose, vital si g n 
meas ure me nts, E C G res ul ts, a n d la b orat or y i n vesti gati o ns ( he mat ol o g y, cli nical c he mistr y, a n d 
uri nal ysis). T he res ults s h o ul d be cli nicall y acce pta ble f or healt h y s u bjects per t he pri nci ple 
I n v esti gat or’s ass ess me nt. 
5.  S u bject’s P T , a P T T, a n d T T are wit hi n t he n or m al la b orat or y ra n ge.  
6.  Fe male s u bject m ust be of n o n -c hil d beari n g p ote ntial or , if of c hil d-beari n g p ote ntial, m ust be 
usi n g me dicall y acce pt a ble c o ntrace pti ve meas ures (A p pe n di x 5 ) t hr o u g h o ut t he d urati o n of 
t he st u d y a n d f or at least 3 0 da ys after recei vi n g t h e last d ose of st u d y treat me nt. A w o ma n of 
n o nc hil d beari n g p ote ntial is defi ne d as a w o ma n w h o is o ver 5 5 y ears ol d a n d p ost me n o pa usal 
at least 1 2 m o nt hs pri or t o scree ni n g or a w o ma n w h o is s ur gicall y sterile.  
7.  Male s u bjects a n d t heir p ar t ners of c hil d beari n g p ote ntial m ust c o m mit t o t he use of me dicall y 
acce pta ble c o ntrace pti o n  (A p pe n di x 5 ) f or t he st u d y d urati o n. M e n m ust refrai n fr o m d o nati n g 
s per m d uri n g t his sa me peri o d. T he fe mal e part ners s h o ul d be as ked t o use a c o ntrace pti o n 
met h o d t hat is me dicall y acce pta ble, a n d t hese c o ntrace pti ve meas ures s h o ul d be use d 
t hr o u g h o ut t he d urati o n of t he st u d y a n d f or at least 3 0 da ys after t heir last d ose of st u d y 
treat me nt. 
8.  S u bject is a n o ns m o ker (a bsti ne nce f or at least 6 m o nt hs pri or t o scree ni n g).  
9.  A C hi nese s u bject is defi ne d as a first -ge nerati o n C hi nese ( b ot h pare nts of C hi nese desce nt) 
w h o mai ntai ns a t y pical C hi nese lifest yle, i ncl u di n g diet. I n a d diti o n t o mai nla n d C hi na, 
s u bjects or t heir pare nts ma y als o be fr o m T ai wa n, H o n g K o n g, or M o n g olia. 
N ote: Retesti n g of a b n or mal la b val ues t hat ma y l ea d t o e xcl usi o n will be all o we d o nce. Retesti n g 
will ta ke place d uri n g a n u nsc he d ule d visit i n t he scree ni n g p h ase.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 4 8  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
6. 2.   
E xcl usi o n Criteri a   
Partici pa nts are e xcl u de d fr o m t he st u d y if a n y of t he f oll o wi n g criteria a p pl y:  
1.  S u bject has a p ositi ve res ult fr o m a n alc o h ol or dr u g test f or a m p heta mi nes, bar bit urates, 
c ocai ne, o pi ates, ca n n a bi n oi ds, or be nz o diaze pi nes d uri n g scree ni n g.  
2.  S u bject has a p ositi ve res ult fr o m a he patitis B vir us ( H B V) test ( he p atitis B s urface a nti ge n; 
H Bs A g) or he patitis C vir us ( H C V) test (a nti -H C V a nti b o d y) wit hi n 3 m o nt hs of scree ni n g.  
3.  S u bject has a hist or y of HI V i nfecti o n.  
4.  S u bject has a c urre nt or rece nt hist or y ( wit hi n 6 m o nt hs pri or t o s cree ni n g) o f re g ul ar alc o h ol 
c o ns u m pti o n ( ie, at least 2 o u nces of al c o h ol or 2 dri n ks per da y).  
5.  S u bject has recei ve d a n y i n vesti gati o nal pr o d uct wit hi n 3 0 da ys or 5 half -li ves ( w hic he ver is 
l o n ger) pri or t o t he first d osi n g da y or is pla n ni n g t o partici pate i n a cli nical trial d uri n g t he 
st u d y peri o d.  
6.  S u bject has use d pres cri pti o n or n o n pres cri pti o n dr u gs, i ncl u di n g vita mi ns, her bal a n d dietar y 
s u p ple me nts wit hi n 7 da ys pri or t o t he first d ose of st u d y dr u g, u nless t he me dicati o n will n ot 
i nterfere wit h t h e st u d y pr oce d ures or c o m pr o mise s u bject safet y i n t he o pi ni o n of t he 
I n v esti gat or. 
7.  S u bject has a hist or y of s e nsiti vit y t o a n y of t h e st u d y dr u gs or c o m p o ne nts t here of, or a hist or y 
of dr u g or ot her aller g y t hat, i n t he o pi ni o n of t he I n v esti gat or, c o ntrai n dicates partici pati o n.  
8.  S u bject has d o nate d bl o o d or bl o o d pr o d ucts wit hi n 5 6 da ys pri or t o scree ni n g.  
9.  Fe male s u bj ect of c hil d beari n g p ote ntial has a p ositi ve res ult f or ser u m pre g na nc y test o n Da y 
-1.  
1 0.  Male s u bject is pla n ni n g a pre g na n c y wit h a fe mal e part ner fr o m scree ni n g u ntil 3 0 da ys after 
c o m pleti n g st u d y dr u g treat me nt.  
1 1.  S u bject is u n willi n g or u na ble t o f oll o w t h e pr oce d ures o utli ne d i n t he pr ot oc ol i n t he o pi ni o n 
of t he I n vesti gat or. 
1 2.  S u bject has a pres e nce or hist or y of c oa g ulati o n a b n or malit y.  
1 3.  S u bject has a b n or mal la b orat or y val ues or cli nical fi n di n gs o n scree ni n g t hat are j u d ge d 
cli nicall y si g nifica nt b y t he I n vesti gat or. 
1 4.  S u bject has a hist or y of cli nicall y si g nifica nt re nal or li ver d ysf u ncti o n.  
1 5.  S u bject has a pres e nce or hist or y of ps yc hiatric ill ness or me ntal i m pair me nt. 
1 6.  S u bject has a si g nifica nt ris k f or s uici dal be ha vi or i n t he o pi ni o n of t he I n v esti gat or. 
1 7.  S u bject has a hist or y of l o n g Q T s y n dr o me ( pers o nal or fa mil y) or car diac c o n d ucti o n dis or der, 
or cli nicall y si g nifica nt car diac disease.  
1 8.  Uri nar y c oti ni ne le v els at scree ni n g are i n dicati ve of s m o ki n g or s u bject has hist or y of re g ular 
use of t o bacc o - or nic oti n e -c o ntai ni n g pr o d ucts pri or t o scree ni n g.  
1 9.  S u bject is a n e m pl o yee ( per ma ne nt, te m p orar y c o ntract w or ker, or desi g nee res p o nsi ble f or  t he 
c o n d uct of t he st u d y) of t he I n vesti gat or or st u d y site, or i m me diate fa mil y * of s uc h e m pl o yees 
or t he I n vesti gat or. 
2 0.  S u bject is a n e m pl o yee or i m me diate fa mil y * of a n e m pl o yee of L u m osa T hera pe utics C o., Lt d. 
or c o ntract researc h or ga nizati o n c o n d ucti n g t he trial.   
(*I m me diate fa mil y is d efi ne d as a s p o use, p are nt, c hil d, or si bli n g, w het her bi ol o gical or 
le gall y a d o pte d.) 
2 1.  S u bject has a n acti ve i nfecti o n of c or o na vir us disease 2 0 1 9 at scree ni n g.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 4 9  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
2 2.  S u bjects w h o are e nr olle d i n Part B a n d aller gic t o acet ylsalic ylic aci d, ot her salic ylat es, 
cl o pi d o grel, t hie n o p yri di nes (e g , ticl o pi di ne, pras u grel), a pi xa ba n or da bi g atra n.  
2 3.  S u bjects w h o are e nr olle d i n Part B a n d ta ki n g me dicati o ns t hat affect t he P K c haract eristics 
of as piri n, cl o pi d o gr el, a pi xa ba n or da bi gatra n.  
2 4.  S u bjects nee d t o recei ve a s ur ger y or cli nical pr oce d ures ass o ciate d wit h hi g h blee di n g ris k.  
2 5.  Part B C o h ort 2 o nl y: s u bjects w h o are p o or m eta b olizers of cl o pi d o grel ( C Y P 2 C 1 9 * 2/ * 2, 
* 2/ * 3, or * 3/ * 3 ge n ot y pe)  
2 6.  S u bject has a hist or y  of mi n or blee di n g e pis o d es, e g, e pista xis, rectal blee di n g, gi n gi val 
blee di n g.  
2 7.  S u bject has  a hist or y of pe ptic ulcer or gastr oi ntesti nal blee di n g.  
6. 3.   
Lifest yle Restricti o ns  
6. 3. 1.   
Me als a n d Diet ar y Restricti o ns  
1.  Refrai n fr o m c o ns u m pti o n of re d wi ne, Se ville ora n ge s, gra pefr uit or gra pefr uit j uice, 
p o mel os, e x otic citr us fr uits, gra pefr uit h y bri ds , or fr uit j uices fr o m 3  da ys b ef ore t h e start of 
st u d y treat me nt u ntil after t he fi nal d ose . 
6. 3. 2.   
C affei ne, Alc o h ol, a n d T o b acc o  
1.  S u bjects  will a bstai n fr o m i n gesti n g caffei ne - or xa nt hi ne -c o ntai ni n g pr o d ucts ( e g, c offee, 
tea, c ola dri n ks, a n d c h oc olate) f or 2 4  h o urs bef ore  c ollecti o n of a n y P K sa m ple u ntil after 
c ollecti o n o f t he fi nal P K  sa m ple. 
2.  S u bjects will a bstai n fr o m alc o h ol f or 2 4 h o urs b ef ore  t h e first d ose u ntil after c ollecti o n o f 
t he fi nal P K  sa m ple.  
3.  Use of t o bacc o pr o d u cts will n ot  be  all o we d d uri n g t he st u d y . 
6. 3. 3.   
Acti vit y  
1.  S u bjects will a bstai n fr o m stre n u o us e xercise f or 2 4  h o urs bef ore eac h bl o o d  c ollecti o n f or 
cli nical la b orat or y tests.  S u bjects  ma y partici pate i n li g ht recreati o nal acti vities d uri n g st u dies 
(e g, watc h i n g tel e visi o n, rea di n g). 
6. 4.   
Scree n F ail ures  
Scree n fail ures are defi n e d as partici pa nt s w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut are n ot 
s u bse q ue ntl y ra n d o ml y assi g ne d t o st u d y treat me nt or e ntere d i n t he st u d y . A mi ni mal set of scree n 
fail ure i nf or mati o n is re q uire d t o e ns ure tra ns pare nt re p orti n g of scree n fail ure partici pa nt s t o meet t he 
C o ns oli date d Sta n dar ds of Re p orti n g Trials ( C O N S O R T) p u blis hi n g re q uire me nts a n d t o res p o n d t o 
q ueries fr o m re g ul at or y a ut h orities. Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, scree n fail ure d etails, 
eli gi bilit y criteria, a n d a n y S A E . 
I n di vi d uals w h o d o n ot meet t he criteri a f or p arti ci pati o n i n t his st u d y (scree n fail ure) ma y n ot  be 
rescree ne d. 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5 1  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
T he d ose le vel of L T 3 0 0 1  dr u g pr o d uct will be calc ulate d b y t he I n vesti gat or or a q ualifie d desi g nee 
base d o n t he s u bject’s b o d y wei g ht a n d c o nfir me d b y t he u n bli n de d p har macist bef ore st u d y treat me nt 
pre parati o n.  
L T 3 0 0 1 dr u g pr o d uct a n d place b o s h o ul d be rec o nstit ute d pri or t o u se wit h n or mal sali ne ( 0. 9 % 
S o di u m C hl ori de) t o a fi n al c o nce ntrati o n of 4  m g/ m L. L T 3 0 0 1 dr u g pr o d uct will be f urt h er dil ute d t o 
a s uita ble c o nce ntrati o n wit h n or mal sali ne a n d a d mi nistere d via a 1 5 -mi n ute I V i nf usi o n. I nstr ucti o ns 
f or rec o nstit uti o n a n d dil uti o n will be pr o vi de d se paratel y t o t he sites. 
T he rec o nstit ute d L T 3 0 0 1 dr u g pr o d uct a n d place b o s ol uti o n c o ul d be st ore d at r o o m te m perat ure f or 
8 h o urs or at 2° C t o 8° C ( 3 5. 6° F t o 4 6. 4° F) f or 2 4 h o urs.   
 
Dr u g s u p plies of L T 3 0 0 1 dr u g pr o d uct a n d place b o will be pr o vi de d b y t he S p o ns or.  
7. 3.   
D ose M o dific ati o n  
N o c ha n ges t o d oses or d osi n g sc he d ule are all o we d.  
7. 4.   
Met h o d of Tre at me nt Assi g n me nt  
I n Part A, t he first f o ur se nti nel s u bjects will be ra n d o ml y assi g ne d t o L T 3 0 0 1 dr u g pr o d uct or place b o 
i n a 1 : 1 rati o. T he re m ai ni n g s u bjects will be ra n d o mize d i n a 3: 1 rati o.  
I n Part B, s u bjects will be se q ue ntiall y assi g ne d t o o ne of f o ur treat me nt c o h orts.  
7. 5.   
R a n d o miz ati o n Pr oce d ures  
I n Part A, i n or der t o preser ve t he bli n di n g of t he s u bject or t he pers o n nel i n v ol ve d i n s u bject 
e val uati o ns or d ata c ollecti o n, a n u n bli n de d p h ar macist w h o is n ot directl y i n v ol ve d i n t he st u d y 
c o n d uct, dat a ma na ge me nt, or dat a a nal ysis will be desi g nat e d. T he I n v esti gat or or d esi g nee s h o ul d 
pr o vi de t he necessar y i n f or mati o n t o t he u n bli n de d p har macist w h o will o btai n t he assi g n me nt of t he 
s u bject’s treat me nt acc or di n g t o t he ra n d o mizati o n c o de list. Neit her t h e s u bject n or t h e I n v esti gat or 
will k n o w t he treat me nt t o w hic h t he s u bject has bee n assi g ne d.  
7. 6.   
M ai nte n a nce o f R a n d o miz ati o n C o des 
I n Part A, ra n d o mizati o n c o des will be pr o vi de d t o t he u n bli n de d p har macist w h o pre pares st u d y 
treat me nts a n d t he u n bli n de d bi ostatisticia n(s) perf or m t he P K a nal ysis at t h e be gi n ni n g  of Part A.  T he 
p har macist will use t he ra n d o mizati o n c o de list f or treat me nt assi g n me nt a n d pre pari n g s u bject d oses 
t hr o u g h o ut t he st u d y. 
7. 7.   
Bli n di n g  
Part A is d o u ble -bli n d.  T he u n bli n de d p har macist at t he st u d y site will pre p are t h e st u d y dr u g. I n or der 
t o pr otect t he bli n di n g of t he s u bjects a n d I n v esti gat ors, t he I V ba g will be mas ke d pr o perl y. Beca us e 
of t he d o u ble -bli n d desi g n of Part A, t he I n vesti gat or or desi g nee s h o ul d treat a n d e val uate all s u bjects 
as t h o u g h t he y recei ve d L T 3 0 0 1 dr u g pr o d uct . O nl y t he p har macist res p o nsi ble f or treat me nt 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5 2  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
assi g n me nt  a n d t he bi ostatisticia n s ge nerati n g t he ra n d o mizati o n c o de  or perf or mi n g t he u n bli n de d P K 
a nal yses  wil l be u n bli n de d a n d will ha ve access t o treat me nt assi g n me nts; all ot her parties i n v ol ve d i n 
t he st u d y will be f ull y bli n de d u ntil Part A is c o m plete d . 
F or t he safet y re vie w meeti n g of Part A, a bli n de d P K a nal ysis will be c o n d ucte d after all healt h y 
s u bjects c o m plete st u d y pr oce d ures of Part A a n d bl o o d P K data will be re vie we d i n a bli n d ma n ner  
i n t he meeti n g. 
Part B is o pe n -la bel. 
7. 8.   
Bre a ki n g t he Bli n d  
A s u bject’s treat me nt assi g n me nt will n ot be br o ke n u ntil t he e n d of Part A u nless, i n t he I n vesti gat or’s 
o pi ni o n, k n o wle d ge of tr eat me nt assi g n me nt w o ul d alter ma na g e me nt of S A Es  or n o n -seri o us A E of 
Gra de 3 or hi g her se verit y . I n t he e ve nt t hat t he bli n d nee ds t o be br o ke n beca use of a me dical 
e mer ge n c y, t he I n vesti gat or ma y be u n bli n de d t o o b tai n t he s u bject’s treat me nt assi g n me nt. Pri or t o 
u n bli n di n g a s u bject’s treat me nt assi g n me nt, t he I n vesti gat or s h o ul d ma ke e ver y eff ort t o c o ntact t he 
me dical m o nit or t o disc uss t he me dical e mer ge nc y a n d t he reas o n f or re v eali n g t he act ual treat me nt 
receiv e d b y t hat s u bject. If a s u bj ect’s tr eat me nt is u n bli n de d, L u m osa m ust be n otifie d i m me diatel y. 
T he I n vesti gat or or desi g nee m ust clearl y d oc u me nt a n y u n bli n di n g e ve nt a n d t he d oc u me ntati o n m ust 
i ncl u de t he s u bject n u m ber, t he reas o ns f or treat m e nt u n bli ndi n g, a n d t he date o n w hic h t he c o de was 
br o ke n.  
7. 9.   
Pre p ar ati o n/ H a n dli n g/ St or a ge / Acc o u nt a bilit y 
T he I n v esti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ure c o n diti o ns ha ve b ee n mai ntai ne d 
d uri n g tra nsit f or all st u d y treat me nt recei ve d a n d a n y discre p a ncies are re p orte d a n d res ol ve d bef ore  
use of t he st u d y treat me nt. 
O nl y partici pa nt s e nr olle d i n t he st u d y ma y recei v e st u d y treat me nt a n d o nl y a ut h orize d site staff ma y 
s u p pl y or a d mi nister st u d y treat me nt. All st u d y treat me nts m ust be st ore d i n a sec ure , e n vir o n me nt all y 
c o ntr olle d , a n d m o nit ore d ( ma n ual or a ut o mate d) area i n acc or da nce wit h t he la bele d st ora ge 
c o n diti o ns wit h access li mite d t o t he I n vesti gat or a n d a ut h orize d site staff . 
T he I n vesti gat or, i nstit uti o n, or t he hea d of t he m e dical i nstit uti o n ( w here a p plica ble) is res p o nsi bl e 
f or st u d y treat me nt acc o u nta bilit y, rec o nciliati o n, a n d rec or d mai nte na n ce (ie, recei pt, rec o nciliati o n, 
a n d fi nal dis p ositi o n rec or ds) . 
T he I n vesti gat or will mai ntai n acc urate rec or ds of dr u g dis p ositi o n re q uire d b y a p pl ica ble la w, 
i ncl u di n g date a n d q u alit y a d mi nistere d, a n d s u bject t o w h o m st u d y dr u g was a d mi nistere d. Reas o ns 
f or de part ure fr o m t he e x pecte d dis pe nsi n g re gi me n m ust als o be rec or de d.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5 3  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
A st u d y dr u g acc o u nta bilit y l o g will be use d t o d oc u me nt st u d y dr u g dis p ositi o n. All ite ms o n t he l o g 
are t o be c o m plete d i n f ull. T he st u d y cli nical researc h ass ociate will e ns ure t hat t he area w here t he 
st u d y dr u g acc o u nta bilit y rec or ds are t o b e mai ntai ne d is a de q uate.  
Eac h ti me t he p har m acist desi g nate d b y t he I n vesti gat or dis pe nses st u d y dr u g f or a s u bject, h e or s h e 
is t o rec or d t he s u bject n u m ber a n d i nitials, ra n d o mizati o n n u m ber, date dis pe nse d, n u m ber of vials of 
st u d y dr u g dis pe nse d, a n d his or her i nitials. T he st u d y cli nical res earc h ass ociate will c o u nt all us e d 
a n d u n use d c o ntai ners of st u d y dr u g a n d re vie w st u d y dr u g acc o u nta bilit y rec or ds d uri n g r o uti ne 
m o nit ori n g visits. T he cli nical researc h ass ociate will als o nee d t o verif y d ose calc ulati o n t o c hec k 
w het her t he act ual d oses a d mi nistere d were t he sa me as t h ose i nte n de d.  
At t he c o m pleti o n of t he st u d y, t o satisf y re g ulat or y re q uire m e nts re gar di n g dr u g acc o u nt a bilit y, t he 
a m o u nt of  st u d y dr u g will be rec o n cile d a n d retai n e d o n site, t he u n use d st u d y dr u g will be arra n ge d 
f or ret ur n t o t he s p o ns or, or destr ucti o n acc or di n g t o site’s sta n dar d pr ot oc ols. 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5 4  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
7. 1 0.  
Tre at me nt C o m pli a nce  
L T 3 0 0 1 dr u g pr o d uct will be a d mi nistere d via a n I V i nf usi o n b y t he I n vesti gat or or q ualifie d pers o n nel.  
As piri n, cl o pi d o grel, da bi gatra n, a n d a pi xa ba n will be orall y a d mi nistere d u n der t he direct s u per visi o n 
of t he I n vesti gat or or desi g nee. A ha n d a n d m o ut h c hec k will be d o ne t o e ns ure t hat t he me dicati o n 
was s wall o we d.  
7. 1 1.  
C o nc o mit a nt T her a p y  
A n y me dicati o n or vacci ne (i ncl u di n g o ver -t he-c o u nter or prescri pti o n me dici nes, vita mi ns , a n d/ or 
her bal s u p ple me nts) t hat t he s u bject is recei vi n g at t he ti me of e nr oll me nt  or recei v es d uri n g t he st u d y 
m ust be rec or de d al o n g wit h : 
•  R eas o n f or use  
•  D ates of a d mi nistrati o n i ncl u di n g start a n d e n d dates  
•  D osa ge i nf or m ati o n i ncl u di n g d ose a n d fre q ue nc y 
T he M e dical M o nit or s h o ul d be c o ntacte d if t h ere are a n y q u esti o ns re gar di n g c o nc o mita nt or pri or 
t hera p y. 
E xce pt as n ote bel o w, s u bjects  m ust a bstai n fr o m ta ki n g prescri pti o n or n o n pres cri pti o n dr u gs 
(i ncl u di n g vita mi ns a n d dietar y or her bal s u p ple me nts) wit hi n 7 da ys ( or 1 4 da ys if t he dr u g is a 
p ote ntial e nz y me i n d ucer) or 5 half -li ves ( w hic he v er is l o n ger) bef ore  t he start of st u d y treat me nt u ntil 
c o m pleti o n of t he f oll o w -u p visit, u nless , i n t he o pi ni o n of t he I n v esti gat or a n d sp o ns or , t he me dicati o n 
will n ot i nterfere wit h t he st u d y. I n p artic ular, a n y me dicati o n w hic h affects bl o o d press ure or 
c oa g ulati o n f u ncti o ns is pr o hi bite d.  
Aceta mi n o p he n, at d os es of   2  gra ms/ da y , is p er mitte d f or use at a n y ti me d uri n g t he st u d y. Oral 
c o ntrace pti ves a n d h or m o ne re place me nt t hera p y are als o all o we d. Ot her c o nc o mita nt me dicati o n ma y 
be c o nsi dere d o n a case -b y -case b asis b y t he I n vesti gat or i n c o ns ultati o n wit h t he Me dical M o nit or. 
7. 1 1. 1.   
Resc ue Me dici ne  
T here is n o resc ue me di cati o n f or t his st u d y.  
7. 1 2.  
Tre at me nt after t he E n d of t he St u d y  
S u bjects will n ot recei ve st u d y me dicati o n after t he e n d of t he st u d y.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5 5  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
8.   
Disc o nti n u ati o n/ Wit h dr a w al Criteri a   
8. 1.   
Disc o nti n u ati o n of St u d y Tre at me nt   
If a cli nicall y si g nifica nt A E  is i de ntifie d after e nr oll me nt, t he I n vesti gat or or Me dical M o nit or  will 
deter mi ne if t he s u bject ca n c o nti n ue i n t he st u d y  a n d if a n y c h a n ge i n s u bj ect ma na g e me nt is 
nee de d .  
I n Part A, d osi n g of a n i n di vi d ual s u bject will be disc o nti n ue d i n t he e ve nt of t he f oll o wi n g:  
•  Cli nicall y si g nifica nt c ha n ges i n c oa g ulati o n para meters, w hic h i n dicat e t hat he m orr ha g e 
mi g ht occ ur.  
•  S u bject e x perie n ces a n A E of Gra d e 3 or hi g her se verit y  
•  I n vesti gat or or desi g ne e deter mi nes t hat disc o nti n uati o n of d osi n g is i n t he best i nterest of t he 
s u bject 
I n Part B, d osi n g of a n i n di vi d ual s u bject will be disc o nti n ue d i n t he e ve nt of t he f oll o wi n g: 
•  S u bject e x perie n ces a n A E of Gra d e 3 or hi g her se verit y  
•  I n vesti gat or or desi g ne e deter mi nes t hat disc o nti n uati o n of d osi n g is i n t he best i nterest of t he 
s u bject 
Part A a n d eac h c o h ort of Part B will be ter mi nate d w he n t w o s u bjects wit hi n t he sa me c o h ort 
e x perie n ce a n y st u d y dr u g relate d S A E or n o n -seri o us A E of Gra de 3 or hi g her se verit y (at least 
p ossi b l y relate d). 
See t he Sc he d ule of Acti vitie ( S o A , Secti o n 2 ) f or data t o be c ollect e d at t h e ti me of treat me nt 
disc o nti n uati o n a n d f oll o w -u p a n d f or a n y f urt her e val uati o ns t hat nee d t o b e c o m plete d . 
8. 1. 1.   
Te m p or ar y Disc o nti n u ati o n   
If a n o n-seri o us A E w hich res ulte d i n disc o nti n uati o n res ol ves wit h o ut se q uelae, t he I n vesti gat or ma y 
all o w t he s u bject t o re -j oi n t he st u d y wit hi n t he sa me c o h ort . 
8. 1. 2.   
Rec h alle n ge  
S u bjects w h o te m p oraril y disc o nti n ue d st u d y treat me nt d ue t o a n o n -seri o us A E will be cl osel y 
m o nit ore d  d uri n g rec h alle n ge. A rec urre n ce of t h e ori gi nal A E, or a w orse ni n g of t he A E, will res ult 
i n per ma ne nt disc o nti n uati o n of t hat s u bject fr o m t he st u d y. 
8. 2.   
Wit h dr a w al fr o m t he St u d y  
T he st u d y i ncl usi o n a n d e xcl usi o n criteria f or e nr oll me nt m ust be f oll o we d e x plicitl y. If a s u bject w h o 
d oes n ot meet e nr oll me nt criteria is i na d verte ntl y e nr olle d, t hat s u bject s h all be wit h dra w n fr o m t h e 
st u d y. 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5 6  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
A s u bject m a y wit h dr a w fr o m t he st u d y at a n y ti me at his/ her o w n re q u est, or ma y be wit h dra w n at 
a n y ti me at t he discreti o n of t he I n vesti gat or f or safet y, b e ha vi oral, c o m plia nce, or a d mi nistrati ve 
reas o ns. 
A d diti o nall y, t his st u d y ma y be ter mi nate d at t he discreti o n of t he S p o ns or. T he S p o ns or ma y st o p t he 
st u d y at a n y ti me f or safet y, re g ulat or y, le gal, or ot her reas o ns ali g ne d wit h G o o d Cli nical Practice 
( G C P). 
If t he s u bject wit h dra ws c o nse nt  f or discl osure of f ut ure i nf or mati o n, t he s p o ns or ma y retai n a n d 
c o nti n ue t o use a n y data c ollecte d bef ore s u c h a wit h dra wal of c o ns e nt . 
If a s u bject wit h dra ws fr o m t he st u d y, he/s he ma y re q uest destr ucti o n of a n y sa m ples ta ke n a n d n ot 
teste d, a n d t he I n v esti gat or m ust d oc u me nt t his i n t he site st u d y rec or ds . 
See  S o A f or d ata t o b e c ollecte d at t he ti me of st u d y disc o nti n uati o n a n d f oll o w -u p a n d f or a n y f urt h er 
e val uati o ns t hat nee d t o be c o m plete d.  All t he e nr olle d s u bjects wit h dra w n fr o m t he st u d y are 
e nc o ura g e d t o c o m plete all e n d-of -st u d y ( E O S) or earl y ter mi nati o n ( E T) assess me nts. 
W he n a s u bject wit h dra ws fr o m t he st u d y, t he reas o n(s) f or wit h dra wal s hall be rec or de d b y t he 
I n v esti gat or i n t he s u bject’s s o urce d oc u me nts a n d o n t he rele va nt pa ge of t he electr o nic cas e re p ort 
f or m (e C R F). 
8. 3.   
L ost t o F oll o w U p  
A s u bject will be c o nsi dere d l ost t o f oll o w -u p if he or s he re p eate dl y fails t o ret ur n f or sc h e d ule d visits 
a n d is u na ble t o be c o ntacte d b y t he st u d y site.   
T he f oll o wi n g acti o ns m ust be ta ke n if a partici p a nt  fails t o ret ur n t o t he cli nic f or a re q uire d st u d y 
visit:  
•  T he site m ust atte m pt t o c o ntact t he s u bject a n d resc he d ule t he m isse d visit as s o o n as 
p ossi ble a n d c o u nsel t he partici pa nt  o n t he i m p orta nce of  m ai ntai ni n g t he assi g ne d visit 
sc he d ule a n d ascertai n w het her or n ot t he p artici p a nt  wis hes t o a n d/ or s h o ul d c o nti n ue i n t he 
st u d y. 
•  Bef ore a  s u bj ect is dee m e d l ost t o f oll o w u p, t he I n vesti gat or or desi g nee m ust ma ke e ver y 
eff ort t o re gai n c o ntact wit h t h e partici pa nt  ( w here p ossi ble, 3 tele p h o ne calls a n d, if 
necessar y , a certifie d lett er t o t he partici pa nt ’s last k n o w n maili n g a d dress or l ocal e q ui vale nt 
met h o ds). T hese c o nt act atte m pts s h o ul d be d oc u me nte d i n t he partici pa nt ’s me dical rec or d. 
•  S h o ul d t he  s u bject c o nti n ue t o be u nreac ha bl e, he/s he will be c o nsi dere d t o ha ve wit h dra w n 
fr o m t he st u d y wit h a pri mar y reas o n of l ost t o foll o w -u p.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5 7  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
8. 4.   
Re pl ace me nts  
If a s u bject is wit h dra w n fr o m t he treat me nt peri o d of t he st u d y f or reas o ns n ot ass ociate d wit h L T 3 0 01 
dr u g pr o d uct -relate d safet y c o nsi derati o ns, t he s u bject will be re place d wit h a n ot her s u bject assi g ne d 
t o t he sa me treat me nt wit h res pect t o L T 3 0 0 1 dr u g pr o d uct a n d place b o d oses ( Part A) or a s p ecifi c 
c o h ort ( Part B). S u bjects w h o are re place me nts will be all ocat e d t he s a me ra n d o mizati o n n u m ber wit h 
t he first di git of treat me nt n u m ber bei n g re place d b y t he n u m ber 1 (e g, if ra n d o mizati o n n u m ber 
R 0 1 0 0 1 is re place d, t he n t he re place me nt n u m ber will be R 0 1 1 0 1).  
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5 8  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
9.   
St u d y Assess me nts a n d Pr oce d ures  
St u d y pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A  (Secti o n 2 ).  T otal v ol u me of bl o o d per 
s u bject i n eac h c o h ort s u m marize d i n t he T a ble 7.  
P r ot oc ol wai vers or e xe m pti o ns are n ot all o we d. I m me diat e safet y c o ncer ns s h o ul d be disc usse d wit h 
t he sp o ns or i m me diatel y u p o n occ urre n ce or a ware ness t o d eter mi ne if t he s u bject s h o ul d c o nti n ue or 
disc o nti n ue st u d y treat me nt. A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n 
t he S o A, is esse ntial a n d re q uire d f or st u d y c o n d u ct. 
All scree ni n g e val u ati o ns m ust be c o m plete d a n d re vie we d t o c o nfir m t hat  p ote ntial partici pa nt s meet 
all eli gi bilit y criteria. T h e I n vesti gat or will mai ntai n a s cree ni n g l o g t o rec or d det ails of all s u bjects 
scree n e d a n d t o c o nfir m eli gi bilit y or rec or d reas o ns f or scree ni n g fail ure, as a p plica ble.  
Pr oce d ures c o n d uct e d as part of t he s u bject’s r o uti ne cli nical ma na g e me nt (e g, bl o o d co u nt) a n d 
o btai ne d bef ore si g ni n g of t he I C F ma y b e utilize d f or scree ni n g or baseli ne p ur p oses pr o vi de d t h e 
pr oce d ures met t he pr ot oc ol -s pecifie d criteria a n d were perf or me d wit hi n t he ti me fra m e defi ne d i n 
t he S o A. 
T a ble 7     T ot a l V ol u me of Bl o o d Per S u bject i n E ac h C o h ort 
Ty pe of S a m ple  
Vol u me per 
S a m ple ( m L)  
P art A  
P art  B , 
C o h ort 1  
P art B, 
C o h ort 2  
P art B, 
C o h ort 3  
P art B, 
C o h ort 4  
Bl o o d s a m pli n g 
peri o d  
 
D a y -3 0 ~  
D a y 4  
D a y -3 0 ~ 
D a y 1 5  
D a y -3 0 ~ 
D a y 1 6  
D a y -3 0 ~ 
D a y 1 4  
D a y -3 0 ~ 
D a y 1 4  
C oa g ulati o n 
para meters  
He mat ol o g y  
Cli nical 
c he mistr y test  
Vir ol o g y  
Ser u m 
pre g na nc y t est  
Platelet f u ncti o n 
test 
C Y P 2 C 1 9 
ge n ot y pi n g  
P K sa m ples of 
L T 3 0 0 1  
P K sa m ples of 
As piri n, 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 5 9  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
Cl o pi d o grel 
A pi xa ba n, or  
Da bi gatra n  
N ote: A n i n d welli n g i ntra ve n o us ca n n ula ma y be use d f or bl o o d sa m ple c ollecti o n. If a ma n dari n 
( o bt urat or) is use d, bl o o d l oss d ue t o discar d is n ot e x pecte d. If bl o o d sa m ples are c ollecte d via 
a n i n d welli n g ca n n ul a, a n a p pr o priat e a m o u nt (i.e., 1 m L) of fl ui d sli g htl y greate r t ha n t he dea d 
s pace v ol u me of t he l oc k will be re m o ve d fr o m t he ca n n ul a a n d discar de d bef ore eac h bl o o d 
sa m ple is ta ke n. 
 
9. 1.   
A d verse E ve nts  
T he defi niti o ns of a n A E or S A E ca n be f o u n d i n  A p pe n di x  4 . 
A E s will be re p orte d b y t he partici pa nt  ( or, w he n a p pr o priat e, b y a care gi ver, s urr o gat e, or t he 
partici pa nt 's le gall y a ut h orize d re pres e ntati ve).  
T he I n vesti gat or a n d a n y desi g nees are res p o nsi ble f or detecti n g, d oc u me nti n g, a n d rec or di n g e ve nts 
t hat meet the defi niti o n of a n A E or S A E a n d re m ai n res p o nsi ble f or f oll o wi n g u p A Es t hat are 
seri o us, c o nsi dere d relat e d t o t he st u d y treat me nt or st u d y pr oce d ures, or t hat ca use d t he partici pa nt 
t o disc o nti n ue t he st u d y treat me nt or st u d y. T he s e verit y or i nte nsit y  of eac h A E is t o be assesse d b y 
t he I n v esti gat or acc or di n g t o t he Nati o nal Ca ncer I nstit ute  C o m m o n Ter mi n ol o g y Criteria f or 
A d verse E v e nts ( C T C A E ) v 5. 0 
. 
9. 1. 1.   
Ti m e P eri o d a n d Fre q ue nc y f or C ollecti n g A E a n d S A E Inf or m ati o n   
All A Es a n d S A Es will be c ollecte d fr o m t he si g ni n g of t he I C F u ntil t he f oll o w-u p visit  at t he ti me 
p oi nts s pecifie d i n t he S o A  (Secti o n 2 ). 
Me dical occ urre nces t h at be gi n bef ore t he start of st u d y treat me nt b ut after o btai ni n g i nf or me d c o nse nt 
will  be rec or de d o n t he Me dical Hist or y/ C urre nt Me dical C o n diti o ns secti o n of t he case re p ort f or m 
(C R F ) n ot t he A E secti o n. 
All S A E s will be rec or de d a n d re p orte d t o t he sp o ns or  or desi g nee wit hi n 2 4 h o urs, as i n dicate d i n  
A p pe n di x 4 . T he I n vesti gat or will s u b mit a n y u p date d S A E data t o t he sp o ns or  wit hi n 2 4  h o urs of it 
bei n g a vaila ble.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 0  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
I n v esti gat ors are n ot o bli gate d t o acti vel y see k A E or S A E i n f or mer st u d y partici pa nt s. H o we v er, if 
t he I n vesti gat or lear ns of a n y S A E, i ncl u di n g a deat h, at a n y ti me after a partici pa nt  has bee n 
disc har ge d fr o m t he st u d y, a n d he/s he c o nsi ders t he e ve nt t o be reas o na bl y relate d t o t he st u d y 
treat me nt or st u d y partici pati o n, t he I n v esti gat or m ust pr o m ptl y n otif y t he sp o ns or . 
T he met h o d of rec or di n g, e val uati n g , a n d assessi n g ca usalit y of A E a n d S A E a n d t he pr oce d ures f or 
c o m pleti n g a n d tra ns mitti n g S A E re p orts are pr o vi de d i n  A p pe n di x 4.  
9. 1. 2.   
Met h o d of Detecti n g A E s a n d S A E s 
Care will be ta ke n n ot t o i ntr o d uce bias w he n det ecti n g A Es a n d/ or S A Es. O pe n -e n de d a n d n o n -l ea di n g 
ver bal q uesti o ni n g of t he partici pa nt is t he preferre d met h o d t o i n q uire a b o ut A E  occ urre nces .  
9. 1. 3.   
F oll o w -u p of A E s a n d S A E s 
After t he i nitial A E/ S A E re p ort, t he I n vesti gat or is re q uire d t o pr oacti vel y f oll o w eac h partici p a nt at 
s u bse q ue nt visits/c o ntacts. All S A Es will be f oll o we d u ntil res ol uti o n, sta bilizati o n, t he e ve nt is 
ot her wise e x plai n e d, or t he partici pa nt is l ost t o f oll o w -u p (as defi ne d i n Secti o n 8. 3 ).  
9. 1. 4.   
Re g ul at or y Re p orti n g Re q uire me nts f or S A E s 
Pr o m pt n otificati o n b y t h e I n v esti gat or t o t he sp o ns or  of an  S A E is esse ntial s o t hat le gal o bli gati o ns 
a n d et hical res p o nsi bilities t o war ds t he safet y of s u bjects a n d t he safet y of a st u d y treat me nt u n der 
cli nical i n vesti gati o n are met.  
T he sp o ns or  h as a l e gal res p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d ot her re g ulat or y 
a ge ncies a b o ut t he safet y of a st u d y tr eat me nt u n der cli nical i n vesti gati o n.  T he sp o ns or  will c o m pl y 
wit h c o u ntr y -s pecific re g ulat or y re q uire me nts relati n g t o safet y re p orti n g t o t he re g ulat or y a ut h orit y, 
I nstit uti o nal Re vie w B oar ds (I R B)/I n de pe n d e nt Et hics C o m mittees (I E C) , a n d I n v esti gat ors. 
I n v esti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x p ecte d seri o us a d verse reacti o ns  
( S U S A R) acc or di n g t o l ocal re g ulat or y re q uire me nts a n d sp o ns or  p olic y a n d f or war de d t o 
I n v esti gat ors as necessar y. 
A n I n vesti gat or w h o recei ves a n I n vesti gat or s afet y re p ort d escri bi n g a S A E or ot her s pecific safet y 
i nf or mati o n (e g, s u m mar y or listi n g of S A Es) fr o m t he sp o ns or  will re vie w a n d t he n file it al o n g wit h 
t he I n v esti gat or’s Br oc h ure  a n d will n otif y t he I R B/I E C, if a p pr o priate acc or di n g t o l ocal re q uire me nts . 
9. 1. 5.   
Pre g n a nc y  
Details of all pre g n a ncies i n fe male partici p a nt s a n d, if i n dicate d, fe mal e part ners of male p artici pa nt s 
will be c ollecte d after t he start of st u d y treat me nt an d u ntil 3 0 da ys after t he last d ose . 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 1  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
If a pre g na n c y is re p ort e d, t he I n vesti gat or s h o ul d i nf or m t he s p o ns or wit hi n 2 4 h o urs of lear ni n g of 
t he pre g na n c y a n d s h o ul d f oll o w t he pr oce d ures o utli ne d i n A p pe n di x 5 . 
A b n or mal pre g n a nc y o ut c o mes (e g, s p o nta n e o us a b orti o n, fetal deat h, still birt h, c o n ge nital a n o malies, 
ect o pic pre g n a nc y) are c o nsi dere d S A Es.  
9. 2.   
Tre at me nt of O ver d ose  
T he d ose le vel of L T 3 0 0 1 dr u g pr o d uct will be calc ulate d b y t he I n vesti gat or or a q ualifie d desi g nee 
base d o n t he st u d y s u bject’s b o d y wei g ht. Si nce dr u g acc u m ulati o n is n ot a ntici pate d d ue t o t he s h ort 
half -life of L T 3 0 0 1 a n d s u bjects will o nl y recei ve L T 3 0 0 1 dr u g pr o d uct a d mi nistere d b y a n 
I n v esti gat or or a q ualifi e d desi g ne e a n d u n der cl ose m o nit ori n g, it is  a ntici pate d t hat t he ris k of 
o ver d ose or m e dicati o n err or will be l o w.  
A n o ver d ose is a n y d ose of st u d y treat me nt gi ve n t o a s u bject or ta ke n b y a s u bject t hat e xcee ds t he 
d ose descri b e d i n t he pr ot oc ol. A n y o ver d ose, wit h or wit h o ut ass ociate d A Es, m ust  be pr o m ptl y 
re p orte d t o t he Me dical M o nit or . O ver d oses wit h o ut si g ns or s y m pt o ms d o n ot nee d t o be rec or de d as 
A Es; i n case of a n y A Es ass ociate d wit h t he o ver d ose, t hese s h o ul d be re p orte d o n rele va nt A E/ S A E 
secti o ns i n t he e C R F.  
O ver d oses a n d m e dicati o n err ors will be d oc u me nte d as pr ot oc ol de vi ati o ns a n d c o m m u nicate d  t o t he 
pr oject ma na g er.  
N o s pecifi c t hera p y f or o ver d ose of L T 3 0 0 1 dr u g pr o d uct e xists. I n t he e ve nt of o ver d ose or  me dicati o n 
err or, a p pr o priat e t hera p y f or t he patie nt’s s y m pt o ms a n d cli nical stat us s h o ul d be pr o vi de d.  
9. 3.   
S afet y  Assess me nts   
Pla n ne d ti me p oi nts f or all safet y assess me nts are pr o vi de d i n t he S o A  (Secti o n 2 ). 
9. 3. 1.   
P h ysic al E x a m i n ati o ns 
•  A c o m plete p h ysical e xa mi nati o n 
will i ncl u de, at a 
mi ni m u m, assess me nt s of t he 
Car di o vasc ular, Res pirat or y, Ga str oi ntesti nal a n d Ne ur ol o gical s yste ms. Hei g ht a n d wei g ht 
will als o be meas ure d a n d rec or de d . 
•  I n v esti gat ors s h o ul d pa y s pecial atte nti o n t o cli nical si g ns relate d t o pre vi o us seri o us ill nesses . 
9. 3. 2.   
Vit al Si g ns  
•  B o d y te m perat ure, s yst olic a n d diast olic bl o o d press ure, heart rate, a n d res pira t or y rat e will be 
assesse d after t he s u bject has reste d i n p ositi o n at least 3 mi n utes.  
•  Bl o o d press ure will be assesse d i n s eate d a n d s u pi ne p ositi o n at pre d ose a n d 6 0 mi n utes after 
d osi n g /i nf usi o n, o nl y s u pi ne p ositi o n at 2 0 mi n utes after d osi n g/i nf usi o n . 
•  Bl o o d press ure a n d h eart rate meas ure me nts will be assesse d wit h a c o m pletel y a ut o mate d 
de vice. Ma n u al tec h ni q u es will be use d o nl y if a n a ut o mate d de vice is n ot a vaila ble.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 2  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
9. 3. 3.   
Electr oc a r di o gr a m s 
•  Si n gle  1 2 -lea d E C G will be o btai ne d a s o utli ne d i n t he S o A  (Secti o n  2 ) usi n g a n E C G mac hi ne 
t hat a ut o maticall y calc ulates t he heart rate a n d meas ures R R,  P R, Q R S, Q T, a n d Q Tc F  i nter vals. 
•  E C G will be meas ure d i n a s u pi ne p ositi o n after 5 mi n utes rest.  
9. 3. 4.   
P ulse O xi metr y  
D uri n g Part A, p ulse o xi metr y c o nti n u o us m o nit ori n g will be  perf or me d fr o m pre d ose u p t o 1  h o ur 
after eac h i nf usi o n is i nitiate d. O xi metr y will be rec or de d at pre -d ose a n d 2 0 mi n utes after i nf usi o n is 
i nitiate d (e n d of i nf usi o n). 
9. 3. 5.   
C o a g ul ati o n a n d Pl atelet F u ncti o n  Test  
D uri n g Part A, platelet f u ncti o n test will meas ure o n Da y -1, f oll o wi n g t he first ( D ose 1) a n d last ( D ose 
9) d ose of L T 3 0 0 1 dr u g pr o d uct i nf usi o n  a n d e n d of st u d y visit . C oa g ulati o n ( P T, I N R, a P T T, a n d T T ) 
will be meas ure d d uri n g s cree ni n g , Da y -1, a n d f oll o wi n g t he D ose 1, 4, a n d 9  of L T 3 0 0 1  dr u g pr o d uct 
i nf usi o n a n d f oll o w-u p visit .  
D uri n g Part B, c o a g ulati o n test will be meas ure d i n t he scree ni n g visit. Platelet f u ncti o n test a n d 
c oa g ulati o n tests  will be meas ure d o n Da y -1, f oll o wi n g t he last d ose of as piri n, cl o pi d o grel, a pi xa ba n, 
a n d dabi gatra n  1 5 mi n utes  a n d 6 h o urs 1 5 mi n utes , a n d f oll o wi n g as piri n, cl o pi d o grel, a pi xa ba n a n d 
da bi gatra n c o a d mi nistrati o n wit h t he first a n d last L T 3 0 0 1 dr u g pr o d uct i nf usi o n  a n d f oll o w-u p visit .  
9. 3. 6.   
C li nic al S afet y L a b or at or y Assess me nts 
See  A p pe n di x  2  f or t h e list of cli nical la b orat or y t ests t o be perf or me d a n d t o t he S o A  (Secti o n 2 ) f or 
t he ti mi n g a n d fre q ue n c y.  
T he I n vesti gat or m ust re vie w t he la b orat or y re p ort, d oc u me nt t his re vie w, a n d rec or d a n y cli nicall y 
rele va nt c ha n g es occ urri n g d uri n g t he st u d y i n t he A E  sectio n of t he C R F. T he la b orat or y re p orts m ust 
be file d wit h t he s o urce d oc u me nts.  Cli nicall y si g nifica nt a b n or mal la b orat or y fi n di n gs are t h ose w hic h 
are n ot ass ociate d wit h t he u n derl yi n g disease, u nless j u d ge d b y t he I n vesti gat or t o be m ore s e vere 
t ha n e x pect e d f or t he p artici pa nt 's c o n diti o n. 
All la b orat or y tests wit h val ues c o nsi dere d cli nicall y si g nifica ntl y a b n or mal d uri n g partici pati o n i n t he 
st u d y s h o ul d be re peate d u ntil t he val ues ret ur n t o n or mal or bas eli ne  or are n o l o n ger c o nsi dere d 
cli nicall y si g nifica nt b y t he I n vesti gat or or me dical m o nit or . 
•  If s uc h val ues d o n ot ret ur n t o n or mal/ baseli ne wit hi n a peri o d of ti me j u d ge d reas o na ble b y 
t he I n v esti gat or, t he eti ol o g y s h o ul d be i de ntifie d a n d t he sp o ns or  n ot ifie d. 
•  All pr ot oc ol -re q uire d la b orat or y assess me nts, as defi ne d i n A p pe n di x 2 , m ust be c o n d ucte d i n 
acc or da nce wit h t he la b orat or y ma n ual a n d t he S o A .  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 3  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
•  If la b orat or y val ues fr o m n o n -pr ot oc ol s pecifi e d la b orat or y assess me nts perf or me d at t he 
i nstit uti o n’s local la b orat or y re q uire a c h a n ge i n partici pa nt  ma na g e me nt or are c o nsi dere d 
cli nicall y si g nifica nt b y t he I n v esti gat or (e g, S A E or A E or d ose m o dificati o n) , t he n t he res ults 
m ust be rec or de d i n t he C R F.   
9. 4.   
P h ar m ac o ki netics  
W h ole bl o o d  a n d uri ne sa m ples will be c ollecte d f or meas ure m e nt of plas ma  a n d uri ne  c o n ce ntrati o ns 
of L T 3 0 0 1  as s pecifie d i n t he S o A  (Secti o n 2 ). I nstr ucti o ns f or t h e c ollecti o n a n d ha n dli n g of bi ol o gical 
sa m ples will be pr o vi de d b y t he sp o ns or . T he act u al date a n d ti me ( 2 4-h o ur cl oc k ti me) of eac h sa m ple 
will be rec or de d . 
A n y c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u d y as sess me nts m ust be 
d oc u me nte d a n d a p pr o ve d b y t he rele va nt st u d y t ea m me m ber a n d t he n arc hi ve d i n t he sp o ns or  a n d 
site st u d y files, b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt. T he I R B/I E C will be i nf or me d of a n y 
safet y iss ues t hat re q uir e alterati o n of t he safet y m o nit ori n g sc he me or a me n d me nt of t he I C F. 
T he f oll o wi n g P K para m eters will be esti mate d as practica bl e usi n g act ual sa m ple c ollecti o n ti mes:  
C ma x   
ma xi m u m plas ma c o nce ntrati o n d uri n g a d osi n g i nter val  
C mi n   
tr o u g h plas ma c o nce ntrati o n 
C a v 
mea n stea d y-stat e dr u g c o nce ntrati o n 
tma x  
ti me t o reac h t he ma xi m u m plas ma c o nce ntrati o n 
z 
A p pare nt first -or der t er mi nal eli mi nati o n rate c o nsta nt, calc ulate d b y li near least -
s q uares re gressi o n a nal ysis o n t he ter mi nal l o g-li near p h ase of t h e plas ma 
c o nce ntr at i o n vs ti me c ur ves usi n g at least 3 ti me p oi nts 
A U C 0 -  
area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o i nfi nite ti me, 
calc ulate d as t he s u m of A U C last a n d C last/z, i n w hic h Clast is t he last o bser ve d 
q ua ntifia ble c o nce ntrati o ns  
A U C 0 -t  
area un der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o t he ti me of last 
q ua ntifia ble c o nce ntrati o n, calc ulate d b y t h e li near tra p ez oi dal li near i nter p olati o n 
met h o d  
A U C 0 -2 4  
area u n d er t he plas m a c o nce ntrati o n -ti me c ur ve fr o m ti me 0 t o 2 4 h o urs, calc ulate d 
b y t he li near tra p ez oi dal li near i nter p olati o n met h o d  
A U C 0 -ta u  
A U C o ver t he d osi n g i nter val  at stea d y -state 
M R T
0 - 
Mea n resi de n ce ti me, cal c ulate d as  
𝐴𝑈𝑀𝐶0 −𝜏 +  τ (𝐴𝑈𝐶0 −∝ − 𝐴𝑈𝐶0 −𝜏) 
𝐴𝑈𝐶0 −𝜏
−
𝑇𝐼
2  w here A U M C 0 -τ is 
t he area u n der t he m o me nt c ur ve o ver d osi n g i nter val τ, TI re prese nts i nf usi o n d urati o n. 
t1/ 2,   
eli mi nati o n half -life, cal c ulate d as 0. 6 9 3/
z 
C L  
T otal b o d y cleara nce of t he dr u g fr o m plas ma, cal c ulate d as D os e / A U C 0 -∞ 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 4  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
V z 
A p pare nt v ol u me of distri b uti o n d uri n g t he ter mi nal p hase, calc ulate d as ( D ose / 
A U C 0 -∞) / λz 
V ss 
A p pare nt v ol u me of distri b uti o n d uri n g stea d y state, calc ul ate d as C L x M R T  
Ae x -y  
A m o u nt of dr u g e xcrete d i n uri ne wit hi n a c ollecti o n i nter val ( x t o y h o urs), w here 
t he val ues of x t o y are 0 t o 1 2 a n d 1 2 t o 2 4 
Ae 0 -2 4  
T otal a m o u nt of dr u g e xcrete d i n uri ne o ver t he e ntire c ollecti o n peri o d ( 0 t o 2 4 
h o urs)  
Fe 0 -2 4  
Fracti o n e xcrete d i n uri n e fr o m 0 t o 2 4 h o urs after d osi n g, calc ulate d as Ae 0 -2 4 / 
D ose × 1 0 0  
C Lr   
Re nal cleara nce, cal c ulat e d as Ae 0 -2 4 / A U C0 -∞ 
Racc   
Acc u m ulati o n rati o calc ulate d as A U C 0 -t, 1st d ose/ A U C0 -t, last d ose f or t he m ulti-da y 
L T 3 0 0 1 re gi me ns.  
9. 5.   
P h ar m ac o ge ne tics 
F or Part B C o h ort 2 o nl y, a  bl o o d sa m ple f or i de ntificati o n of C Y P 2 C 1 9 p o or meta b olizers 
( C Y P 2 C 1 9 * 2/ * 2, * 2/ * 3, or * 3/ * 3 ge n ot y pe) will be c ollecte d fr o m s u bjects w h o ha ve c o ns e nte d t o 
partici pate i n t he ge netic a nal ysis c o m p o ne nt of t he st u d y. Partici pati o n is ma n dat or y f or Part B C o h ort 
2 . 
9. 6.   
Me dic al Res o urce Utiliz ati o n a n d He alt h Ec o n o mic s 
N ot a p plica ble  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 5  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
1 0.   
St atistic al C o nsi der ati o ns  
1 0. 1.  
S a m ple Size Deter mi n ati o n   
Sa m ple sizes were n ot b ase d o n statistical c o nsi derati o ns. Si xtee n s u bjects i n Part A, a n d 1 2 s u bjects 
per c o h ort i n Part B are d ee me d s uffi cie nt t o ac hie ve t he st u d y o bjecti ves.   
1 0. 2.   
P o p ul ati o ns f or A n al yses  
F or p ur p oses of a n al ysis, t he f oll o wi n g p o p ulati o ns are defi ne d:  
P o p ul ati o n  
Descri pti o n  
E nr olle d  
All s u bjects w h o si g n t he I C F 
Safet y  A nal ysis Set  ( S A S)  
All s u bjects assi g ne d t o st u d y treat me nt a n d w h o t o o k at least 1 
d ose of st u d y treat me nt. S u bjects will be a nal yze d acc or di n g t o t he 
treat me nt t he y act uall y recei ve d. 
P har mac o ki netic  A nal ysis 
Set  ( P K A S) 
All s u bjects assi g ne d t o st u d y treat me nt, w h o t o o k at least 1 d ose of 
st u d y treat me nt, a n d pr o vi de d at least 1 P K sa m ple. S u bjects ma y be 
e xcl u de d fr o m t he P K A S o n a n i n di vi d ual basis, u p o n re vie w of all 
rec or ds t hat h a ve t he p ot e ntial t o affect t he P K data (e. g., d osi n g 
rec or ds, A Es, bl o o di n g sa m pli n g rec or ds, c o n c o mita nt me dicati o ns 
else t ha n as piri n/cl o pi d o grel/a pi xa ba n/ da bi g atra n , pr ot oc ol 
de viati o ns of diet restricti o n ). 
1 0. 3.  
St atistic al A n al yses  
T he Statistical A nal ysis Pla n ( S A P) will be de vel o pe d a n d fi nalize d bef ore data base l oc k a n d will 
descri be t he partici pa nt p o p ulati o ns t o be i ncl u de d i n t he a nal yses, a n d pr oce d ures f or acc o u nti n g f or 
missi n g, u n use d, a n d s p uri o us data. T his secti o n is a s u m mar y of t he pl a n ne d statistical a nal yses of t h e 
e n d p oi nts . B aseli ne val ue  is defi ne d as t he last n o n-missi n g meas ure me nt pri or t o t he i nitiati o n of a n y 
st u d y treat me nt u nless s pecifie d els e w here.  
1 0. 3. 1.   
S afet y A n al yses  
All safet y a n al yses will be perf or me d o n t h e Safet y A nal ysis Set . A d verse e ve nts will be c o de d b y 
S yste m Or ga n Class  a n d Preferre d Ter m usi n g t he latest versi o n of Me d D R A. I nci de nces of T E A Es 
(ie, e ve nts t hat st arte d after e x p os ure t o st u d y dr u g or w ors e ne d i n s e verit y after d osi n g) will be 
prese nte d b y d os e gr o u p , ma xi m u m se verit y , a n d relati o ns hi p t o st u d y me dicati o n.  
Safet y data will be s u m marize d t hr o u g h a p pr o priat e data ta b ulati o ns a n d sta n dar d descri pti ve statistics 
b y treat me nt. F or eac h c o nti n u o us la b orat or y para meter, res ults will be cate g orize d as l o w, n or mal, or 
hi g h base d  o n t he la b orat or y n or mal ra n g es. S hift ta bles ca pt uri n g t he n u m ber a n d perce nta ge of 
s u bjects s hifti n g fr o m t hese baseli ne t o p ost-baseli ne cate g ories will be pres e nte d.  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 6  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
T he ass ociati o n of A Es, la b orat or y res ults, c oa g ulati o n para meters, platel et f u ncti o n test, vital si g n 
meas ure me nts, o xi metr y,  a n d E C G res ults wit h t he treat me nt of st u d y dr u g or P K para meters ma y als o 
be e x pl ore d. If a p pr o priate, statistical m o deli n g will be perf or me d t o f urt her c haracterize t h e 
ass ociati o ns me nti o ne d a b o ve. All o ut -of -ran ge a n d cli nicall y si g nifica nt la b orat or y res ults will be 
i de ntifie d i n s u bject data listi n gs. T he n u m ber a n d perce nta ge of s u bjects i n eac h d ose gr o u p wit h 
n or mal a n d a b n or mal p h ysical e xa mi nati o n res ults will be prese nte d f or e val uati o ns at baseli ne a n d 
fi nal visit. 
F or eac h b o d y s yste m, c h a n ges i n t he s u bjects’ fi n di n gs fr o m bas eli ne t o fi nal visit ( n o c h a n ge, n or mal 
t o a b n or mal, or a b n or m al t o n or mal) will be ta b ulate d f or eac h d ose gr o u p. 
To i n vesti gate w het her platelet f u ncti o n t est is pr ol o n ge d w he n c o a d mi nstrate d wit h L T 3 0 0 1 dr u g 
pr o d uct, platelet  f u ncti o n test o bser ve d u n der si n gle treat me nt of as piri n,  cl o pi d o grel, a pi xa ba n or 
da bi gatra n will be c o m pare d wit h platelet  f u ncti o n test o bser ve d u n der c oa d mi n istrati o n wit h L T 3 0 0 1 
dr u g pr o d uct.  Platelet  f u ncti o n test will be s u m marize d wit h sta n dar d d escri pti ve statistics b y treat me nt. 
S hift ta bles ca pt uri n g t he n u m ber a n d perce nt a ge of s u bjects s hifti n g fr o m baseli ne t o p ost -baseli ne 
cate g ories will be prese nt e d.  
1 0. 3. 2.   
P h ar m ac o ki netic  A n al yses  
All P K a nal yses will be perf or me d o n t he P har mac o ki netic A nal ysis Set . T he  P K para meters will be 
calc ulate d, as a p pr o priate, usi n g a n o n -c o m part me ntal a p pr oac h.  
Plas ma c o nce ntrati o ns will be s u m marize d b y c o h ort o ver eac h sc he d ule d sa m pli n g ti me usi n g 
descri pti ve  statistics. I n di vi d ual plas ma c o nce ntrati o n data vers us act ual ti me p oi nts will be prese nte d 
i n listi n gs. P har mac o ki netic para meters will be s u m marize d b y d ose usi n g descri pti ve statistics. 
I n di vi d ual P K para meters will be prese nte d i n a d ata listi n g.  
T h e effect of as piri n, cl o pi d o grel, a pi xa ba n or da bi gatra n o n t he P K of L T 3 0 0 1, as well as t he effect 
of L T 3 0 0 1 o n t he P K of as piri n, cl o pi d o grel, a pi xa ba n or da bi gatra n, will be assesse d b y c o m pari n g 
P K para meters of L T 3 0 0 1 a n d t hese c o nc o mita nt me dicati o ns . A li near mi x e d-effects m o del wit h fi xe d 
fact ors f or C o h ort a n d Da y ( da y of wit h/ wit h o ut c o nc o mita nt dr u g use), a n d s u bject as ra n d o m effect 
o n l o g P K -para meter will be use d t o calc ulate 9 0 % c o nfi de nce i nter vals f or t he ge o metric mea n rati o 
of t he A U C 0 -t, A U C 0 -∞, A U C 0 -ta u a n d C ma x . Differe nces bet w ee n treat me nts w he n L T 3 0 0 1 dr u g pr o d uct 
was a d mi nistere d al o ne or wit h as piri n, cl o pi d o grel, a pi xa ba n or da bi gatra n will be cal c ulate d f or 
L T 3 0 0 1, as piri n, cl o pi d o grel, a pi xa ba n, a n d da bi gatra n usi n g rati os of ge o metric least s q uares mea n 
a n d 9 0 % c o nfi de n ce i nter vals ( CI). T he criteria of 9 0 % CI wit hi n 5 0 -2 0 0 % of wea k -effect b o u n daries 
will be firstl y use d f or assess me nt. O nl y w he n t he first criteria are satisfie d, t he sec o n d criteria of 9 0 % 
CI wit hi n 8 0 -1 2 5 % of n o -effect b o u n daries will be use d f or f urt her ass ess me nt.   
T o i n vesti gate w het h er t h e d ose of L T 3 0 0 1 dr u g pr o d uct is acc u m ulate d i n t he 3 -da y TI D re gi me n, t he 
p ote ntial d ose acc u m ulati o n effect will be assesse d b y c o m pari n g P K para meters  of t he first d ose a n d 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 7  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
t he last d ose i n t he m ulti -da y TI D re gi me n of L T 3 0 0 1 dr u g pr o d uct . T he c o m paris o ns will be c o n d ucte d 
f or occasi o ns w he n L T 3 0 0 1 is al o ne or is c oa d mi nistrate d wit h as piri n, cl o pi d o grel, a pi xa ba n, or  
da bi gatra n.  P K para meters f or c o m paris o n i ncl u de A U C 0 -t a n d C ma x ..  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 8  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
1 1.   
Refere nces  
1.  Al dee n A, Pir otte M. F oc us o n: Ac ut e isc he mic str o ke. A merica n C olle ge of E mer ge nc y P h ysicia ns 
Ne ws. 2 0 0 9. 
A vaila ble fr o m htt ps:// w w w.ace p. or g/ Cli nical -Practice M a na ge me nt/ F oc us -O n --
Ac ute -Is c he mic-Str o ke/.  
2.  De b P, S har ma S, Hassa n K M. Pat h o p h ysi ol o gic mec ha nis ms of ac ut e isc he mic str o ke: A n 
o ver vie w wit h e m p hasis o n t hera pe utic si g nifica nce be y o n d t hr o m b ol ysis. Pat h o p h ysi ol o g y. 
2 0 1 0; 1 7( 3): 1 9 7 -2 1 8. 
A vaila ble 
fr o m 
htt p:// w w w. pat h o p h ysi ol o g yj o ur nal.c o m/article/ S 0 9 2 8 4 6 8 0( 0 9) 0 0 1 3 6 -9/ p df.  
3.  De maersc hal k B M, Klei n d orfer D O, A de o ye O M, et al; o n be half of t he A merica n Heart 
Ass ociati o n Str o ke C o u n cil a n d C o u ncil o n E pi de mi ol o g y a n d Pre ve nti o n. Scie ntific rati o nale f or 
t he i ncl usi o n a n d e x cl usi o n criteria f or i ntra ve n o us alte plase i n ac ute isc he mic str o ke: a state me nt 
f or healt hcare pr ofessi o nals fr o m t he A merica n Heart Ass ociati o n/ A merica n Str o ke Ass ociati o n. 
Str o ke. 2 0 1 6; 4 7( 2): 5 8 1 – 6 4 1. A vaila ble fr o m htt p://str o ke.a haj o ur nals. or g/c o nte nt/ 4 7/ 2/ 5 8 1.   
4.  Ka ur J, Z ha o Z, Klei n G M, et al. T he ne ur ot o xicit y of tiss ue plas mi n o ge n acti vat or? J Cere b Bl o o d 
Fl o w   
Met a b.   
2 0 0 4; 2 4( 9): 9 4 5 -9 6 3.   
A vaila ble   
fr o m 
htt p://jc b.sa ge p u b.c o m/c o nte nt/ 2 4/ 9/ 9 4 5.f ull. p df + ht ml.  
5.  K u o T H, Pe n g H Y, F u R H, et al. A bstract 1 7 3: A n o vel d ual f u ncti o n m olec ule f or t he treat me nt of 
ac ute isc he mic str o k e. I nter nati o nal Str o ke C o nfere n ce Oral A bst racts. Str o ke. 2 0 1 6; 4 7: A 1 7 3. 
A vaila ble fr o m htt p://str o ke.a haj o ur n als. or g/c o nte nt/ 4 7/ S u p pl _ 1/ A 1 7 3.   
6.  M ozaffaria n D, Be nja mi n EJ, G o A S, et al;  o n be half of t he A merica n Heart Ass ociati o n Statistics 
C o m mittee a n d Str o ke St atistics S u bc o m mittee. Heart disease a n d str o k e st atistics —  2 0 1 6 u p date: 
a re p ort fr o m t he A merica n Heart Ass oci ati o n. Circ ulati o n. 2 0 1 6; 1 3 3( 4):e 3 8 -e 3 6 0. A vaila ble fr o m 
htt p://c irc.a haj o ur nals. or g/c o nte nt/ 1 3 3/ 4/e 3 8.l o n g.   
7.  N o ur 
M, Scalz o F, Lie bes ki n d D S. Isc he mia -re perf usi o n i nj ur y i n str o ke. I nt er ve nt Ne ur ol. 
2 0 1 2; 1: 1 8 5 -1 9 9. A vaila ble fr o m htt ps:// w w w. nc bi. nl m. ni h. g o v/ p mc/articles/ P M C 4 0 3 1 7 7 7/.   
8.  R ot h J M. Rec o m bi na nt tiss ue plas mi n o ge n acti vat or f or t he treat me nt of ac ute isc he mic str o ke. Pr oc 
( Ba yl U ni v Me d Ce nt). 2 0 1 1; 2 4( 3): 2 5 7– 9.  
9.  Sacc o R L, Kas ner S E, Br o deric k J P, et al; o n b e half of t he A merica n Heart Ass o ciati o n Str o ke 
C o u ncil, C o u ncil o n Car di o vasc ular S ur ger y a n d A nest hes ia, C o u ncil o n Car di o vasc ular Ra di ol o g y 
a n d I nt er ve nti o n, C o u ncil o n Car di o vasc ular a n d Str o ke N ursi n g, C o u ncil o n E pi de mi ol o g y a n d 
Pre ve nti o n, C o u ncil o n Peri p heral Vasc ul ar Disease, a n d C o u ncil o n N utriti o n, P h ysical Acti vit y 
a n d Meta b olis m. A n u p date d d efi niti o n of str o ke f or t he 2 1 st ce nt ur y: a state me nt f or healt hcare 
pr ofessi o nals fr o m t he 
A merica n 
Heart 
Ass o ciati o n/ A merica n Str o ke 
Ass ociati o n. Str o ke. 
2 0 1 3; 4 4( 7): 2 0 6 4 -2 0 8 9. A vaila ble fr o m htt p://str o ke.a haj o ur nals. or g/c o nte nt/ 4 4/ 7/ 2 0 6 4.a bstract.  
1 0.  Sc ot tis h I nterc olle giate G ui deli nes Net w or k ( SI G N). M a na ge m e nt of patie nt wit h str o ke or TI A: 
assess me nt, i n vesti gati o n, i m me diate ma na ge m e nt a n d sec o n d ar y pre ve nti o n. A nati o nal cli nical 
g ui deli ne.  
Dece m ber 
2 0 0 8 
[cite d 
2 0 1 7  
Mar 
2 0] 
[ 7 8 
s cree ns].  
A vaila ble 
fr o m: 
htt p:// w w w.si g n.ac. u k/assets/si g n 1 0 8 _c osti n g _re p ort. p df.  
1 1.  Wa di wala M F, S o na walla A, Ka mal A K. W hat is t he r ole of free ra dical sca ve n gers i n ac ute str o ke? 
J   
Pa k   
Me d   
Ass oc.   
2 0 1 2; 6 2( 5): 5 1 2-5 1 3.   
A vaila ble   
fr o m 
htt p:// w w w.j p ma. or g. p k/f ull _article _te xt. p h p?a rticle _i d = 3 4 1 3.   
1 2.  W orl d  
Heart 
Fe d erati o n 
( W H F). 
Str o ke. 
2 0 1 6.  
A vaila ble 
fr o m 
htt p:// w w w. w orl d -
heartfe derati o n. or g/car di o vasc ular -h ealt h/str o ke/.  
 
 
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 6 9  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
 
 
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 7 0  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
1 2.   
A p pe n dices  
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 7 1  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
A p pe n di x 1 : A b bre vi ati o ns a n d Ter ms  
A b bre vi ati o n   
Defi niti o n  
A E  
a d verse e ve nt  
Ae x -y 
a m o u nt of dr u g e xcrete d i n uri ne wit hi n a c ollecti o n i nter val ( x t o y  h o urs)  
Ae 0 -2 4 
t otal a m o u nt of dr u g e xcrete d i n uri ne o ver t he e ntire c ollecti o n peri o d ( 0 t o 
2 4  h o urs)  
AI S  
ac ute isc he mic str o k e  
a P T T 
acti vate d partial t hr o m b o plasti n ti me  
A U C  
area u n d er  t he c ur ve 
A U C 0 - 
area u n d er t he c o nce ntrati o n -ti me c ur ve fr o m zer o t o i nfi nit y 
A U C 0 -t 
area u n d er t he c o nce ntrati o n -ti me c ur ve fr o m zer o u p t o t he last ti me p oi nt 
wit h a meas ura bl e c o nce ntrati o n  
A U C 0 -ta u  
area u n d er t he c o nce ntrati o n -ti me c ur ve o ver t he d osi n g i nter val τ at stea d y-
state 
BI D  
t wice dail y 
B L Q  
bel o w t he li mit of q ua ntificati o n  
C F R  
C o de of Fe deral Re g ulati o ns  
C a v  
Mea n stea d y -st ate dr u g c o nce ntrati o n 
C L  
t otal b o d y cleara n ce 
C Lr  
re nal cleara nce 
C ma x  
ma xi m u m o bser ve d plas ma c o nce ntrati o n  
C mi n  
Tr o u g h plas ma c o nce ntrati o n  
C R F  
case re p ort f or m  
C V  
c oefficie nt of variati o n  
D B P  
diast olic bl o o d press ure  
E C G  
electr ocar di o gra m  
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 
Fe 0 -2 4 
fracti o n e x cret e d i n uri ne fr o m 0 t o 2 4 h o urs after d osi n g  
G C P  
G o o d Cli nica l Practice 
G L P  
G o o d La b orat or y Practice  
H Bs A g  
he patitis B s urface a nti ge n  
H B V  
he patitis B vir us  
Hct  
he mat ocrit  
H C V  
he patitis C vir us  
H g b  
he m o gl o bi n  
HI V  
h u ma n i m m u n o deficie nc y vir us  
H V  
healt h y v ol u nteer  
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 u ncil o n Har m o nisati o n 
I E C  
I n de pe n de nt Et hics C o m mittees 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 7 2  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
I R B 
i nstit uti o nal re vie w b oar d 
I V 
i ntra ve n o us 
λ z 
a p pare nt first -or der ter mi nal eli mi nati o n rate c o nst a nt  
M R T  
mea n resi de n ce ti me  
n  
n u m ber of o bser vati o ns  
P A F  
platelet acti vati o n fac t or 
P D  
p har mac o d y n a mic  
PI  
Pri nci pal I n vesti gat or 
P K  
p har mac o ki netic  
P K A S  
p har mac o ki netic a nal ysis set  
P T  
pr ot hr o m bi n ti me  
q 1 2 h  
e ver y 1 2 h o urs  
q 3 h  
3 h o urs a part  
rt P A  
rec o m bi na nt tiss ue-t y pe plas mi n o ge n acti vat or 
S A E  
seri o us a d verse e v e nt 
S A P  
Statistical  A nal ysis Pla n  
S B P  
s yst olic bl o o d press ure 
S D  
sta n dar d de viati o n 
S o A  
sc he d ule of acti vities 
S R M  
Safet y Re vie w Meeti n g  
T E A E  
treat me nt-e mer ge nt a d verse e ve nt  
TI D  
t hree ti mes a da y 
T T  
t hr o m bi n ti me 
tma x  
ti me t o reac h t he o bser ve d ma xi m u m ( pea k) c o n ce ntrati o n  
t1/ 2 
eli mi nati o n half -life 
U S  
U nite d States  
V ss 
v ol u me of distri b uti o n at stea d y state  
Vz  
A p pare nt v ol u me of distri b uti o n d uri n g t he ter mi nal p hase  
 
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 7 4  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
•  p H, gl uc ose, pr otei n, bl o o d, ket o nes, bilir u bi n, ur o bili n o ge n, nitrite, le u k oc yte 
esterase b y di pstic k  
•  Micr osc o pic e x a mi nati o n (if bl o o d or pr otei n is a b n or mal)  
Ot her 
Scree ni n g 
Tests  
•  alc o h ol breat h test a n d uri ne dr u g scree n (t o i ncl u de at mi ni m u m: 
a m p heta mi nes, bar bit urates, c ocai n e, o piates, ca n n a bi n oi ds a n d 
be nz o diaze pi nes)  
•  Ser u m h u ma n c h ori o nic g o na d otr o pi n ( h C G) pre g na nc y test  
•  Ser ol o g y ( HI V a nti b o d y, he patitis B s urface a nti ge n [ H Bs A g], a n d he p atitis C 
vir us a nti b o d y or s pecif y ot her tests)  
•  C o vi d -1 9  
•  C Y P 2 C 1 9 ge n ot y pi n g test  
 
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 7 5  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
A p pe n di x 3 : St u d y G o ver n a nce C o nsi der ati o ns  
Re g ul at or y a n d Et hic al C o nsi der ati o ns  
T his st u d y will be c o n d ucte d i n acc or da n ce wit h t he pr ot oc ol a n d wit h  t he f oll o wi n g: 
•  C o nse ns us et hical pri nci ples deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he Declarati o n 
of Helsi n ki a n d C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical Scie nces ( CI O M S) 
I nter nati o nal Et hical G ui deli nes 
•  A p plica ble I C H Go o d C li nical P ractice ( G C P) G ui deli nes  
•  A p plica ble la ws a n d re g ulati o ns 
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C F, I n vesti gat or Br oc h ure , a n d ot her rele va nt d oc u me nts ( e g,  
a d vertise me nts) m ust be s u b mitte d t o a n I R B/I E C b y t he I n vesti gat or a n d re vie we d a n d a p pr o ve d b y 
t he I R B/I E C bef ore t he st u d y is i nitiate d.  
A n y a me n d me nts t o t he pr ot oc ol will re q uire I R B /I E C a p pr o val bef ore  i m ple me ntati o n of c ha n g es 
ma de t o t he st u d y desi g n, e xce pt f or c ha n g es necessar y t o eli mi nate a n i m me diate hazar d t o st u d y 
partici pa nt s.  
T he I n vesti gat or will be res p o nsi ble f or t he f oll o wi n g: 
•  Pr o vi di n g writte n s u m maries of t he stat us of t he st u d y t o t he  I R B/IE C a n n uall y or m ore 
fre q ue ntl y i n acc or da nce wit h t he re q uire me nts, p olicies, a n d pr oce d ures esta blis he d b y t he 
I R B/IE C  
•  N otif yi n g t he I R B/I E C of S A E s or ot her si g nifica nt safet y fi n di n gs as re q uire d b y I R B/I E C 
pr oce d ures  
•  Pr o vi di n g o versi g ht of t he  c on d uct of t he st u d y at t he site a n d a d here nce  t o re q uire me nts of 
2 1 C F R, I C H g ui deli nes, t he I R B/I E C, E ur o pea n re g ulati o n 5 3 6/ 2 0 1 4 f or cli nical st u dies (if 
a p plica ble), a n d all ot her a p plica ble l ocal re g ulati o ns  
Fi n a nci al Discl os ure  
I n v esti gat ors a n d s u b-I nvesti gat or s will pr o vi de t he s p o ns or wit h s ufficie nt, acc urate fi na nci al 
i nf or mati o n as re q ueste d t o all o w t he s p o ns or t o s u b mit c o m plete a n d acc urate fi na n cial certificati o n 
or discl os ure state me nts t o t he a p pr o priate re g ul at or y a ut h orities. I n v esti gat ors are res p o nsi ble f or 
pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t he c o urse of t he st u d y a n d f or 1 year after 
c o m pleti o n of t he st u d y.  
I nf or me d C o nse nt Pr ocess 
C o nse nt f or C o vi d -1 9 testi n g  
•  A c o nse nt f or m f or C o vi d -1 9 testi n g will be se nt electr o ni call y t o p ote ntial partici pa nts bef ore 
sc he d uli n g scree ni n g. Testi n g is ma n dat or y f or all partici pa nts. 
•  T he partici pa nts will date a n d si g n t he f or m a n d bri n g it wit h t he m o n t he first da y of scree ni n g.  
C o nse nt t o partici pate i n t he st u d y  
•  T he I n vesti gat or or his/ h er re pres e ntati ve will e x plai n t he nat ure of t h e st u d y t o t he partici p a nt 
or his/ her le gall y a ut h ori ze d re prese nt ati ve a n d a ns wer all q uesti o ns re g ar di n g t he st u d y.  
•  Partici pa nts m ust be i nf or me d t hat t heir partici pati o n is v ol u ntar y. Partici pa nts will be re q uire d 
t o si g n a state me nt of i nf or me d c o nse nt t hat m eets t he re q uire me nts of 2 1 C F R 5 0, l ocal 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 7 6  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
re g ulati o ns, I C H g ui deli nes, Healt h I ns ura nce P orta bilit y a n d Acc o u nta bilit y Act ( HI P A A) 
re q uire me nts, w h ere a p plica ble, a n d t he I R B/I E C or st u d y ce nter.  
•  T he me dical rec or d m ust i ncl u de a state me nt t hat writte n i nf or me d c o nse nt was o btai ne d bef ore 
t he partici pa nt was e nr olle d i n t he st u d y a n d t h e dat e o n w hic h t h e writte n c o nse nt was o btai ne d. 
T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust al s o si g n t he I C F. 
•  Partici pa nts m ust be re -c o nse nte d t o t he m ost c urre nt versi o n of t he I C F(s) d uri n g t heir 
partici pati o n i n t he st u d y.  
•  A c o p y of t he I C F(s) m ust be pr o vi de d t o t he partici pa nt or t he partici pa nt’s le gall y a ut h orize d 
re pres e ntati ve.  
T he I C F will c o ntai n a s e parat e secti o n t hat a d dresses t he use of re mai ni n g ma n dat or y s a m ples f or 
o pti o nal e x pl orat or y res earc h. T h e I n vesti gat or or a ut h orize d desi g nee will e x plai n t o eac h p artici pa nt 
t he o bjecti ves of t h e e x pl orat or y researc h. Parti ci pa nts will be t ol d t hat t he y are free t o ref use t o 
partici pate a n d ma y wit h dra w t heir c o nse nt at a n y ti me a n d f or a n y reas o n d uri n g t he st ora ge peri o d. 
A se parat e si g nat ure will be re q uire d t o d oc u me nt a partici pa nt's a gree m e nt t o all o w a n y re mai ni n g 
s peci me ns t o b e use d f or e x pl orat or y researc h. Partici pa nts w h o decli ne t o partici pate i n t his o pti o nal 
researc h will n ot pr o vi de t his se parate si g nat ure. 
D at a Pr otecti o n  
•  Partici pa nts will be assi g ne d a u ni q ue i de ntifier b y t he sp o ns or . A n y partici pa nt rec or ds or 
datasets t hat are tra nsferre d t o t he sp o ns or  will c o ntai n t he i de ntifier o nl y; partici pa nt na mes 
or a n y i nf or mati o n w hic h w o ul d ma ke t he partici p a nt i de ntifia ble will n ot be tra nsferre d.  
•  T he partici pa nt m ust be i nf or me d t hat his/ her pers o nal st u d y-relate d d ata will be use d b y  the 
sp o ns or  i n acc or da nce wit h l ocal data pr otecti o n la w. T he le vel of discl os ure m ust als o be 
e x plai ne d t o t he partici p a nt.  
•  T he partici pa nt m ust be i nf or me d t hat his/ her me dical rec or ds ma y be e xa mi ne d b y Cli nical 
Q ualit y Ass ura nce a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he sp o ns or , b y 
a p pr o priate I R B/I E C me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities.  
P u bl ic ati o n P olic y 
T he res ults of t his st u d y ma y be p u blis he d or pres e nte d at scie ntific meeti n gs.  If t his is f oresee n, t h e 
I n v esti gat or a grees t o s u b mit all ma n uscri pts or a bstracts t o t he sp o ns or bef ore  s u b missi o n. T his 
all o ws t he sp o ns or t o pr otect pr o priet ar y i nf or mati o n a n d t o pr o vi de c o m me nts.   
T he sp o ns or will c o m pl y wit h t he re q uire me nts f or p u blicati o n of st u d y res ults.  I n acc or da nce wit h 
sta n dar d e dit orial a n d et hical practice, t he sp o ns or will ge nerall y s u p p ort p u blicati o n of m ultice nter 
st u dies o nl y  i n t heir e ntiret y a n d n ot as i n di vi d ual site data.  I n t his case, a c o or di nati n g I n v esti gat or 
will be desi g nate d b y m ut ual a gree m e nt.  
A ut h ors hi p will be deter mi ne d b y m ut ual a gree m e nt a n d i n li ne wit h I nt er nati o nal C o m mittee of 
Me dical J o ur nal E dit ors a ut h ors hi p re q uire m e nts.  
Disse mi n ati o n of Cli nic al St u d y  D at a  
A cli nical st u d y re p ort will be pre pare d wit h refere nce t o I C H G ui da nce E 3 t o i ncl u de:  
•  details of w here t he st u d y was carrie d o ut,  
•  dates of t he start a n d c o m pleti o n of eac h peri o d of t he st u d y, 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 7 7  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
•  details of t he i n vesti gati o nal pr o d uct (I P) a n d a state me nt of pr o d ucti o n will be pr o vi de d b y 
L u m osa  
•  a state me nt c o nfir mi n g t hat t he a p plica ble I R B/I E C ga ve writte n a p pr o val f or t he st u d y i n 
acc or da nce wit h l ocal re g ulati o ns,  
•  a de m o gra p hic listi n g f or all partici pa nts,  
•  a list of all A Es acc or di n g t o I P,  
•  details of a n y occ urre nces w hic h ma y be of si g nifi ca nce t o t he st u d y o utc o me,  
•  details of all o perati o ns, calc ulati o ns a n d tra nsf or mati o ns perf or me d o n t h e re p orte d data,  
•  t he S A P a n d re p ort will be pr od uce d b y L u m osa or t heir a g e nts a n d will b e i nc or p orate d i nt o 
t he fi nal re p ort, 
•  all data fr o m a n y wit h dra w n partici pa nt n ot i ncl u d e d i n t he statistical a nal ysis,  
•  a scie ntific i nter pretati o n of t he res ults,  
•  a descri pti o n of t he st u d y met h o ds use d.  
C o nsi derati o n will be gi ve n t o a n y c o m me nts o n a draft re p ort. T he re p ort will i nc or p orate t he 
a nal ytical a n d statistical res ults a n d m et h o ds pr o d uce d b y t he S p o ns or or t heir a g e nts. A fi nal re p ort 
will be pre pare d t o c o ntai n all t h ose s ecti o ns i n t h e draf t a n d a state me nt of c o m plia nce c o veri n g all 
t he areas of t he st u d y c o n d ucte d at t he i n vesti gati o nal site a n d t he re p ort, wit h G C P. T he re p ort will 
be iss ue d u n der t he S p o ns or’s res p o nsi bilit y.  
W here re q uire d b y t he a p plica ble re g ulat or y re q uire me nts, a n In vesti gat or  si g nat or y will be i de ntifie d 
f or t he a p pr o val of t he cli nical st u d y re p ort. T he I n v esti gat or will be pr o vi de d reas o na bl e access t o 
statistical ta bles, fi g ures, a n d rel e va nt re p orts a n d will ha ve t he o p p ort u nit y t o re vie w c o m plete st u d y 
res ults. T he S p o ns or will als o pr o vi de t he I n vesti g at or wit h t he f ull s u m mar y of st u d y res ults.  
D at a Q u alit y Ass ur a nce  
•  All partici pa nt  data relati n g t o t he st u d y will be rec o rde d o n pri nte d or electr o nic C R F u nless 
tra ns mitte d t o t he sp o ns or  or desi g nee electr o nic all y (e g, la b orat or y data). T he I n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he C R F.  
•  T he I n vesti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce dat a) t hat s u p p orts t he 
i nf or mati o n e ntere d i n t h e C R F.  
•  T he I n vesti gat or m ust per mit st u d y -relate d m o nit ori n g, a u dits, I R B/I E C re vie w, a n d 
re g ulat or y a g e nc y i ns pe cti o ns a n d pr o vi d e direct access t o s o urce data  d o c u me nts.  
•  T he sp o ns or  or desi g ne e is res p o nsi ble f or t he dat a ma na ge m e nt of t his st u d y i ncl u di n g 
q ualit y c hec ki n g of t he d ata.  
•  St u d y m o nit ors will perf or m o n g oi n g s o urce data verificati o n t o c o nfir m t hat data e ntere d 
i nt o t he C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m s o urce 
d oc u me nts; t hat t he safet y a n d ri g hts of partici pa nt s are bei n g pr otecte d; a n d t hat t he st u d y is 
bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot o c ol a n d a n y ot her st u d y 
a gree m e nts, I CH  G C P, a n d all a p plica ble re g ulat or y re q uire m e nts.  
•  Rec or ds a n d d o c u me nts, i ncl u di n g si g ne d I C F s, p ertai ni n g t o t he c o n d uct of t his st u d y m ust 
be retai ne d b y t h e I n vesti gat or f or 2  years after st u d y c o m pleti o n u nless l ocal re g ulati o ns or 
i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y be d estr o ye d d uri n g 
t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he sp o ns or . N o rec or ds ma y be 
tra nsferre d t o a n ot her l ocati o n or part y wit h o ut writte n n otificati o n t o t he sp o ns or .  

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 7 8  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
S o urce D oc u me nts  
S o urce d oc u me nts pr o vi d e e vi de nce f or t h e e xiste n ce of t he p artici pa nt a n d s u bsta ntiate t he i nte grit y 
of t he data c ollecte d. S o urce d oc u m e nts are file d at t he I n v esti gat or’s site. 
Data re p orte d o n t he C R F  o r e ntere d i n t he e C R F  t hat are tra nscri be d fr o m s o urce d oc u m e nts m ust 
be c o nsiste nt wit h t he s o urce d oc u m e nts or t he discre pa n cies m ust be e x pl ai ne d. T he I n v esti gat or 
ma y nee d t o re q u est pre vi o us me dical rec or ds or tra nsfer rec or ds, de pe n di n g o n t he st u d y. A ls o, 
c urre nt me di cal rec or ds m ust be a vaila ble.  
Defi niti o n of w hat c o nstit utes s o urce data ca n b e f o u n d i n t he St u d y Ma n ual. 
St u d y a n d Site Cl os ure  
T he sp o ns or desi g ne e res er ves t he ri g ht t o cl ose t h e st u d y site or ter mi nate t he st u d y at a n y ti me f or 
a n y reas o n at t he s ole dis creti o n of t he s p o ns or. St u d y sites will be cl ose d u p o n st u d y c o m pleti o n. A 
st u d y site is c o nsi dere d cl ose d w he n all re q uire d d oc u me nts a n d st u d y s u p plies ha ve bee n c ollecte d 
a n d a st u d y -site cl os ure visit has bee n perf or me d. 
T he I n vesti gat or ma y i nitiate st u d y -site cl os ure at a n y ti me, pr o vi de d t here is reas o na ble ca use a n d 
s ufficie nt n otice is gi ve n i n a d va nce of t he i nte n de d ter mi nati o n. 
Reas o ns f or t he earl y cl os ure of a st u d y site b y t he s p o ns or or I n vesti gat or ma y i ncl u de b ut are n ot 
li mite d t o: 
•  Fail ure of t he I n vesti gat or t o c o m pl y wit h t he pr ot oc ol, t he re q uire me nts of t he I R B/I E C or 
l ocal healt h a ut h orities, t he s p o ns or's pr oce d ures, or G C P g ui deli nes 
•  I n a de q uat e recr uit me nt of partici pa nt s b y t he I n v esti gat or 
•  Disc o nti n uati o n of f urt her st u d y treat me nt de vel o p me nt  
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 8 3  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
te m p oral se q ue n ce fr o m a d mi nistrati o n of t he test dr u g /st u d y pr oce d ure; ( 2) it c o ul d 
rea dil y ha ve b ee n pr o d uce d b y t he s u bject’s cli nical state, e n vir o n me ntal or t o xic 
fact ors, or ot h er m o des of t hera p y a d mi nistere d t o t he s u bject; ( 3) it d oes n ot f oll o w 
a k n o w n patter n of res p o nse t o t he test dr u g/st u d y pr oce d ure; or ( 4) it d oes n ot 
rea p pear or w orse n w he n t he dr u g/st u d y pr oce d ure is rea d mi nistere d. 
•  
P O S SI B L Y:  T his cate g or y a p plies t o t h ose A Es f or w hic h a c o n necti o n wit h t he test 
dr u g /st u d y pr oce d ure a d mi nistrati o n a p pears u nli kel y b ut ca n n ot be r ule d o ut wit h 
certai nt y. A n A E m a y be c o nsi dere d p ossi bl y relat e d if or w he n it meets 2 of t he 
f oll o wi n g criteria: ( 1) it f oll o ws a reas o n a ble te m p oral se q ue n ce fr o m a d mi nistrati o n 
of t he dr u g /st u d y pr oce d ure; ( 2) it c o ul d n ot rea dil y ha ve bee n pr o d uce d b y t he 
s u bject’s cli nical state, e n vir o n me ntal or t o xic fact ors, or ot her m o des of t h era p y 
a d mi nistere d t o t he s u bject; or ( 3) it f oll o ws a k n o w n patter n of res p o nse t o t he test 
dr u g /st u d y pr oce d ure.  
•  
P R O B A B L Y:  T his cate g or y a p plies t o t h ose A Es t hat t he I n v esti gat or f eels wit h a 
hi g h de gree of certai nt y are rel ate d t o t he test dr u g /st u d y pr oce d ure. A n A E ma y be 
c o nsi dere d pr o ba bl y rel ate d if or w he n it meets 3 of t he f oll o wi n g criteria: ( 1) it 
f oll o ws a reas o n a ble te m p oral se q ue n ce fr o m a d mi nistrati o n of t he dr u g /st ud y 
pr oce d ure; ( 2) it c o ul d n ot be reas o n a bl y e x plai ne d b y t he k n o w n c haracteristics of 
t he s u bject’s cli nical stat e, e n vir o n me ntal or t o xic fact ors, or ot h er m o des of t hera p y 
a d mi nistere d t o t he s u bject; ( 3) it disa p pears or decreas es o n cess ati o n or re d uc ti o n i n 
d ose ( n ote t hat t here are e xce pti o ns w he n a n A E d oes n ot disa p pear u p o n 
disc o nti n uati o n of t he dr u g, yet dr u g -relate d ness clearl y e xists; f or e xa m pl e, as i n 
b o ne marr o w d e pressi o n, fi xe d dr u g er u pti o ns, or tar di ve d ys ki nesia); or ( 4) it 
f oll o ws a kn o w n patter n of res p o nse t o t he test dr u g/st u d y pr oce d ure.  
•  
D E FI NI T E L Y:  T his cate g or y a p plies t o t h ose A Es t hat t he I n v esti gat or feels are 
i nc o ntr o verti bl y relate d t o test dr u g/st u d y pr oce d ure. A n A E ma y b e assi g n e d a n 
attri b uti o n of defi nitel y relate d if o r w h e n it meets all of t he f oll o wi n g criteria: ( 1) it 
f oll o ws a reas o n a ble te m p oral se q ue n ce fr o m a d mi nistrati o n of t he dr u g /st u d y 
pr oce d ure; ( 2) it c o ul d n ot be reas o n a bl y e x plai ne d b y t he k n o w n c haracteristics of 
t he s u bject’s cli nical stat e, e n vir o n me ntal or t o xic fact ors, or ot h er m o des of t hera p y 
a d mi nistere d t o t he s u bject; ( 3) it disa p pears or decreas es o n cess ati o n or re d ucti o n i n 
d ose a n d rec urs wit h re -e x p os ure t o dr u g (if rec h alle n ge occ urs); a n d ( 4) it f oll o ws a 
k n o w n patter n of res p o ns e t o t he  test dr u g /st u d y pr oce d ure. 
 
 
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 8 5  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
•  
I nitial n otificati o n via tel e p h o ne d oes n ot re place t he nee d f or t he I n v esti gat or t o 
c o m plete a n d si g n t he S A E C R F pa ges wit hi n t he desi g nate d re p orti n g ti me fra mes. 
•  
C o ntacts f or S A E re p orti n g ca n be f o u n d i n t he St u d y Ma n ual. 
 
 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 8 6  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
A p pe n di x  5: C o ntr ace pti ve G ui d a nce a n d C ollecti o n of Pre g n a nc y I nf or m ati o n  
Defi niti o ns  
W o m a n of C hil d b e ari n g P ote nti al ( W O C B P)  
A w o ma n is c o nsi dere d fertile f oll o wi n g me narc h e a n d u ntil bec o mi n g p ost -me n o pa usal u nless 
per ma ne ntl y sterile (see bel o w) . 
W o me n i n t he f oll o wi n g c ate g ori es are n ot c o nsi dere d W O C B P  
1.  Pre me narc hal  
2.  Pre me n o pa usal f e male wit h 1 of t he f oll o wi n g:  
•  D oc u me nte d h ysterect o m y  
•  D oc u me nte d bilateral sal pi n gect o m y  
•  D oc u me nte d bilateral o o p h orect o m y  
N ote:  D oc u me ntati o n ca n c o me fr o m t he site pers o n nel’s: re vie w of t he partici pa nt ’s me dical 
rec or ds, me di cal e xa mi nati o n, or me dical hist or y i nter vie w. 
3.  P ost me n o pa usal  fe male 
•  A p ost me n o pa usal state is defi ne d as n o me ns es f or 1 2 m o nt hs wit h o ut a n alter nati ve 
me dical ca us e. A hi g h f ollicle sti m ulati n g h or m o ne ( F S H) l e vel i n t he p ost me n o pa usal 
ra n ge ma y be use d t o c o nfir m a p ost me n o pa usal st ate i n w o me n n ot usi n g h or m o nal 
c o ntrace pti o n or h or m o n al re place me nt t hera p y ( H R T). H o we v er , i n t he a bse nce of 1 2 
m o nt hs of a me n orr hea, a si n gle F S H meas ure me nt is i ns ufficie nt.  
•  Fe males o n H R T a n d w h ose me n o pa usal stat us is i n d o u bt will be re q uire d t o use o ne of 
t he n o n -h or m o nal hi g hl y effecti ve c o ntrace pti o n m et h o ds if t he y wis h t o c o nti n ue t heir 
H R T d uri n g t he st u d y. Ot her wise, t he y m ust disc o nti n ue H R T t o all o w c o nfir mati o n of  
p ost me n o pa usal stat us bef ore st u d y e nr oll me nt. 
C o ntr ace pti o n G ui d a nce  
Male  partici pa nts  
•  Male partici pa nts wit h fe male part ners of c hil d beari n g p ote ntial are eli gi ble t o partici pate if 
t he y a gree t o O N E of t he f oll o wi n g [ d uri n g t he pr ot oc ol-defi ne d ti me fra m e i n Secti o n 6. 1 ]:  
Are a bsti ne nt fr o m pe nile -va gi nal i nterc o urse as t heir us ual a n d preferre d lifest yle (a bsti ne nt o n a 
l o n g ter m a n d persiste nt basis) a n d a gree t o re mai n a bsti ne nt 
•  A gree t o use a male c o n d o m pl us part ner use of a c o ntracepti ve met h o d wit h a fail ure rate of 
< 1 % per year as des cri be d i n T a ble 9             Hi g hl y Effecti ve C o ntrace pti v e Met h o ds 9  
w he n ha vi n g pe nile -v a gi nal i nterc o urse wit h a w o ma n of c hil d beari n g p ote ntial  w h o is n ot 
c urre ntl y pre g na nt  
Me n wit h a pre g n a nt or breastfee di n g part n er m ust a gree t o re mai n a bsti ne nt fr o m pe nile -va gi nal 
i nterc o urse or use a mal e c o n d o m d uri n g eac h e pis o de of pe nile pe n etrati o n d uri n g t he pr ot oc ol-
defi ne d ti me fra me .  
Refrai n fr o m d o n ati n g s per m f or t he d urati o n of t h e st u d y a n d f or 3 0 d a ys  after t he last d ose of 
L T 3 0 0 1 dr u g pr o d uct . 
Fe male p a rtici pa nts 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 8 7  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
Fe male p artici pa nts of c hil d beari n g p ote ntial are eli gi ble t o partici pate if t he y a gree t o use a hi g hl y 
effecti ve met h o d of c o ntrace pti o n c o nsiste ntl y a n d c orrectl y as descri be d i n Ta ble 9             Hi g hl y 
Effecti ve C o ntr ace pti ve Met h o ds 9 . 
T a ble 9             Hi g hl y Effecti ve C o ntr a ce pti ve Met h o ds  
Hi g hl y Effecti ve C o ntr a ce pti ve Met h o ds T h at Are User De pe n de nt
 a  
F ail ure r ate of < 1 % per ye ar w he n use d c o n siste ntly a n d c orrectly.  
 C o m bi ne d (estr o ge n a n d pr o gest o ge n c o ntai ni n g) h or m o nal c o ntrace pti o n ass ociate d wit h 
i n hi biti o n of o v ulati o nb  
•  Oral  
•  I ntr a va gi nal  
•  Tra ns der m al  
 Pr o gest o ge n o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n  
•  Oral  
•  I njecta ble  
Hi g hl y Effecti ve Met h o ds T h at Are User I n de pe n de nt
 a  
I m pla nta bl e pr o gest o ge n o nl y h or m o nal c o ntrace pti o n ass ociate d wit h i n hi biti o n of o v ulati o n b 
•  I ntr a uteri ne de vice (I U D) 
•  I ntr a uteri ne h or m o ne-rel easi n g s yste m (I U S) 
Bilateral t u bal occl usi o n  
Bilateral t u bal li gati o n  
H or m o nal or n o n -h or m o nal I ntra uteri n e de vice (I U D)  
 V asect o mize d p art ner  
A v asect o mize d p art ner is a hi g hly effective c o ntr ace pti o n met h o d pr ovi de d t h at t he p art ner is t he 
s ole m ale sex u al p art ner of t he W O C B P a n d t he a bse nce of s per m h as b ee n c o nfir me d. If n ot, a n 
a d diti o n al hi g hly effective met h o d of c o ntr ace pti o n s h o ul d be u se d.  
 Se x u al a bsti ne nce  
Sex u al a bsti ne nce is c o nsi dere d a hi g hly effective met h o d o nly if defi ne d as refr ai ni n g fr o m 
heter osex u al i nterc o urse d uri n g t he e ntire peri o d of risk ass oci ate d wit h t he st u dy tre at me nt. T he 
reli a bility of sex u al a bsti ne nce n ee ds t o be ev al u ate d i n rel ati o n t o t he d ur ati o n of t he st u dy a n d 
t he preferre d a n d us u al lifestyle of t he p artici p a nt.  
N O T E S:  
a) T y pical use fail ure rat es ma y differ fr o m t h ose w he n use d c o nsiste ntl y a n d c orrectl y. Use s h o ul d 
be c o nsiste nt wit h l ocal r e g ul ati o ns re gar di n g t he use of c o ntrace pti ve met h o ds f or partici pa nts 
partici pati n g i n cli nical st u dies.  
b) H or m o nal c o ntrace pti o n ma y be s usce pti ble t o i nteracti o n wit h t he st u d y treat me nt, w hic h ma y 
re d uce t h e efficac y of t he c o ntrace pti ve met h o d. I n t his case, t w o hi g hl y effecti ve met h o ds of 
c o ntrace pti o n s h o ul d be utilize d d uri n g t he treat m e nt peri o d a n d f or at 3 0 d a ys  after t he last d ose 
of st u d y treat me nt  
 
Pre g na nc y T esti n g  
•  
W O C B P s h o ul d o nl y be i ncl u de d after a c o nfir me d me nstr ual peri o d a n d a ne gati ve hi g hl y 
se nsiti ve ser u m pre g na n c y test . 

C O N FI D E N TI A L  
  
L u m osa T hera pe utics C o., Lt d.  
Pr ot oc ol  L T 3 0 0 1 -1 0 5  
Pa ge 8 8  of 8 8  
 
Stat us: V 1. 4; Date 1 1 Mar 2 0 2 1  
•  
Pre g na nc y testi n g will be perf or me d w he ne ver a me nstr ual c ycle  is misse d or w he n pre g na nc y is 
ot her wise s us pect e d  
C ollecti o n of Pre g n a nc y I nf or m ati o n  
M ale p artici p a nt s wit h p art ners w h o bec o me pre g n a nt  
•  
T he I n vesti gat or will atte m pt t o c ollect pre g na n c y i nf or mati o n o n a n y mal e partici pa nt’s fe male 
part ner w h o bec o m es pre g na nt w hile t he m ale p artici pa nt is i n t his st u d y. T his a p plies o nl y t o 
male partici pa nts w h o recei ve L T 3 0 0 1 dr u g pr o d uct . 
•  
After o btai ni n g t he necessar y s i g ne d i nf or me d c o nse nt fr o m t he pre g na nt fe male part ner directl y, 
t he I n vesti gat or will rec or d pre g n a nc y i nf or mati o n o n t he a p pr o priate f or m a n d s u b mit it t o t he 
s p o ns or wit hi n 2 4 h o urs of lear ni n g of t he p art ner’s pre g n a nc y. T he fe mal e part ner will als o b e 
f oll o we d t o deter mi ne t h e o utc o me of t he pre g na n c y. I nf or mati o n o n t he st at us of t he m ot her a n d 
c hil d will be f or war de d t o t he s p o ns or. Ge n erall y, t he f oll o w -u p will be n o l o n ger t ha n 6 t o 
8  wee ks f oll o wi n g t he esti mate d deli ver y date. A n y ter mi nati o n of  t he pre g na nc y will b e re p orte d 
re gar dl ess of fet al stat us ( prese n ce or a bse nce of a n o malies) or i n dicati o n f or t he pr oce d ure.  
Fe m ale P artici p a nts w h o bec o me pre g n a nt  
•  
T he I n vesti gat or will c ollect pre g na nc y i nf or mati o n o n a n y fe male parti ci pa nt w h o bec o mes 
pre g na nt w hile p artici pati n g i n t his st u d y. I nf or m ati o n will be rec or de d o n t he a p pr o priat e f or m 
a n d s u b mitte d t o t he s p o ns or wit hi n 2 4 h o urs of lear ni n g of a partici pa nt's pre g na n c y.  T he 
partici pa nt will be f oll o we d t o deter mi ne t he o utc o me of t he pre g na nc y. T he I n vesti gat or will 
c ollect f oll o w -u p i nf or m ati o n o n t he partici pa nt a n d t he ne o nate a n d t he i nf or mati o n will be 
f or war de d t o t h e s p o ns or. Ge nerall y, f oll o w-u p will n ot be re q ui re d f or l o n ger t ha n 6 t o 8 wee ks 
be y o n d t he esti mate d deli ver y date. A n y ter mi nati o n of pre g na nc y will be re p orte d, re g ar dless of 
fetal stat us ( pres e nce or a bse nce of a n o malies) or i n dicati o n f or t he pr oce d ure. 
•  
W hile pre g n a nc y itself is n ot c o nsi dere d t o b e a n A E or S A E, a n y pre g na nc y c o m plicati o n or 
electi ve t er mi nati o n of a pre g na nc y will be re p orte d as a n A E or S A E. A s p o nta ne o us a b orti o n is 
al wa ys c o nsi dere d t o b e a n S A E a n d will b e re p orte d as s uc h. A n y p ost -st u d y pre g n a nc y-relate d 
S A E c o nsi dere d reas o na bl y relate d t o t he st u d y treat me nt b y t h e I n v esti gat or will be re p orte d t o 
t he s p o ns or as descri be d i n Secti o n 9. 1 . W hile t h e I n vesti gat or is n ot o bli gate d t o acti vel y see k 
t his i nf or mati o n i n f or mer st u d y partici pa nts, he or s he ma y lear n of a n S A E t hr o u g h s p o nta ne o us 
re p orti n g.  
•  
A n y fe male p artici pa nt w h o bec o mes pre g na nt w hile partici pati n g i n t he st u d y will be 
wit h dra w n fr o m t he st u d y .