Exhibit 10.1

E X E C U T I O N V E R S I O N M A S T E R S E R V I C E A G R EE M E N T N E O N C TE C H N O L OG I E S H O L D I N G S , I N C . A N D I N S I GH T S PH A R M A C E U T I C A L R E S E A R C H LL C 1 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N M A S T E R S E R V I C E S A GR E E M E N T T his M a s t e r S e r v i ce s A gr e e m e nt ( h e r ei n a ft e r Ag r e e m e n t E ff ec t i v e D a te 4 October 2025 , (hereinafter (1) N E O N C T E CH N O L O G I E S HO L D I N G S, I N C . , a c om p a n y r e gi s t e red o n t h e N a s d a q s t o c k e x ch a n g e w it h i t s p ri n c i p al pl a c e o f bu s i n e s s a t 2 3 9 7 5 P a r k S o r r e n t o, Suite 2 0 5 , C a l a b a s a s , C A 9 1 3 0 2 , Un i t ed S t a te s ( h e r e i n a f t e r C LI E N T ; - a n d - (2) I N S I G H T S PH A R M A C E U TI C A L R E S E A R C H L L C , a l imi t ed l i a bi l i ty c om p a n y i n c o r po r a te d i n th e Un i t ed A r a b Emira t e s w it h i t s p r i n c i p a l pl a c e o f b u s in e s s at a t B u i l di ng of M a s d a r M 13 T L i mi t e d, S E 4 5 _ 0 5 , P lot C 16 , Kh ali f a C i t y, A bu D h a bi , U nite d A r a b E m ir a t e s I R O S . I R OS a n d C L I EN T P a r t y P a r t i e s 2 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G C O N T R A C T P AR T I CU L A R S U A E T er r i t o r y T h r e e ( 3 ) y e a r s f r o m the e f f e c t ive d a te of t h e f i r st W o r k O r d e r e x e c u t e d u n d e r t h i s A g r e e m e n t . I n i t i a l T e r m C L I E N T : N a m e : A m ir H e s hm a t p o u r T e l e p h o n e : + 1 - 310 - 7 2 1 - 43 91 E m a i l: a m i r @ n e o n c . c o m I R O S : N a m e : I s l a m E l t a n t a w a y T e l e p h o n e : + 9 7 1 5 45 3 5 3 5 51 E m a i l: is l a m . e lt a n t aw y @ i r os. a i R e l at i o ns h i p Ma n a ge r A M u l t i - S i t e , R a n do mi ze d , P h a s e 2 b / 3 S t u dy E va l u a t i ng O v er a l l S u r v i v a l (O S ) o f I n t r a n a s a l N E O 1 00 in P a t i e n t s w i t h P r o g r e s s ive o r R ec ur r e n t G r a de I I I A st r o c y t o m a s a n d G l i o b l a s t o m a M u lt i f o r m e (G BM ) , S t r a t i f i e d by ID H 1 M u t a t i o n S t a t u s , C o m p ar e d t o B e s t S t a nd ar d o f C a r e T i t l e o f f i r st S t u dy un d e r f i r s t WO F o r C L I E NT : A d d r e s s : 2 3 9 75 P a r k S o r re n t o , S u i t e 205, C a l a b a s a s, CA 9 1 30 2, U nit e d S t a t e s E m a i l: jn e m a n @ n e o n c . c o m A t t e n t io n : J o sh N e m a n , P h D F o r I R O S : A d d r e s s : M B ZUA I c a mpus i n M a s d a r C i t y , G r ou n d L e v e l, O f f i c e U nit G 19 , I n c ub a t o r B u i l d i ng , M a sd a r P O B O X 1 127 7 8, A b u Dh a bi, Un it e d A r a b E m i r a t e s E m a i l: i s l a m. e l t a n t a w y @ i ro s . a i , w i th a c opy to l e g a l @ m 4 2 . a e A t t e n t io n : I sl a m E l t a n t a w a y A d d r e ss F o r N o t i ce s

E X E C U T I O N V E R S I O N WH E R E A S A. I R OS i s a Co n t r ac t R e s e a r c h O r g a n i z a t ion ( CR O ) p r o v i d i ng c l i n i c a l r e s e a r c h s e r v i ce s. B. C L I EN T i s a c lin i c a l - s t a ge lif e s c i e n c e s c o m p an y f o c u s e d on t h e d e v e l o p m e n t a n d c omm e r c i al i za t i o n of ce nt r a l n e r v o u s s y s te m th e r a p e u t i c s t h at a r e d e s i g n e d t o ad dr e s s t he p e r s i s t e n t c h a l l en g e s i n o v e r c o mi n g t he bl o o d - br ai n b a r r i e r a nd ac t s a s t h e s p o n sor o f c e r t a i n c l i n i c a l tr i a l s in the T e r ri to r y . C. The P a rt i e s d e s i r e t o e n te r i n t o t h i s A g r ee m e nt t o p r o vi de t he t e r m s a n d condit i o n s u p o n w h i ch C L I EN T m ay en g a g e I R O S, fr o m t i me t o t i m e , t o p r o v i de C R O s e r v i c e s f o r t he m an a g e m e n t of c l i n ic a l d r u g s t ud y (i e s ) s p onsored b y C L I EN T u n d er t his A g r ee m e n t ( ea c h a S t u d y S t u d i e s ) by e x e c ut i n g a WO ( a s d e f i n e d b e l o w) s p e c i f y i n g t h e d e t a i l s o f t h e s er v i ce s a n d t he re l a t e d te r m s a n d condi t i o n s . N O W, T H E R E F O R E , t he P a r t i e s agre e a s f o l l o w s : 1 . D E F INI T I O N S 1 . 1 T his Agr e e m e n t s h all b e i n t e rp ret ed i n a c c o r d a n c e w i t h t he pro vi s i o ns on i n t e rp r e tat i on s e t out i n S c h e d u l e 1 (D e f i n i t i o n s & I n t e r p r e t a t i o n ) a n d ca p i t a l i zed w o rd s s h a ll h a v e t h e m e a n ing g i v e n t o th e m i n S c h e d u l e 1 ( D e f i n i t i o n s & I n t e r p r et at i o n ), unle s s t h e c o nt e x t r e q u i r e s ot h e r w i s e . 2 . S E R V I C E S . 2 . 1 S c o p e o f A g r e e m e n t . P ar t i e s t o c o n t r ac t f or mul t iple S t u d i e s th r o ugh t he i s s u a n c e o f mult i p l e W O s ( a s d e f i n e d b e l o w ) , w i t h o u t h a vi ng t o r e - n e g otiate t he b a s ic t e r m s and co n dit i o ns c o n t a i n e d h e r e i n . T h i s A g r e e m e n t co v e r s t he p r o v i s i on o f C R O s e r v i ce s b y I R O S t o C L I E N T a n d , a c co r di ng l y , thi s Ag r e e m e n t r e pre s e nts a v e hi c l e b y w h ic h C L I EN T can e f f i c i e n t l y co n t r a c t w i t h I R OS f o r C R O s e r v i ce s . 2 . 2 W o r k O r d e r s . T he s p e c i fic d e t a i l s of t he S e r v i c e s to b e p e r f o r m ed b y I R OS f o r ea c h S t u d y s h all be s epar a t e l y n e g o t i a t ed a n d s p ecifi ed in wr i t i ng on t e r m s a nd i n a fo r m a cce pt a ble t o the P a r ti e s ( ea c h s u c h WO , a f o r m of w hi ch i s a t t a c h e d a s S c h e du le 2 ( W or k O r d e r ) . Ea c h W O w i l l s e t o u t a s ap p ro pr i a t e , t he n a t u r e a n d s c o pe of w o r k, S t u dy - s p e c i f ic a ss u mpti on s , the s c h ed u l e of w ork t o b e p e r f o r m e d or S e r v i c e s t o be p rov id e d d u r i n g t h e c o ur s e of a S t u d y, t he I R O S P e r s o n n el, t he b u d g e t, th e r e le v a nt P r ot o c o l a n d t he p aym e nt s ch ed ul e, o r g a ni za t i on of f o l lo w - up a c t iv i tie s a n d /or , a s a pp l i c a b le, any o t h e r t e r m s r e qu i r ed f o r t he p e rfo r m a n c e o f t h e S e r vi c e s . W h e n a p pli c a b l e , e a c h WO s h a l l c o nt a i n a l i s t o f o b l i g a t i ons a n d r e s p o ns i bil i tie s b e i n g d e le g a t e d to I R OS i n c o nj u n c t i on w it h the r e le v a nt W O . On c e e x e c u t ed b y e a c h P a r t y, each WO s h a l l be s u bj e c t t o a ll o f t h e t e r m s and c o n d i t i o n s of th i s Ag r ee m e n t, i n a ddi ti on t o t h e s p e c ific d e tail s s et for t h i n t he W O . T o t he e x te n t a ny t e r m s or p ro vis i o ns of a W O co nf l i c t w i t h t he t er m s a n d p r o vi s i ons of thi s A g r ee m e nt , t h e ter m s and p r ov i s i o n s of t h i s Ag r ee m e n t s h a l l p r e v a i l , e x ce p t t o t h e e x t e nt t h at t he a p pl i c a b l e W O ex p r e s s l y a n d s p e c i fic a l l y s t a te s an inte n t t o s u per s e d e the A gr ee m e n t o n a s p e c ific m a t t er . 2 . 3 A W O s h all c o m m en ce a s of t he c omm e n ce m e nt d a t e, s e t f o rt h i n t h a t W O a n d s h a l l r e m a i n in for c e u nt i l t he c o mp l e t i o n of the S tudy or t h e ap p l i c a b le S e r vi c e s, unle s s t e r mi n a t ed e a rlie r a s pr o v i d e d f or i n Cl a u s e 2 6 . 2 . 4 E a ch WO s h a ll s t and al o ne w it h r esp e c t t o a ny o t h e r WO e n t e r e d und e r th i s Ag r e e m e nt . T he p e r fo r m a n c e of o bli g a tio n s u n d er a ny o n e W O sh a ll n ot a f f e c t, and s h a l l at a l l t im e s be u n r e l a t ed t o , the p er f or m a n c e of a n y o t h e r W O e n t e r ed i n t o u n d e r t his Agr e e m e n t . The e xpira t ion or ea rl y t e r m i n a t i o n of o n e WO s h a l l n o t ( u n l e s s e x p r e s s l y a gr e e d ot h e r w i s e by the P a rt i e s) im p a c t a n y o th e r W O , wh i ch s h all r e m a in i n f u ll f o r c e and e f f e ct . 2 . 5 N a t u r e of S e r v ic e s . T h e s er vi c e s c o v e r e d b y thi s A gr ee m e nt m ay i n c lu d e s t r a t e gic p lan n i n g, ex p ert co n s ultati on, c l i ni c a l t r i a l s e r vi c e s, r e g u l a to r y , p r oj e ct m a n a g em e n t and o t h e r r e s e ar c h a n d d ev el o p m e nt s e rv i ce s r eq u e s t e d b y C L I EN T and a g r ee d t o b y I R OS a s s et f o rt h i n t he r e l e v a n t W O( c o l l ecti v e l y, t he S e r vi c e s I R OS s h all r ep o r t on the p r o g r e ss o f e ach S t udy t o C L I EN T on a m o n th ly b a s i s or m o r e f re q u e n t l y w h e r e a g r eed i n a W O . I R O S r easo n a b le r equ e s t. 3 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N 2 . 6 C lie nt ' s A ut h o r i z a t i o n . A ny re s p o ns i b il i t i e s n o t e x p l i c it l y tr an s fe rred t o I R OS un d e r a s i g ned W O s ha ll r e m a i n t h e le ga l a nd r egu lat o r y r e s p o n s i b i l i t ie s of C l i en t . E xcep t a s o t h er w i s e a g r eed b y t h e P a rt i e s i n wr i t ing, Cli e nt is a nd a t a ll t i m e s r e m a i n s, i n a l l g e o gr a ph i c a l r e gi o n s w h e r e a S t u dy is b e ing p e rf o r m e d, 2 . 7 Cha n g e O r d e r s . 2.7 . 1 An y m a t er i a l chang e i n t h e de t a i l s o f a W O or t h e a s s u m p t ions s p e c if i e d i n t h e W O upon w h ic h the W O i s b a s e d ( i n c l u din g , but n ot l im i t e d t o , c h a n g e s i n a n a gr e e d s t ar ting d a te f or a S t u dy o r s u s p e n s i on of t h e S t udy by CL I EN T ) m ay r eq u i r e cha n ge s i n t h e b u d g e t an d / or t i m e l i n e s , and s h a l l r equ ir e a wr i t t en a m e n d m e n t t o th e W O i n t h e f orm o f a c h a n g e or de r ( ea c h , C O O s h a ll de t a i l t h e r e q ue s te d c han g e s to t h e a p p l i cab le ta s k, r e s p on s i b i li t y , d ut y, b udg e t, t i m e line a nd o t h e r m a t t e r s . Th e C O w ill b e come ef f ec t i ve upon t h e e x ecu t i on of th e C O by b o t h P a r t i e s (u n le ss s o m e ot h e r e f f ec t i v e da te i s s e t o u t i n w r i t i n g in the C O) , a nd I R O S s h a ll u s e rea s on abl e e ff o r ts to i m pl e m e n t the c h an g e s a s s o on a s i s r easo n a b l y p ra c tic a b l e . B o th P a rt i e s a g r e e to a c t i n go o d f a i t h and p r o m pt l y wh e n co n s i de ri ng a C O reque s te d by t h e o t h e r P a r t y . W i t h ou t l im it i ng t h e f o r eg o i n g : ( a ) CL I E N T ag r ee s t h a t it w i l l no t u n r e a s o nab l y w it hh o l d a pprova l of a C O , e ven i f it i n v o l v e s a f i x e d p r i c e c o n t r a c t , i f t h e p r o p o s ed c h a n g e s i n b u d g e t s or t i m e li ne s r e s u lt f rom m a t e r i a l ch a n ge s i n t h e a s s u m p ti ons u p o n wh i c h t h e i n i t i a l bud g et or t im eli ne s w e r e ba s e d, i n cl u d in g , bu t no t l i m i t e d t o, t h e a s s u m p t i o ns s et f or t h in t h e b u d g e t or t i m e l i n e s ; and ( b) I R OS ag r ee s t h at i t n o t h a v e t h e c a p a b i l i t y t o i m p le m e n t t h e change ; ( i i ) t h e c ha n g e wo uld pl ac e I R O S i n b r ea c h of l a w ; o r ( i i i ) th e pa rt i e s a r e u nab le t o a g r e e o n t h e b u d g e t and o t h e r c o m m e r c i al te r m s of t h e C O . 2.7 . 2 Su b ject t o Cla u se 2.7 . 3 , I R O S s ha l l n o t p e r f o r m o u t - o f - s cop e S e r v ic e s in t h e ab s e n c e of a n execu t ed C O . I R O S r e s e rv e s t h e ri gh t t o p o s tp o n e e f f ec t i ng m a t er i a l chan g e s i n th e S t u d y s co p e un t i l s u c h ti me a s th e P a r tie s a g re e t o a n d exe c u t e t h e c orr e s pond i ng C O , p r o vided t ha t any r ea s o n a b le c os t s in c u r r ed i n s o d o i n g a r e born e b y I R OS and a n y d e a d li ne s s p e c ifi ed can s t i l l b e m e t . For a n y C O t ha t af f ec t s t h e s c o p e of t h e re g u l a t or y o b l i gat i o ns t h at h a v e be e n t r a ns f e r re d t o I R O S , I R O S and C L I E N T s h all ex e cu te a co r r e s po n d i ng a m e n dm e n t to th e w r i t t e n transfe r of o b li ga t i ons s et o u t i n t h e a p p l i c a b le W O . 2.7 . 3 I R OS m u s t de v i a te f rom Cl a u s e s 2 . 7 i f a mo d i f i c a t ion r ea s o n a b ly in v o l ve s t h e s a f e t y of a h um an s u b je c t or t h e i n t e grit y of t h e S t u dy d at a , i n w h i ch c a se I R OS s h a l l q u i ck l y ac t o n th e r eq u e s te d ch a n ge , and w hen p r a c tica b l e , g i v e n o t i c e pro mp t l y t o CLIE N T by tel ep h o n e or e l ec tr o n i c c o m mu n i c a t io n t h a t such s c op e c h a n g e occ u r re d an d a C O m ay b e r e q u i r e d . CLIE N T a n d I R O S w i l l w o r k i n g ood f a i t h t o p r om p t l y e x e c u te t h e r e l eva n t C O . 3 . P E R S O NN EL 3 . 1 E ac h P a rt y s h a l l a p p o i n t : 3.1 . 1 a r e lati o n s h i p m ana g e r i n r e s p e c t o f t hi s A g r ee m ent , w ho sh a l l b e na m ed i n t h e Con tra c t P a r t i c u l a r s ; a n d 3.1 . 2 a p r o j ec t re p re s e n t a t iv e m a nage r f o r ea c h W O , w h ic h per s o n w i l l b e i d e n t ifi ed i n t h e ap p l i c a b le W O . T h e r e lati o n sh i p m an a g e r and t h e W O p r o ject r ep r e s e n t a t i v e , h o w e v e r, s h all n o t hav e a u t h o rit y t o co n t r a c t ua l l y b in d th e P a r t i e s i n t e r m s o f s i g n i n g a n y v a r i at i on t o t h i s Ag r e e m e n t or a ny W O o r C O . I R OS sha ll u s e re asona b l e e n d e a v o ur s t o en s ur e t h a t t h e s ame pe r s o ns ac t a s t h e I R O S r e l a t i o ns h i p m ana g e r and a s W O pro j e c t r e p r e s e n t a t i v e s t h r ou g h o u t t h e t e r m of t h i s A gr ee m en t o r t h e r e l e v a n t W Os, b u t m a y r e p l a c e s u c h pe r s o n s f rom t ime t o t i me w her e r ea s o n a bly nec e ss a r y in t h e i n t e r e s t s o f I R O S' b u s i ne s s . 4 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N 3 . 2 I R OS r ep r e s e n t s , w a r r an t s and u n d e rt a k e s t ha t: 3.2 . 1 i t s h all us e pe r s on n e l ( in c lud i n g w i t h o u t l imi t a ti on i nd e p e n d e n t con tr ac t o r s , c o n s u l t a nt s , e m p l o y e e s and a ge n t s ) a s i t dee m s nec e ss a r y t o p e r f o r m t h e S e r v i ce s t o t h e r e q u i s i t e s ta nd a r ds ( the I R O S P e r s o n n el w h o a r e a pp ro pr i a te ly tra in e d, qu a l i f i e d b y e d uc ati o n a n d e x p e r i en c e d t o p e r for m I R O S 's o bl i g atio n s un de r t his Ag r e e m ent . I R O S s h all be re s p o nsible f o r mo n i to r i ng t h e p e rfo r m a n c e o f s u ch pe r s onne l w ho a r e en g a ged i n t h e p erf or m anc e o f S e r v i c e s ; 3 .2 . 2 t he I R O S P e r s o nn e l h av e, a nd a t a l l t i m e s d u r i n g t he te rm of this A g r e e m e n t sh a l l h a v e , ap p ro pr i a t e l i c en s e s, approv a l s a nd c e r t i fi c atio n s nece s s a r y t o s a f e l y , a d e q u at e l y a nd la w f u l ly pe r fo r m t he i r o b l i ga t i o ns u nd e r th i s Ag re e m e n t and a n y W O ; and 3.2 . 3 I R OS s h all b e r e s p o n s i b l e f o r m o n it o r i n g t h e p e r f o r m a n c e a nd c o m p lia n c e w it h A pp li c a b l e L a w s of s u ch I R OS P e r s o nne l w ho a r e e n g ag e d in t h e p e r f o r m a n c e of S er v ic e s . 3 . 3 I R OS w i ll b e s o l e l y re s p o n s i b le f o r t h e w age s /f e e s and e m p l o ym en t r e lat ed lia b i l i t i e s a s s o c i a t ed w i th t h e e mplo y m e nt o f a ny I R O S P e rs o nn el wo r k i ng on the WOs . 4 . D E B A R M E N T 4 . 1 E ac h P a r t y r e pr e s en t s , w a r r a nt s a n d u n de rt ake s t ha t ne it he r i t n or any o f i t s r e s pec t i v e p e r s on n e l t ha t i t en g a g e s w h o ar e t o p e r f o r m any of it s ac t i v it i e s i n c o nn ecti on w i t h t h i s A gr ee m e n t ha v e b e e n ( i ) p r o h i b i t ed f r om p ro v i d i ng m e d ic a l o r cli n ic a l r e s ea r c h s e r v i c e s o r d eb arr ed by any G ove r n m en t a l Ent i t y of any k i nd i n a n y j u ri sd i c t i on or ( i i ) c onvi c t ed o f a c r ime for w h i c h a p e rson c a n b e proh i b it ed f ro m p r o v i d i n g m e dic a l or c l i n i ca l r e s e a r ch s e r v i c e s or d e ba r r e d i n a ny j ur i s di c t io n . 4 . 2 E ac h P a r t y al s o re pr e s e n t s , w arr a n t s and u n d e r t a k e s t ha t n eit he r it nor any of i t s r e s p ecti v e e m p l oye e s h a v e b e en (i ) t hr e a t en e d to b e d e b a r re d o r o t he r w i s e p r oh i bi t e d f ro m p r ov i d i ng m e d i c al o r c l i n i c al r e s e a rch s e r v i ce s b y any Go v er nm ent al E n ti t y of a n y k i n d i n a n y j u ri sd i c t i o n , or ( i i ) in d i c t ed f o r a c ri m e or o t he rw i se en g a g ed i n c o n d u ct fo r w h i ch a pe r s on can b e p ro h i b i t ed f r o m p r o v i d i ng m e d i ca l o r c l i nic a l r e s e a rch s e r v i ce s o r d e ba r re d u n de r a ny A p p l i ca b l e L a w s or r e g u l a t i on i n a ny j u ri sd i c t i on r e g u l a t i ng t h e pe r f o r m a n c e of S e r v i ce s re l a t i n g t o p h a r m a c e u t i c a l p r o d uc t s o r c l i n ical s tud i e s . 5 . A N T I - B R I B E R Y A N D A N TI - C O RR U P T I O N . 5 . 1 I n c ar r y i ng o u t i t s r e sp o ns i b i l i ti e s u n d e r t h i s A g r ee m e n t, n ei t he r P a rt y n o r a ny of i t s r e s pe c t i v e off i c er s, e m p l o y e e s , su b - co n t r a c t o r s , r e pr e s e n t a t i v e s or a g e n t s w ill p a y , o f f e r o r p r o m i s e t o p a y, or a uth o riz e t h e pa ym e n t o f, a ny m o n e y, o r g i v e or p r om i s e t o g i v e, o r a u t hor i z e t h e giv i ng o f, any s e r v ic e s o r a n y t h i ng e l s e of v a lu e , e i the r d ir ec t l y or t h r o u gh a t h i rd par t y, t o a ny o ff ic i a l o r e m p l o ye e o f a n y G o v e r n m e n t a l E n ti t y , or of any a g e n c y o r s u b d i v i s ion t he r e o f , or to a n y p o li t ic a l par t y or o f f i c ial t h e r e o f o r t o any cand i da te f o r p o l it i ca l off i c e c o r ru p t l y for t h e p u r p o s e of i m p r o pe r l y (i ) i nf l uenc i ng a ny a c t or d e c i s i on of t ha t person i n h i s off i c ia l c a p a c i t y, i nc l u d i ng a d e c i s i on t o f a il t o pe r fo r m h i s of fi c i a l f u nc t i o ns w i t h s u c h G o v e r n m e n t a l E n ti t y or su c h p o li t ic a l pa rt y, ( i i ) i n d u c i ng such pe r s o n t o us e h i s i nf l u e n c e w i t h s u ch G o v e r n m e n t a l En ti t y or su c h p o l it i ca l pa rt y t o a f f ect o r infl ue n c e a n y ac t o r d e c i s ion t h e r e o f , or ( ii i ) s ecur i ng a n y i m p r o p e r a d van t ag e . Ea c h P a r t y s h a ll r e p or t a n y vio l a t i on of i t s ob l ig a t i o ns u n de r Cl aus e 5 . 1 p r o mp t l y t o t h e o t he r P a r t y . 6 . C O OP E R A T I O N ; D I S C L O SU R E OF H A Z A R D S . 6 . 1 CLIE N T s h all f o r w ard t o I R O S i n a t i m e l y m a n n e r a ll d o c u m e n t s , m a t er i a l s a n d i n f or m a t i o n i n CL I EN T p o s s e s s i on or c o nt r o l r ea s o n a b l y n e ce s s a r y f or I R OS t o c o n d u ct t h e S e r v ic e s . CLIE N T s h a l l p r o v i d e I R OS w i t h a l l in f orm a t i on a v a i l ab le t o it r e g a r d i ng kno w n or p o t en tial haza r ds a s s o ci a t e d w it h t h e u s e of any su b s t a n c e s , i nc l u d i n g a n y S tudy D rug, or e q u i p m e n t s u ppl i ed t o I R OS or t o a n y S t u d y s i t e by CLIE N T , and CLIE N T s h a l l co m p l y w it h all A p p lica b l e La w s co n c e r n i ng t h e s h i p m e n t o f s u c h s u b s t ance s . 5 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N 6 . 2 CLIE N T sh a l l : 6.2 . 1 de l ive r a l l S tu d y D r u g s , e q u i p m en t or o t h e r c l i n i c a l s u p p lie s t ha t m ay b e r e q u i r e d f or a S t u d y and wh i ch C L I E N T ha s a g r e ed t o p r o v i d e p ur s ua n t to a Cl i n i c a l T ri a l A gr e e m e n t ( t h e ) t o e ach r e l evan t I ns t i t u ti on t i m e o us l y . 6.2 . 2 u s e a l l r easo n a b le e ff o rt s t o s u pp l y s u f f i c i e n t q u a n t i t i e s of t h e a p p lic ab le S tu d y S u p p l i e s a s n ece s s a ry t o c o n d uc t t h e S t udy s e t f or t h i n t h e W O . A ll ne ce s s a ry a p p r o v al s for th e im p o r t a ti on of s u c h d ru g s or e q u i p m en t in t o t h e Ter ritor y s h a ll b e o b tai n e d by C L I E N T ( a t i t s e x p e n s e) . 6 . 3 I n no e v e n t s h a l l any S t udy S u pp lie s b e u s ed by I R OS f o r a n y p u r pos e o t he r t h a n a s e xp r e s s l y s et f o r t h i n t h e a p pl i c abl e P r o t o c o l. 6 . 4 W ithin 6 0 ( s ixty) d a ys a f t e r t he c o m p le tion of a S t udy, I R O S w ill p r o vi de to CL I E N T a w r i t te n a c co u n t i n g of all cli n i c al s u pp lie s s u pp li ed by CLIE N T t o I R O S t o m a nag e w it h t h e I n s t it u t i o n ( s ) a s p a r t of t h e S t u d y S u p p l i e s . I R OS w ill u s e a l l r e a s onab le e f f o rt s t o r e t u r n or proc u r e t h e r e t u r n, of a l l u n used S tu d y S u p p l ie s p r o v i d e d by CLIE N T t o In s t i t u tio ns i n ac c o r da n c e w i th r e q ui r e m en t s i n th e a p p l i c a b le Cl i n i ca l T r i a l Agr ee m en t o r a s oth er wise inst r u ct e d b y CL I E N T . D ur i n g ea c h S t u dy, I R O S w ill p r ocu r e tha t t h e In s t i tu ti ons and I n v e s t i g at o r s m a i n t a in r eco r d s o f (i ) t h e d at e s a n d a mo u n t s of a l l S t u d y S u p p l i e s r ec ei v e d by I nve s t i g a t o r s ; ( i i ) t h e da te s, a m oun t s a nd s u b j ec t s t o w h om S tu d y D r ugs h a v e been d i s p e n s ed ; (i i i ) th e da t e s and a m o u n t of S t udy D r u gs s p i l l e d o r lo s t ; and ( i v ) th e da t e s and a m ou n t s of S tu d y Dr u gs be i ng re t u r n e d or d e s t ro y e d . 7 . D E L A Y S A N D E X TE N S I O N O F TI M E L I N E S . 7 . 1 I R OS i s n o t ac c o u n ta b le f or d el ays i n th e pe rf o r m a nc e of it s o b l i ga t i o ns un d e r t h i s A g r e e m en t or u n d e r a W O t o t h e e x te n t t ha t s u c h de l a y i s d u e s o l e l y to (i ) t h e a c tio n s , e r r or s o r o mi s s i o n s of a n y G o v e r n m e n t a l E n ti t y ; ( i i ) r e g u l a t o r y or ex t e r n al e t h ic s c o m m i tte e e nc u m br a n c e ; ( i i i ) S t udy e n r o l m e n t f or cli n ic a l s t ud i e s a t t h e S i t e s i f I R OS can p r o v i d e w ri t t e n ev i d e n c e t ha t i t ha s f u l l y p e r f o r m e d i t s S e r v i ce s r e l a t ed t o co n t ac t i n g a n d m a in t a i n i ng c o n t ac t w i t h I n s t i t ut i on s ; ( i v ) a s a c o n s equenc e of F or c e M a j eu r e ; o r ( v ) a s a r e s u l t o f any d el ay o r f a i l ur e by t h e C L I E N T t o pe rf or m a n y o f i t s o bl i ga t i o n s u n d e r t h i s Ag re e m e n t or any Cl i n i ca l Tr i a l A g r ee m e n t ac t i o n s or o mis s i o ns o f C L I E N T or a n y oth e r d i r e c t o r in d i r ec t c on t ro l, i nclu d i ng cha n ge s i n P r o t oc o l r e que s te d by I n v e s t i g at or s , R eg u l at o ry A u t h o r i t i e s , ex t e r n al e t h ic s c om m i t t e e s or f a i l u r e of CLIE N T t o t i m e l y p r ov i d e d o c u m e n t s, m a t e ri a l s o r i n f o r m a t i on or to o t h e r w i s e c o o p e r a te w i t h I R OS wh er e t h i s i s r easo n ab l y req u i r e d f o r I R OS t o t i m e l y a n d p r ope rl y p e r f or m t h e S e rv ice s i n ac c o r da n c e w it h th e t im e l i n e s d e s c r i b e d i n t h e a p p l i cab le W O . I n t h e eve n t o f a n y d e l ay a s co n t e m p l at e d u n de r t h i s Cl a u se 7 . 1 , I R OS sh all p r o v i d e n o t i c e t o C L IE N T a s s oon a s r e a sona b l y pr a c ti c a b le a n d u s e co mm e r ci a l ly r ea s o n a b le e f f or t s t o c o nt i n u e p e r f orm an c e of t h e S e rv i c e s n o t a f f ec t ed by s u c h d el ay i n ac c o r da n c e w it h t h i s A g r ee m e n t . 7 . 2 I n t h e e v e n t I R OS i s u na b l e t o co mp ly w it h i t s o b l ig a t i o n t o m e et any t i m el i n e s s e t ou t in a W O or Cli n ic a l T rial Ag r e e m e n t d u e s o l e l y t o CLIE N T f a i l u r e to p e r fo r m it s o b l i g ati o n s un d e r t h i s Ag re e m e n t or any C l i n i c a l T r i a l Ag r ee m e n t or i s d e l a y e d i n s u c h p er fo r m an c e , t h e t i m e l i n e s s e t o u t i n t h e W O s h all b e m o d i f i ed a s de s c r ib e d i n C l a us e 2 . 5 ( Chang e O rde r ) a n d ex t en d e d by t h e l eng t h of t h e d el a y , u n l e s s CLIE N T ag r ee s i n w ri t i ng t o pa y a n y a ddi t i o n a l c o s t s t h at w o u l d b e r e q u i r e d t o m ee t t h e or i g i na l tim e l i ne . I n a d d it i o n , C L I E N T w i ll p a y a l l n o n - cance l ab le cos t s and e x p e n s e s i ncu r r e d b y I R OS in ac c o r d a n c e w i t h t h e r e l e v a n t W O and any no n - can c e l ab le c os t s and ex p e n s e s i ncu r r ed by Su b c o n tra c to r s t ha t w i l l b e pa s s ed t h ro ugh t o I R O S, d u e t o s u c h de la y . I R OS s h all us e r ea s o nabl e e f f o r t s t o m i ti ga t e a n y lo s s e s a ri s i ng p u r s u a n t t o t h i s p a r a gr a p h . 7 . 3 S u bj e c t t o C l a u s e s 7 . 1 a nd 7 . 2, I R OS a ckn o w l e d g e s th at it sh all p r o v i d e th e S e r vi ce s i n ac c o r d a n c e w it h t h e de a dl i n e s spe cif i e d i n t h e W O or C O(s ) , or a s m a y b e su b s e q u e n t l y ag r e ed i n w ri t i ng by t h e P ar t i e s . 7 . 4 I f t h e P a rtie s agr e e i n w rit i ng to e x t e n d th e t i m e l i ne s s e t ou t i n W O , t h e P a rti e s w ill n e g o tiate i n g o od f a i t h t h e r e - ad j us t m en t of f e e s , i f a n y, in c o n s i de r a t i o n of t h e a g r eed re vi s e d dead li ne s and d o c u m e n t such ag r ee m en t i n a C O . 6 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N 7 . 5 I n t h e ev e n t t ha t any S tu d y i s p lac ed on ho l d fo r a p e r i o d o f t h i r t y ( 3 0 ) da y s or m or e f or r e a s o ns no t a t tr ib u ta b l e to I R OS or it s S u b c o n t ra c t o r s , CLIE N T w i ll c o m pen s a te I R OS f o r co s t s or e x pe n s e s i n c u r r e d f o r t h e pe r fo r m a n c e o f the S t u d y t h at c a n n ot r ea s o n a b l y be a v o i d e d or m i t ig a t e d i n c u r r e d during t h e hold p e r i o d i n a cc o r d a n c e w i t h t he W O . I f the d ela y i s lo n g e r t h a n t h i r t y ( 3 0 ) d a y s a n d t h e C L I E N T w i s h e s f o r any I R OS P er s o n n e l t o c o nt i n u e t o b e a l l o c at ed t o t h e S t u d y a nd p r o v i d e d th at I R OS h a s t h e s o l e d i s c r e t i o n t o ag r e e t o s u c h r eq u e s t (w h i c h w i l l no t b e u nr e a s ona b l y w i t hhe l d ) , t h e P a r t i e s s h a l l ne g o tiate a co mm e r c i a l l y r e a s o n a ble f e e to c ompe n s ate I R O S f o r th a t c o n t i n ue d allo ca t i o n , s h o u l d I R O S a g r e e to s u c h r e q ue s t . Such co mp e n s a t i o n s hal l b e s e t f ort h i n a C O . 8 . F O R C E M A J E U R E . 8 . 1 I n t h e e v e n t th at e i t h e r P a r ty sh a l l b e d e la y e d o r h i nde re d i n or p r e v en t e d f r o m th e p e r f o r m anc e o f a n y ac t r eq u ire d he r eun d e r a s a r e s u lt o f a Forc e M a je u r e E v e n t o cc u rr in g , t h e n p erf o r m a n c e o f s uch a ct s ha ll b e e xcu s e d for t h e pe ri od of s u c h de la y, p r o v i ded t ha t : 8.1 . 1 th e P a rt y cl a i m i n g F o r c e M a j e u r e n o t i f i e s th e o t he r P a rt y i n w r it i n g pro m p tl y on b e co mi n g a w a r e t h a t s u c h Fo rc e M a j e u r e E v en t h a s o c c u r r e d; 8 .1 . 2 t he P a r ty c l a i ming F o r c e M a j e u r e us e s re a so n a b le e f fo r t s t o m i tig a t e the e f f ec t s o f t h e F o r c e M aj e ur e Eve n t u pon t h e p erf or m anc e of i t s o b l ig a t i ons un d e r th i s Ag r ee m e n t a n d / or W O ; 8.1 . 3 w i th i n f i v e ( 5 ) ca l e n da r d a y s a f t e r t h e ce s s ati on of t h e Fo r c e M a j eu r e E ve n t , t h e P ar t y c l a imi ng F o r c e M a j e u r e n o t i f i e s th e o t he r P a r t y i n w r iti ng o f t h e ce s s a t ion o f th e F o r c e M aj e ur e E ven t a nd r e s u m e s p er f o r m a nc e of a ll i t s o b l i g a t io n s u n d e r t h i s Ag r ee m e n t ; and 8.1 . 4 th e P a rt i e s a g r e e a nd ackno w l e d g e t ha t fi nanc ial di ff i c u l t y s h all ne v e r b e dee m e d a F o rc e M aj e ur e Eve n t . 8 . 2 A n o n - af f ec t e d P ar t y s ha ll a l l ow t h e a f f ec t e d P ar t y a p e r i o d n o t exce e d i n g s i x t y ( 60 ) ca le n da r d a ys f r o m t h e da te o n w h i ch n o t i f i cati on of Fo r c e M a j eur e Eve n t i s r e c e ived b y t h e no n - a f fe c t e d P a rt y d u ri ng w h i c h t h e aff e c t ed P a r t y sha ll u s e re a s o nab le e n de a v o ur s t o m i t i g ate t h e e ffe c t of t h e F or c e M a j e u r e Ev e n t and t o ca rr y o u t i t s o b l i g ati o n s unde r t h i s A gr e e m e n t . I f su c h d e la y o r f a i l ur e p e r s i s t s for m o r e t han s i x t y ( 6 0 ) c a l e n da r days t hen t h e no n - a f fec t e d P a r t y m a y , i n i t s s o l e d i s c r e t i o n, t e r m i n ate t h i s A gr e e m e n t w i t h im m e d i a te e ffec t by w rit t e n n o t i c e t o t h e af f e ct e d P ar t y w it h o u t f urt he r lia b i l i t y t o e i t he r P a r t y, i n ac c o r da n c e w it h C l aus e 2 6 . 4 . 3 . 8 . 3 T h e corr e s pond i ng o b l i g a t ions o f t h e o t he r P a rt y w i l l b e s u spe n de d, a n d i t' s ti m e f o r pe rf o r m a n c e o f s uch o b l i g a t ions e x t ende d, t o t h e s a me e x t e n t a s t h os e of t h e P a rt y af f ec te d by t h e F or c e M a jeu r e E ve n t . 9 . V I S I T S A N D A UD I T S 9 . 1 T h e P arti e s a g r e e t ha t C L I E N T , i t s r e g ul a t o r s and th e i r ap p oin t ed re p r e s en t a t i v e s m ay v i s i t t h e S i t e s wh e r e t h e S t u d y i s be i ng c o n du c t e d . D u r ing t h e t e r m o f t h i s A g r ee m en t o n g i v i n g no t l e s s t han f o u r t een ( 1 4 ) da y s p r ior n o t i c e i n w rit i ng ( un l e ss s h o r t e r no t i c e i s requ ire d by a re g u l a t o r ) , C L I ENT , i t s r eg u l a to r s an d / o r th e i r s u i t ab l y q u ali f i e d r e p r e s en tati v e s m a y d u rin g r eg u l a r b u s in e ss h o u r s and at m u t ua l l y ag r eeab le t i m e s ( ea c h p a r ty a c t i n g r ea s o n a b l y ) , v i s it any s u c h S i t e w h e r e S e rv ic e s a r e be i ng p er for m e d or S t ud i e s a r e b e ing c o n d u c t ed i n o r d e r t o b e a s s u r ed t ha t s uch S e rv i c e s a n d / o r S t u d i e s co m p ly w i t h Ap p lic a b l e L a w s, i nc l u d i n g , a s a p p l i cab l e , Go od Cl i n i ca l P r ac t i ce s, t h i s Agr e e m e n t , a n d any C L I E N T s p e c i f ica t i o n s . A n y s uch i nspec t i on s ha ll b e f or t h e C L I E NT ' s ac c o u n t s av e t ha t I R OS s h a l l n o t b e e n ti t l e d t o re i mb u r s e m e n t of i t s o w n c o s t s incu r r e d i n p a r t i c i p ati ng i n a S i te v i s it i f s uch S i t e v i s it occu r s w it h i n t h e E mi ra te of Ab u D h a b i . I R O S s ha l l us e r ea s o n ab le e ff or t s t o pro c ur e ac c e ss t o a ny S i t e w h i c h m ay b e s u b ject t o an a u d it f or t h e p u r pos e s o f ena b l in g s u c h au d i t, a n d ag r ee s t o coop e ra te w i t h t h e a u d i to r s d u r i ng t h e p r oce s s . No t w i t h s t a n d i ng t h e f or go i n g , C L I E N T a ck n o w l e d ge s t h at a cce s s t o a n y S ite i s s u b j ec t t o t h e a p p r ova l a nd ac c e ss co n d i ti o ns of t h e t h ir d - pa r ty S i t e . 9 . 2 D ur i n g t h e ter m of t h i s A gre e m ent , CLIE N T or i t s s u i t ab l y q u a l if i e d re p r e s e n t a t i v e s h a l l h a v e th e r i g h t , no m o r e t h a n t w ic e a y e a r (u n le ss r eq u i r e d by a r eg u lato r ) , d u ri ng o rd i n ar y b us i ne ss hou r s a n d u pon f o u rt e e n ( 1 4 ) ca l e n da r days p r ior wr it t en n o t i c e ( u n l e s s s h o r t e r n o t i c e i s re q u i r e d b y a regu l a t o r ) , ga i n ac c e ss t o a n d au d it I R O S b o o k s , r e c o r ds and p r oced u r e s t ha t ar e re l e v a n t to 7 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N ( i ) v e r i fy c o m p l ia n c e w i th t h is A g r e e m e n t a nd a n y Ap p l i ca b le L a w s , ( iii) id e n t i f y o r i n v e s t i g a t e s u s pec t ed fr a u d , a n d / or ( i v) r e vi e w I R OS CLIE N T or i t s au d i to r s s h all p r o v id e a s pe c i f ic l i s t of d o c u m e n t s t h a t w i l l b e re q u e s t ed f o r t h e a u di t t o a l l ow I R O S to com p i le t h e r ec o r ds a n d c on te s t an y r eq uir e m e nt t h a t would b e i rr el e v a n t in the c o n te xt of s u c h a u di t . Th e c o s t s o f t h e a ud it i s th e re s pon s i b i li t y o f CL I EN T s a v e t ha t I R OS s h a l l no t b e e n t i t l ed t o r e i m b u r s e m en t of i t s o w n c o s t s i n c ur r ed i n pa rtici pa ti ng i n a n au d i t i f s u c h a u d i t o c c u r s r e m o t e l y o r w it h i n t h e E mi ra te o f Ab u Dh ab i u n l e ss th e r esu lt s o f s uch au d i t d i s c l o s e a m a t e r i a l v i o l at i o n of t h i s Agr e e m e n t or of a n y Ap p l i c a b l e La ws i n wh ic h c a s e I R OS s ha ll r ei m b u r s e C L I E N T f or i t s o w n re a so n a b le c o s t s a n d ex p e n s e s i n c urr e d . A ll i n fo r m ati on ob t a i n e d a s a r e s u lt of s u ch a u d it s h a l l b e C o n f i d e n t i a l In f o r m a t i o n t o t h e ex t en t s u c h i n f o r m a t ion m ay b e h e l d con f id e n t i a l l y u n de r A p p l i cab le L a w s . An y s u i t ab l y q u a l i f i ed r e p r e s e n ta tive a p p o i nt e d by for p ur p o s e s o f t h i s c l au s e 9 . 2 s h a ll b e s u bj e c t to c o n f i d e n t i a l ity o blig a t io n s no l e s s r e s tr i c t iv e t h a n t h os e s et f o rt h i n Cl au s e 1 7 w it h r esp e c t t o s u c h C o n f i d e n t i a l I n f o r m at i o n . 9 . 3 I R OS r e s e r v e s t h e r i g h t to l i m it d i s c l o s ur e of i t s p ro p r i et a r y i n f o r m a t i o n t o any th ir d - p a r t y C R O or p ha r m a ce ut i ca l d e v e l o p m e n t s e r v i ce s p r o v i d e r . 1 0 . S T A NDA R D S O F S E R VI C E S A N D R EG U L A T O R Y C O M P LI A N C E . 1 0 . 1 I R OS u n de rt ake s t ha t i t s S er v i c e s w i l l b e c o n d uc t e d i n c o m p l i anc e w it h t h e dead li ne s s e t ou t in t h e r e le v an t W O , G ood Cli n ic a l P r a ctic e s , t h e P r o t o c o l a nd Ap pli c a b l e L a w s r e le v an t t o t h e s c o p e o f wo r k en v i s a g e d unde r t h e app l i c a b l e W O . I n p a r t i cu l a r, I R O S s ha ll c omp l y w i t h, a n d s h all p r o c ur e t ha t I R OS P e r s o n n el co mp l y w it h, th e f oll o w i n g l eg i s l a t i o n , r eg u latio ns and g uid e l i n e s ( a s m a y b e a m en d e d f r o m t i me t o t im e ) i n t h e c o nduc t o f t h e S t u d ie s : 1. D O H S T A ND A R D O N H U M A N S U B J E CT R E S E A R C H ( D O H / QD / S D / H S R / 0 . 9 ) ; 2. D O H C o n s e n t G u i de l i n e ; a n d 10.1 . 3 Gu ide l ine s f or c o n d uc t i ng Cl in i c a l T ri a l w i t h inv e s t i g ati o n a l p r o d u ct s a n d m ed i c al dev i c e s ( M O H A P ) . 10.1 . 4 D O H Gu i d eli ne s for Co n d u c t i ng C l i n i c al T r i a l s w i t h I n ve s ti ga t i o n a l P rod u ct s and M e d ic a l D e v i ce s . 10.1 . 5 In t e r n ati o n a l C o u n c i l f o r H a r m on i s a t i o n of T echn ic a l R e q uir e m en t s f o r P ha r m ac eut i c a l s f o r Hum an U se G u i d e l i ne s f o r G ood Cl i n i c a l P r actic e E6 ( R 3 ) . and w i t h th e a dd iti ona l r e q u ire m en t s spec ifie d i n S c h e d u le 3 ( F D A R e q u i r e m e n t s ). 1 0 . 2 CLIE N T r ep r e s e n t s t h at it w i ll c o ope r a te i n go o d f a i t h w i t h I R OS i n ta k ing a ny ac t io n s t h a t I R OS r easo n a b l y b e l i e v e s a r e n e c e ss a r y f o r I R O S t o co mp l y w i t h t h e r e g u l a t o r y o b li ga t ions t h at h a v e b een t r a ns f e r re d t o I R OS and s h all u s e it s co m m e r c iall y rea s o n able e ff o rt s in t a k i n g s u c h a ctio ns . L i ke w i s e , I R OS r epr e s e n t s t ha t i t w i ll c o o p e r ate in good fa i t h w i t h CL I EN T i n t aking any ac t i o n s t ha t C L I E N T r easo n a b l y be l i e v e s ar e n e c e s s ary f or CLIE N T t o c o m p l y w it h re g u lat or y o b l i g a t i o n s re l a ted t o th e S e r v i c e s and s h all u s e i t s c o mm e rc i a l l y re a s o n a b l e eff o r t s i n t a k i ng s u c h a c t i o n s . 1 0 . 3 I R OS s h all i n f orm C L I E N T of a l l nec e s s a ry a m e n d m en t s t o t h e P r o t oc o l o r a n y de v i a t i o ns f r o m t h e P r o t oco l wh ic h a r e i m p e r at i v e t o a v o i d i m m ed i a t e d a n g e r t o t h e s u b j e ct s pro m p t l y on beco m i n g a w a r e o f t he se a m e n d m e n t s o r d e v i at i on s , a n d i m m ed i a t e l y t a k e a n y nece ss ary p r ec a u t i ons f o r th e p r o t e c t ion of a l l te s t su b je c t s . 1 0 . 4 I R OS ackn ow l ed g e s t h at any r ev i s i on t o t h e P r o t oc o l m u s t b e a p prov e d i n wr it ing b y CLIE N T and ap p ro v ed b y t h e r e le v an t Regu l a tory A u t ho ri t i e s b e fo r e a n y c han g e c a n b e m a d e t o t h e P r o t o c o l . 1 1 . R E P R E S E N T A T I O N S A N D W A R R A N TI E S 1 1 . 1 E ac h of C L I E N T a n d I R OS h e r e b y r e p r e s en t s, w arr an t s, and co v e nan t s t o t h e o t h e r at t h e E f f e ct i v e D a te and a s a t t h e e x ec u t i o n o f e a ch W O : 8 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N 1 1. 1 . 1 i t h a s the f ull r i g ht a nd a u t hor ity to e nt e r i n t o th i s Ag re e m e nt, a n d th a t n o c o n s e n t or au t h or i z at i o n no t ob t a i n e d p r i o r to th e E ff e c ti v e D a te a n d / or t h e d ate t h e r e l e v a n t W O i s execu t ed ( a s app lic a b l e) , i s n e c e s s a r y t o b e o b tai n e d ; an d i t i s n o t a w ar e o f a ny i m pe d i m en t w h ic h w o u ld su b s t a n t i a l l y imp a ir i t s a bil i t y to p e r f or m the t e r ms a n d c o n d i t i o ns imp o s e d on it by t h i s Ag r ee m e n t ; a nd 11.1 . 2 i t i s a c orp o r a t i o n val i d l y o r g a n iz ed u n d e r th e l a w s o f i t s i n c orpo r at i on a n d i s a u t ho r i ze d t o do bu s i n e s s t o t h e e x te n t n e c e s s a r y t o f u l f i ll it s o b l ig a t i o ns h e r e u nd e r . 1 1 . 2 CL I E N T r e p r e s e n t s a n d w a r r a n ts th a t it h a s o b t a i n e d or w i ll o b t a i n an y r eq u i re d c o n s e n t or a ut h or i z a t ion r eq u i re d by t h e approp ri a t e Re g u l a t ory A u t h o ri t y w it h r esp e c t t o t h e S tud y . 1 1 . 3 T he w a r r a n t ie s i n th i s Cl au se 1 1 s h all b e d e e m e d g i ve n a g a i n on t h e d a te the P ar tie s e x e c u te a W O . 1 2 . I N S PE C T I O N S. 1 2 . 1 D u r i ng t h e t er m o f this A g r ee m e n t, I R O S s h a l l n o t i fy C L I E N T p r omp t ly o n b ec o ming a ware of a ny ac t u a l or n o t ifi ed i ns p e c tio n of I R O S's p r e m i s e s or S i t e ( s) or i nq u i r y o r ac t i on by a ny Go ver n m e nt al E n t i t y wh e r e t ha t i ns p e c ti on, i n q u i r y or a cti on d i r e ct l y r e lat e s t o a S t u dy be i ng p e r f orm ed b y I R OS u n de r t h i s Ag r ee m e n t . I R OS s h all pr o m p t l y f u r n i s h c o p ie s o f a ll c o rr e sp o n d e n c e s, lette r s, n o t i fi c atio n s rel a t i n g t o s u c h ac t i o ns, i n sp e c t i o ns or i n q u i r ie s t ha t in v o l v e s uch S t u d y , and I R OS s h all p e r mit CL I E N T t o rev i e w and c o m m en t on r e s p o n s e s g i ven t o t h e G o v e rn m en t a l En ti t y p r i o r t o m a k i ng r espo n s e s . 1 2 . 2 I n t h e e ven t of a n i ns p e c t i on re q ue s t ed by a G ove r n m e n t a l E n t i ty a s pe r C l aus e 1 2 . 1 , I R OS s h a l l a r r a n g e ac c e ss t o t h e S i t e a n d t h e t h i r d p a rt y a n d s h all p e r mit s uch off i c er s t o c o py a n d v e r i f y a n y da ta r eco r ds and r e p o r t s i n I R O S . It i s un d e r s tood by t h e P a r t i e s t ha t i n t h e c a se o f a n y i n spec t ion o n S i t e , a n I R OS q u a l i t y a g e n t s ha ll b e pr e s en t . CLIE N T s h a l l hav e t h e r i g h t t o b e pr e s en t f o r and o b s e r v e a n y i n s p e c ti on r e l at e d to a ny S i t e ( o r o t h e r re l at e d v e n do r s) b y any Go v er n m en t al En t it y p ur po s e . 1 2 . 3 O n beco mi ng a w ar e o f any ac t i on ta k en by a n y G o v e rnm e n t E n t i t y t h at m a y a dv e r s el y im p a c t t h e S e r v i c e s i n a m a t e r i al m an n er , I R OS a g r ee s t o n ot if y C L I E N T a s s oo n a s r e a s o n a bly pr a c tic a b l e o f such a d ve r se im pac t ir r e spec t i v e o f w he t he r t h e a c t ion r e l a t e s di r ec t l y to a S t u dy be i ng p e r f o r m e d by I R OS u nd e r th i s Ag r ee m e n t . 1 3 . R E C O R D S A N D M A T E R I A L S . 1 3 . 1 I R OS s h a l l m ai n t a i n r e lev a n t R ec o r ds f o r a p e r i o d r e q u ire d by A pp l i cab le La w s a n d i n a c c o r d a n c e w i t h i t s o b l i ga t i o ns of c on f i d e n t i a l i t y a nd n o n - u s e i n t h i s Ag r e e m en t . S u c h r e c o r ds s ha ll b e m a i n t a i n e d i n a p r o p e r a n d orde r ed m a n n e r . C L I E N T s h all b e e n t it l ed to o b t ain co p i e s of any of th e Re c o r ds on r easo n a b le no t i c e i n wr it i n g , i nclu d i n g af t e r t e r mi n a ti on of t h i s Ag r ee m en t . 1 3 . 2 W it h o u t p r e j u d i c e t o C l a u se 26.1 1 . 2 , at t h e c o m p l e t i on of th e S e r v i ce s by I R O S , all m a t e r i a l s , i n f o r m at i on and a l l o t h e r d ata o w ned by C L I E NT , r e g a r dl e ss of t h e m et hod o f s t or ag e or r e t r i e v a l , s ha ll b e de l i v e red t o C L I E N T i n s u c h f or m a s i s t hen c u r r e n t l y i n t h e p o s s e ss i o n o f I R O S . A l t e rn a t i ve l y, a t CL I EN T w r i t t e n r e q ue s t , s u c h m at e ria l s a nd d a t a m ay b e r e tai n e d b y I R O S f o r CL I EN T f o r an ag r ee d - upon ti m e pe ri o d, or d i s p o s ed o f p ur s uan t to th e w r i t t en d i r e ct i ons of CL I EN T . C L I EN T s h a ll pay t h e r ea s o n a b le co s t s a ss oci a t ed w it h any o f t h e a b o v e o p t i o n s . 1 4 . C LI N I C A L T R I A L A GRE E M E N T S 1 4 . 1 T h e P a r tie s a gr e e t h at C l i n i c a l Tr i a l A g r ee m en t te mp lat e s sha ll b e u s e d b y t h e P ar t i e s wh e n co n t r a c t ing w it h I n s t it u t i o ns i n t h e Te rr i t o r y , u nl e ss e x pr e s s l y a g r e e d othe r w i s e and s p e ci f i ed i n a WO . 1 4 . 2 A s s e t f or t h i n a W O , I R O S ( a t it s c o s t ) m ay neg o t i a te t h e Cl i n i c a l Tr i a l Agr e e m e n t te r m s an d /or othe r S t u d y - t o p r o v i d e t im e l y f e edback i n c o n n e c t ion w i t h a n y s u c h n e g o t i a t i o n s, a n d I R OS sha ll n o t b e r e s p o n s i b l e 9 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N f o r a ny und u e d el a ys a t t r ibut a b le to C LI E N T ' s fa i lure to p r ov i de a p p r o v a l s a nd tim e ly r e s p o n s e s . I R O S m u s t s ecu r e C L I E N T a p pro v a l of a l l C l in i c a l T rial A g r e e m e n t s p ri or to e x e c u t i o n. 1 5 . P A Y M E N T OF FE E S AN D E X P E N S E S . 1 5 . 1 I n c on s i d e r a t ion for t he p er f o r m an c e o f t h e Se r vi c e s b y I R O S i n a cc ord a n c e w ith t h is A g r e e m en t a nd t h e r e le v an t W O , C L I EN T w i l l p ay I R OS f o r f ee s, e x pe n s e s a nd p a ss - t h r o ugh e x p e nse s in a cco r dan c e w i t h t h e b udge t a n d p a y m e n t s c h e du le c o nt a i n e d i n each W O or a s s oc i a t ed C O . U n l e s s o t h e r w i s e a g r eed i n a p a r t i c u l a r W O , the f o l lowing s h a ll a p p l y : ( i ) I R O S w i l l invoi c e C L I E N T monthly fo r t h e f ee s , e xp e n s e s and pa s s - th r o u g h exp e n s e s ( s u bj ect t o c l a u s e 1 5 . 2 ) inc u r r ed i n p e r fo r m i n g t h e S e r v i ce s ; a n d, ( i i ) CLIE N T s h a l l p a y e ach in v o i c e w i th i n t hi rt y ( 30 ) d a y s o f t h e d a t e o f r ece i p t o f s u c h i n v oic e . 1 5 . 2 F o r t h e a v o i da n c e o f dou b t th e CLIE N T w i ll b e s o l e l y r e s p on s i b l e f o r m ak i ng d ir ec t p a ym e n t of a n y f ee s , ex p e n s e s o r o t h e r c o s t s t ha t ar e paya b l e t o a n I n s t it u t i o n u nde r a C l i n i c al T r i a l A gr e e m en t t o e ach s u c h I n s t i t ut i o n , s av e wh e r e ex p r e s s l y agr e ed o t he r w i se u n d e r a W O . I R O S s h a l l hav e n o lia b i li t y for a n y f a i l u r e by C L I E N T t o m ak e p a ym e n t s t o I n s t it u t i o ns u n d e r e ach C l in i c a l T rial A g r e e m e n t . Each Cl in i c a l T r ial A g r ee m e n t s h all c ont a i n a stat e m e nt t o th a t e ffe c t . 1 5 . 3 A ll su m s p a y a b le t o I R OS u nd e r th i s A g r e e m e n t : 15.3 . 1 ar e e xc l us i v e of V A T , eq u i v a l e n t s a l e s t ax or a ny ot h e r ta xe s, cha r g e s , l e v i e s a ss e s s m en t s and o t he r f ee s of a n y k i n d i m p osed on th e S e rv i ce s and C L I E N T s h a l l i n a d d it i o n p a y an a m o u n t e q ua l t o a ny V A T ch ar g e a b le on t h os e su m s o n de l i v e r y of a V A T i n v o i ce ; and 15.3 . 2 s h all b e p a id i n f u ll w i t h o u t a n y s et - off , coun t e r c l a im , d e du cti on o r w i t h h o l d i n g (o t h e r th an any d e d u c t ion o r w i t h h o l d i ng o f t ax a s r e q u i r e d by A pp l i ca b le La w s ). 1 5 . 4 W it h o u t p r e j u d i c e t o any o t he r ri g h t or re m e dy t ha t i t m a y h a ve , i f C L I E N T f a i l s t o p a y : 15.4 . 1 I R OS a n y s u m d u e unde r a n y W O on t h e d u e d at e : ( i ) a nd CLIE N T h a s s t i l l n o t m a d e pa ym e n t w it h i n th irt y ( 30 ) d a ys of a w ri t t en re m i n d e r f r o m I R O S t o m ak e pay m e n t , I R OS m ay s u s pend t h e S e r vic e s u n d e r th e r e l e v a n t W O u n t i l p a y m e n t ha s be e n m ad e i n f u l l ; a n d ( i i ) CL I EN T s ha l l p ay i n t e r e s t o n t h e o v er d u e su m fr o m th e du e da t e u n t il p a y m e n t of t h e o v e rd u e s u m , wh et h e r b e f or e or af t e r j udg m en t . I n t e r e s t unde r t h i s cl a u se w ill ac cr u e ea c h d ay at 2 % a y e a r a b o v e t h e C e n t r a l B ank of t h e U A E ' s b a s e r a te fr o m time t o t im e, b u t at 2 % a y ea r f or any pe r i od w h e n t h at b a se r a te i s be l ow 0 % ; and /o r 15.4 . 2 an I n s t i t u ti on i n a c c o r d a n c e w it h t h e t e r m s of t h e a p pl i c a b l e Cl i n i ca l T ri a l A g r e e m e n t , I R OS m ay s u spe n d th e S e r v i c e s und e r t h e rel eva n t W O i n r e s p e c t of such I n s t i t ut i o n , u n t i l p a y m e n t ha s been m a d e i n f u l l . 1 5 . 5 I f CLIE N T i n good fa i t h w i she s t o d i s p u te an i nvo ic e i s s u e d un d e r th e t e r m s of t hi s A g re e m e n t a n d t h e ap p l i c a b le W O , CLIE N T s h all n ot i f y I R OS of any d i s p u t ed a m o u nt s w i t h i n t en ( 1 0 ) days of t h e da t e of D i s p ut e No t i c e CLIE N T d i s p u t e s o n l y a p o r t i on of a n in v o i c e/ p a ym e n t r eq u e s t, t hen t h e CLIE N T s h all p a y t h e u n d i s p u t ed a m o u n t s a s i n a cco r danc e w it h t h e te r m s of t h i s Ag r ee m e n t a n d t h e a pp lic a b l e W O and t h e P a r t i e s s h a l l u s e g ood f a i t h e f fo r t s t o r e c o nc i l e t h e d i s p u te d a m o u n t a s s o o n a s te a m s w i ll u se g ood f ait h e f fo r t s t o re s o l v e such d i s p u te w i t h i n t en (10) d a ys of t h e da te of C L I E N T ' s D i s p u te No t i ce . T h e P a rt i e s a g r e e t ha t t h e r e s u l t o f t h e se d i s cu s s i o ns w i l l b e b i nd i ng o n bo t h P a r t i e s. I f no a g ree m e n t c an b e r ea c h e d by th e p a r tie s i n r el a t i on t o CLIE NT ' s D i s p u te No t i ce , c l au s e 36.3 of t h i s Ag r ee m e n t w i ll a p p l y. 1 5 . 6 Up on t h e rea s o n a b le re q ue s t o f I R O S , C L I E N T agr e e s t o p r o m p t l y p r ov i d e w r it t en a s s u r anc e t ha t CL IE N T i s i n p os s e s s i o n of t h e fi n a n ci a l re sourc e s s u ff i c i e n t t o m ee t a ll an tici pa t ed fi na n c i a l o bl i ga t i o n s t o c om ple t e t h e S tu d y a n d t o de m o n s trate i t s fi n a nc ial a b i l i t y t o m ee t i t s f in a nci a l o b l iga t i ons u n d e r t h i s Ag r ee m e n t and e ach W O . A ny f i na n ci a l s t a t e m en t s o r o t h e r i n f orm a t io n p ro v i ded t o I R OS u n de r t h i s C l a u s e s h all b e k e p t co n fi d e n t i a l . 10 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N 1 6 . F O R EI G N C U R R E N C Y E X C H A N GE 1 6 . 1 T h e c u r r e n c y t o b e us e d f o r in v o ic e a nd p ay m e n t s ha ll b e th e c u r r e n c y s tat ed i n t h e W O . 1 7 . C O N F I D E N T I A L I T Y . 1 7 . 1 E ac h Par t y un d e r t a k e s to t he o th e r P a r ty t o t r ea t a s c onf i d e n ti a l a l l Conf id e ntial I n f o r m ati o n p r o vi d e d to t ha t P a rt y by a n y o t h e r P a r t y . A P art y sh a l l n o t di s c l o se any C o nf i d e n t i a l I n f or m a t i on it r e c ei v e s f rom t h e o t h e r P a r t y un d e r t h i s A g re e m e n t , u nl e ss oth e r w i s e agr e ed b y t h e o t he r P ar t y or a s p e r mit t ed unde r this Cl au se 1 7 . 1 7 . 2 W h e n CLIE N T i s ac t i n g in th e c o n t ex t o f a S tu d y o n b e ha l f o f a th ir d par t y en ti t y w ho s e p r oduc t i s t h e s u b ject of t h e S t u dy, C L I EN T s h all hav e th e r i g h t t o d i s c l os e any C o n f i d e n t i a l In f o r m a t i o n r e ce i v ed f r o m I R OS u n de r t h i s A gre e m en t a n d / or a W O , t o t h e e x t en t n e c e s s a ry f or t h e purp o s e s o f t h e co n d u ct of t h e S tu d y, an d pr ovid e d th a t su c h e nti t y is m a d e a w a r e o f s u c h c o n f i d e n t i a l i ty o b l ig a t i ons a n d is b o u nd by s i mi l a r c o nf i d e n t i a l i t y obl i g a t i o n s t ow a r d s CLIE N T . 1 7 . 3 T o t h e e x t en t t ha t a ny C o n f i d e n t i a l In f o r m a t i o n i s requ ir ed t o b e d i s c l o s ed b y Ap p lic a b l e L a ws , r eg u l at i o n or a n y g o ve r n m e n tal or co m p et e n t r e g ula t o r y a uth o ri t y ( i n cl u d i ng any s e c u r i t i e s e x c han g e ) , a P ar t y m a y d i s c l o s e s u c h Co nf i den tial I n fo r m a t i on p r o v i d e d t ha t, t o t h e e x te n t re a s ona b l y pr a c tic a b l e and l e g a l l y p e r m i s s i b l e , t h e P a r t y req u ire d t o m a k e such d i s c l os ur e s h a ll c o n s u lt i n a d vanc e w it h ( a n d ta k e i n to ac c o u n t th e r ea s o n a b le r e q ue s t s o f ) t h e o t he r P a rt y on t h e p r opo s e d f o r m , t i mi ng, con te n t and p u r p o s e of t h e d i s cl o su r e . 1 7 . 4 E ac h P a rt y u n de r t a k e s t o : 17.4 . 1 di s c l os e t h e o t he r P a r t y's Co n f i d e n t i a l In fo r m a t i o n o n l y to t h os e o f i t s o f f i c e r s , e m p l o ye e s, age n t s , co n s ul t a n t s , p r o f e s s i ona l a d v i sor s, A f f i liat e s and c o n tr ac t o r s t o w h o m and t o t h e ex t en t to wh i c h such d i s c l os ur e i s ne ce s s a ry f o r t h e pu r po s e s co n t e m p l a te d unde r thi s Ag r ee m e n t, and p ro v i d e d t h a t s uch pe r s o ns a r e u n de r a s i m ila r o b li ga t i on of conf i de n t i a l ity ; 17.4 . 2 p r ocu r e tha t s uch pe r s o n s a r e m ad e a w a r e o f t h e o b l i ga t i o ns u n de r t h i s C l a u se 1 7 ; a n d 17.4 . 3 b e r e s p on s i b l e f o r all ac t s a n d o mi s s i o n s of s u c h p er s o n s w ho a r e g i v e n a cce s s t o t h e C o n fi dent i a l In f o r m a t i on a s tho u g h t hey w er e i t s o w n ac t s or o m i ss io n s u n de r t h i s Ag r ee m e n t . 1 7 . 5 T h i s C l a u s e 1 7 s h all n o t a p ply t o a n y i n f o r m a t i o n wh ic h : 17.5 . 1 a t t h e t i me of it s d i s c l o s u r e b y ( o r on beha l f o f ) a P a r t y i s i n, or s u b s e q u e n t l y c om e s i n t o, th e p u b l i c do m a i n , e x c e p t th r o ugh b r e ach o f a ny o f t h e un d e r ta k i n gs s et o u t i n t h i s Agr ee m e n t; 17.5 . 2 i s a lr eady i n t h e l a w f u l p os s e s s ion of a P a r t y , a s e v i denced by wr i t t en d o c u m e nt a t ion m a i n tai ned pri or t o t h e d i s c l o s u r e of t h e Co n f i den t i a l I n f o r m ati on or w h i ch i s i n d e p e n d e n t l y d i s co v e r ed by a P ar t y, a f t e r t h e da te h e r eo f, w i thou t t h e ai d, a p p lic a t i on, or u s e of t h e C o n fi dent i a l I n f o r m a t i o n o f t h e o t h e r P a r t y , a s ev i denc e d b y w r i tte n r ec o r d s ; o r 17.5 . 3 s u bs e q u e n t l y c om e s l a wf u l ly i n t o t h e p o s s e s s i on of a P a r t y fro m a t h i rd p a r t y w h o d oe s no t o w e th e d i s c l o s i ng P a r t y an o bli ga t i on of con fi denc e i n r el a t i o n t o it a n d w h o d i d n o t o b ta i n 1 7 . 6 W it h o u t af f ec t i n g a n y oth e r r i g h t s or r e m e d i e s t h a t a P a r t y m ay ha v e, e ach P a r ty ackno w l ed g e s t ha t t h e o t he r P a r t y m ay b e i r r e p ar a bl y h ar m e d b y any b r e a c h of it s t e r m s a n d t ha t d a m a g e s al o n e m a y no t nece s s a r i l y b e an a d e q ua te re m e dy . A c c ord i ng l y, each P a r t y a c k n ow le dge s ( w i t h o u t p r o of o f a c t u al da m a g e s ) t ha t i n j u nc t i v e r e l i e f , s pec if i c per f o r m a n c e o r o t h e r eq u i t ab le r e l i e f i n fa v o r of th e o t he r P a rt y t he r eof m a y b e a n a p p r o pr i a t e a n d nec e ss a ry r e m edy fo r an y t h r ea te n e d or a c t u a l br e ach of t h e t er m s o f t h i s Cl a u se 1 7 . 11 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N 1 7 . 7 T h e c o n f i d e n tiali t y o b l i g ati ons u n d e r t hi s Cl a u se 1 7 s h all s u r viv e t h e ex p i r y or ea r l y t e r m i na t i o n of t hi s Ag r ee m e n t f or a p e r i od o f f i v e ( 5) y ea r s a fte r exp ir y o r t e r m i n ati on o f t h e la s t W O . 1 8 . P U B L I C A T IO N . 1 8 . 1 S tu d y r e sults m a y n ot be pu b l i s h e d or r e f er re d t o , in w h ole or i n p a r t, by I R O S w ith o ut the pr i o r e xp r e s s w r i t t e n c o nse n t o f CLIE N T . N e i t h e r P a rt y w ill u s e th e o t he r P p u b l i c a t i o n o r p r o m o tio n w i t h o u t t h e o t h e r P 1 8 . 2 N e i t he r Pa r t y s h a l l b e p e r m i tt e d to i ss u e a ny in f o r m a t i o n o r s t a t e m e n t to t h e pr e s s or p u b lic r e l a ting to t he i r c o l l ab o r a t i on i n t h e c o n te x t of t h e A g r ee m en t w it ho u t pr i or r e v ie w a n d wr i t t en a p p r ova l o f t h e oth e r P a r t y, wh i ch co n s en t s h all n o t b e un r e asona b l y w i thh e l d . 1 8 . 3 N e i t h e r P a rt y sh a l l b e p e r m i tte d t o u s e t h e n a m e s o r l o g o s o f t h e o t h e r P a r ty i n a ny p u b l i c i t y , a d v er t i s i ng or n e w s r el ea s e, i n r e la tion to a S t u dy o t he r s o ci a l m e d i a w i t h o u t t h e p ri o r c o n s e n t of t h e oth e r P ar t y , wh ic h co n s e n t s h all n o t b e u n r ea s o nab l y w it h h el d. 1 9 . O W N E R S H I P OF I N T E LL E C T U A L P R O P E R T Y A N D D A T A . 1 9 . 1 T h e Ba ck g r o und I P of e a c h P a r ty i s a nd s h all r e m a i n t h e p r o p e rt y of th at P a rt y or i t s Af f i l i a te s or t h i r d p a rt y l i ce n sor s, a s a p pl i c ab l e . Excep t a s s e t o u t i n t h i s A g r e e m e n t , nei t h e r P a r t y, n o r a n y o f i t s A f f i l i a te s , . 1 9 . 2 A ll m at e r ia l s, d o c um e n t s , i n f or m a t i o n a nd da t a , i n c l u d in g G e nera t e d D at a, s u pp li ed t o I R O S by C LIE N T or g e n e r a t ed on b e h al f of C L I E N T i n t h e p e rfor m a n c e o f t h e S e rv i c e s u n d e r t h i s A g r e e m e n t ( ) w ill b e t h e s o le a nd exc l us i v e p r oper t y o f t h e C L I E N T . CLIE N T : 19.2 . 1 i s r e q ui r ed t o ob t a i n a l l a p p li c a b l e l i c e n s e s r e l a t ed t o a n y s c a le , a s s e s s m en t, q u e s t i o nna i r e , m ea s ur e or simi l a r i ns tr u m e n t t ha t C L I EN T r e q u e s t s I R OS t o u s e f o r a n y S t ud y ; 19.2 . 2 g r a n t s t o I R OS a no n - exc l u s i ve , r o ya l t y - f r e e lic e n s e, w i t h a r i g h t t o su b l i cens e t o I R O S A ff i l i a t e s , I R OS P e r s o n n el and Sub c o n t rac t o r s , t o u se C LIE N T B a c k g r ou n d I P , C L I E N T P r o p e r t y a n d Re s e a r c h I P to t h e ext e n t need e d t o a ll ow IR O S t o p e r f o r m t h e S e r v ic e s a n d exe r c i se a n y o t h e r r ig h t s o r p erf o r m a ny o t h e r o b l i g ati ons u n d e r t h i s A gr e e m ent . 1 9 . 3 I R OS s h all p r o m p tl y di s c l os e t o C L I EN T a n y I n t e l l ec t u a l P r oper t y or ( i i ) C L I EN T P r ope r t y , in e a ch c a s e wh ic h w a s co n c e i v e d or g e n era t ed by I R O S , I R O S P e r s o n ne l or S u bco n tra c t o r s w h ile p ro v i d i n g t h e S e r v i c e s unde r t hi s A g r e e m e n t or b y I n s t i t ut i ons i n pa r t i c i p ati ng i n a S t u d y ( t h e ) . T h e re f o r e , i n co n s ide r a t i o n of t h e p a y m en t of t h e f ee s u n de r t h e r e l eva n t W O , I R O S he r eby exc l u s ive l y a s s i g n s to CLIE N T , wor l d w ide , and f or any pu r pos e w ha t soeve r, a ll Re s e a r c h I P w it h e f f e c t f rom it s c r ea t i o n , f or t h e e n t i r e d ura t i on o f such In t e l l e c t u a l P r o p e r t y Ri g h t s, a n d u n der t ak e s t o pe r f o r m , a t a l l ac t s d ee m e d n e ce s s a r y o r de s ir ab le b y C L I E N T or it s s ucce s s o r s to pe r mit a nd a s s i s t i t i n o b t a i n i ng a n d e nf o r c i n g t h e f ul l b e n efi t s, e n j o y m e n t , r i gh t s a n d t i t l e t h r oug h o u t t h e w or l d i n s u ch In telle c t ua l P r o pe r t y, i n c l u d i n r eq u e s t . Dur i ng a n y p e r io d i n w h i ch s u ch a s s i g n m e n t o f f u t ur e In t e l l e c t u a l P r ope r ty i s n o t ef fe c t i v e p ur s u a n t t o a p p l i c a b le l a w , t h e I R O S s h a ll l i c e n c e t h e u se of s uch I n t e l l e ctu al P r o p e r ty t o C LIE N T o n a wo r ld w i d e , exc l u s i ve , pe r pe t u al, s u b lic e n s a b le and r o y a l t y - f r e e b a s i s . 1 9 . 4 1 9 . 5 I R OS r e pr e s en t s and w a rr a n t s t ha t t h e R e s ea rch I P be i ng c r e a t ed by I R OS P e r s o nnel , S u b co n t r ac t or s a nd I n s t i t ut i ons u n de r t h i s A g r e e m ent , a r e or s h all b e a s s i g n e d to I R OS on w r i t t en t e r m s ve s ti ng o w ne r s h i p of t h e R e s ea r ch I P to I R OS ( and l i c ensed t o I R O S d ur in g a n y pe r i o d i n w h i c h s uch a s s i g n m e n t i s i ne f fe c t i v e ) , s o a s no t t o l i mit t h e In telle c t ua l P ro p e r t y a s s i g n e d an d /or l i c e n s ed t o CLIE N T p ur s u a n t t o 1 9 . 4 . 1 9 . 6 No t w i t h s t a n d i ng t h e f o r e g o i n g , t h e C L I E N T ac k n o w le d g e s t ha t I R O S B a c k g r o u n d I P , i n cl ud i ng ana l y tic a l m e t h o d s , p r o c e d ure s a n d t e c h n i q ue s , co m pu t e r te c h n i c a l e x p e r t i s e, ha r d w ar e and sof t w a r e , 12 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N m a y be u s e d i n t h e c ou r se of p r ovid i n g t h e S e r v i ce s . To t he e x t e n t s u c h I R O S Ba c k g ro u nd I P is u s e d , im p ro v e d o r m od i f ie d by IR OS u n de r o r du r ing t h e t e r m o f th i s Agr e e m e n t , s uch im pro v e m e n t s o r m o d i f i ca t i o ns s h all b e d ee m ed t o b e I R O S Back g r ound I P . F or t h e av o i d a n c e of d o u b t : 1 9. 6 . 1 s t i t l e in a n y d e l i v e ra bl e s s t emming fr om t he S e r vi c es, a nd a ny r ig h t s in I nt e l l e c t u a l P ro pe r t y e m bo d i e d i n t h e d e l iv e r a b l e s, sha ll n o t ex t end t o a n y I R OS B a c k g r o u n d I P i nc l u ded i n s u c h d eli ver a b l e s b y i mp l i c ati on or o t he r w i s e . W i t h r e s p ect t o s u ch I R O S B a c k g ro und I P , I R OS g r a n t s th e CLIE N T a n o n - e xc l us i ve , n o n - t r a nsf e r a b l e l i c e n se t o us e the I R O S Ba ck g r o u n d I P to t he ex t en t n ec e s s a ry t o m a k e u s e o f su c h de l iv e r ab l e s a nd to a l l o w us e of s u c h d eli v er ab l e s by t hi r d pa r t i e s p ro v i ded th at a ll u s a g e r e m a i n s in ac c o r da n c e w it h t h e t e r m s o f t hi s A g r e e m e n t ( a s a p p l i c a b l e ) a nd in c o m p l i anc e w it h all a p p lica b l e la w s ; a nd 19.6 . 2 n o t h i ng in t h i s C l aus e 1 9 s h all b e c o n s t ru e d so a s t o prev e n t I R O S fr o m u s i ng i t s kn ow - h o w g e n e r at ed d uri ng t h e per f o r m a nc e of t h e S e rv i ce s i n t h e f u r t h e r anc e o f i t s nor m a l ac t i v it i e s , P r o p e r t y or C o n fi d e n t i a l I n f o r m a t i o n. 2 0 . I N SU R A N C E . 2 0 . 1 I R OS m u s t s e c u r e a n d m a i n t a in i n fu ll f o r c e and e f f e c t t h ro ugh o u t t h e t e r m of ea c h W O ge n e r al a n d p r o f e s s i o n a l l i ab il i t y co v e ra g e of a m o u n t s i n a cc o r d a n c e w it h ge n e r all y a cc e p t ed s t a n d a r d s by C R O s, t o co v e r a l l l os s e s , d a m a g e , li a bil i t y o r co s t s w i t h r e s pec t t o wh i ch it i s lia b le u n d e r t h i s Ag r ee m e n t . I f CLIE N T s o r eque s t s i n wr it i n g, bu t n o m o r e f r e q u e nt l y t h a n onc e e v e r y t w e l v e ( 1 2 ) m o n t h s , I R OS w i l l p r odu c e a c e r t if i ca te o f i n s u r a n c e f or r ev i e w or s uch oth e r d ocu m e n t e v i d e nc i ng t h at i t ha s ade q ua t e co v e r a g e c on s i s t en t w it h h u m a n c l in i c a l trial i n d u s t ry s t an d a rds t o co v e r i t s o b l i g atio n s he re u n d e r , a n d i n no e v e n t l e s s t han th e mi n i m u m a mo u n t o f i n sur a n c e r e q ui re d by A p p l i cab le La w . 2 0 . 2 CLIE N T or t h e t h ir d pa r ty en ti ty o n be h al f of w h i ch t h e S t u dy i s c o n d uc t e d m u s t s e c u r e a n d m a i n t a i n i n f u l l for c e and e f fe c t t hro u g ho ut t h e te r m of ea c h S t ud y , and w i t h a r e p u ta b le in s ur e r , a n i n s u r a n c e p o l i c y t o c o v e r a n y i n jur y o r d a m a g e s s uff e r e d b y S tu d y s ub j ec t s r e s u l t i n g f r o m t h e p e rf o r m anc e o f t h e S tu d y w it h r e s pec t to wh i ch th e s p o n s o r i s l i ab le u n d e r t h i s Agr e e m e n t , of a mo u n t s i n a cc or d a nc e w i t h Ap p lic a b l e L a w s and g e n e r a ll y acc e p te d s t an d a r ds f o r sp o n s or s i n c o n n e c t ion w it h th e ad mi n i s t r ati on o f i nve s t i ga t i o na l c o m poun d s or cli ni c a l t r i a l s . Such i ns u r anc e sha ll n o t c o n t a i n e x c l u s i ons t ha t wo uld p r e c l u d e c l a i m s b y p a r t i c ip a t i n g S t u d y s u bj e c t s wh ic h a r i se f r o m th e S t u d y i n r el a t ion t o t h e i nve s t i ga t i o na l p ro d uc t, w h e r e t h e S t u d y p a r t i c i p a n t h a s r ea s o na b l y c o m p l i ed w i th t h e P r o t o co l . 2 0 . 3 W it h o u t l i mit i n g t h e g e n e r ali ty o f t h e f oreg o i n g C L I EN T s ha l l m a i n t a in f or t h e t e r m o f t h i s A gr e e m en t and for a p e r i o d of 3 (t hre e ) y e a r s f r om t h e e x p ir a t io n or t e r m i na t i o n o f t h e l a s t WO , c l i n i c al t r i a l l i ab il i t y or p ro d uct s l i a b i l i t y i ns u r anc e w i t h co v e r a g e e q ua l t o t h e g re a t e r of : ( i ) n o t l e s s th a n $ 1 0 , 00 0 , 0 0 0 U S D p e r occurr e nce /a g g r e g at e , ( i i ) t h e s ta t u t o ri ly m a n da t ed c o ve r ag e a n d ( ii i ) t h e m i n i m u m a mo u n t o f i ns u r anc e cove r ag e d i c t a t e d by a n y e t h ic s c omm i t t e e or in depen d en t r e v i e w b o a r d . 2 0 . 4 I R OS and it s A f fi l i a t e s s ha ll b e i d e n t i f i ed a s add i t i o n al i n s ur e d s o n C L I E N T CLIE N T and i t s A f fi l i a t e s sha ll b e i den ti f ie d a s ad d i t iona l i n s u re d s on p o l i c y. 2 0 . 5 Up on w r itte n req u e s t , ea c h P a r t y s ha l l p r o v i d e t h e o t he r w i t h a c o py of it s e ffe c t iv e c er t i fi ca t e o f i ns u ra n c e or s uch o t he r d o c u m e n t e v i d e n c i ng t ha t it ha s a d e qua te c ove r a g e c on s i s t en t w i th h u m a n c li n ic a l t ri a l i nd u s tr y s t a n d a r d s to co v e r it s o bl i ga t i ons he r eun d er, a n d i n n o e v en t l e ss t han t h e m i n i m u m a m ou n t of i ns u r anc e r e q u ire d by A pp lica bl e La w s . C L I E N T he r eby a ut h o riz e s I R OS t o pr o v i d e i t s S u b c o n tra c t or s w it h a c o py o f ce r t ifi c ate of i n s u r anc e . D A T A P R O TE C T I O N A N D S E C U R I T Y 2 1 . 2 1 . 1 Bo t h P a rt i e s h a v e th e o b l i ga t i o n t o a b i d e by t h e pr in c i p le of m e d i ca l c o n f i d e n t i a l i t y f o r t h e s ub j e ct s p a rt i c i p a t ing in a S t ud y . 2 1 . 2 F o r t h e pu r p o s e of t h i s A g re e m en t, e ac h P a r t y s h a ll p r o v i d e t o t h e o t h e r P ar t y o n ly A non y m i zed D a t a r e lat ed t o t h e S t u d y s u b j e c t s . 13 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N 2 1 . 3 E ac h P ar t y ack n o w l edge s a n d ag r e e s t ha t , a n d s h all p r ocur e t h a t i t s d i r e cto r s , e m p l o yee s a n d a u t ho r i z ed s u bco n t r a c t o r s : 21.3 . 1 s h all c om p l y w i t h t h e t e r m s o f U A E F ede r a l L a w N o 2 o f 2019 o n t h e Us e o f th e I n fo r m atio n a nd C ommu n i c at i o ns Tec hn o lo gy in Health F i e lds (a s a m e n d e d or u p d a t e d f r o m t i me to t i m e ) a nd a ny oth er a ppl i ca ble P r iv ac y L a w s ; 21.3 . 2 s h all a t a ll t im e s en s u r e t h e p r o t e cti on of t h e pr i v a cy o f hu m an s u b j e ct s , c o m p l y w i th a ll h ea l t h inf or m a t ion a nd Ano n y m i z e d D a t a ; a nd 21.3 . 3 s h all o n l y u se S t u d y and t h e An ony m i ze d D a ta f o r t h e p u r p o se of t h e r el a t ed S t u dy a n d n o t f o r a ny o t he r p u r p o s e or i n a n y w a y c o n tr a r y t o l e ga l r e q u ire m e n t s. 2 1 . 4 S u bj e c t t o c l a u s e 2 1.1 and t o th e e x t e n t th at I R O S p r o c e s s e s P e r s o n al D a ta r e la t ed t o th e S t u dy S u b j e ct, in r e sp e c t o f t h i s P er son a l D a t a a nd t he Ge n e r at e d D a t a , I R O S s h a l l : 21.4 . 1 o n l y u s e t h e P e rso n al D a ta and t h e G e n e r at e d D a ta f or th e p u r p o s e of th e r e l a t ed S t u d y i n ac c o r da n c e w i th t h e p r o v i s i ons o f t h i s A g r e e m e n t , and n o t f o r any o t h e r p u r po s e or in a ny w ay c o nt r a r y t o le g a l r equ ire m en t s, a l w a ys i n co m p l i a nc e w i t h all a p p l i cab le P ri v a cy L a w s ; 21.4 . 2 t a k e ap p ro p ri a t e s t eps t o pro te c t t h e c o n f i d e n t i a l i t y a nd s e c u r i t y of t h e P e r s o n al D a ta and t h e G e n e r at ed D a ta wh i l e i n i t s p o s s e ss i o n or co n t r ol ; 21.4 . 3 s u b je c t t o c l a u s e 21.4.4 be l o w , n o t t o d i s c l o s e P e r s ona l D a ta and G en e ra t e d D a ta to any t h i r d p a rt y exc e p t : ( a ) t o any a utho riz ed ind i v i dua l s i n vo l v e d in t h e S t udy to w ho m d i s c losur e i s s tr i c t l y n ece s s a ry i n ord e r fo r t h e p erf o r m a n c e of it s o b li ga t i o ns u n de r th i s Agr e e m e n t p r o v i d e d t ha t s u c h in d i v id u a l s ar e obl i ged t o pr o c e ss t h e P e r s o n al D a t a a n d G e n e r at ed D a ta i n ac c o r d a n c e w i t h t h e p r ov i s i o n s of t hi s Ag r ee m en t ; o r ( b ) i f r e q u ir ed t o do s o b y a n y l e g a l r e q u i r e m e n t s, i n c l uding w i t h r e spec t t o prov i d i ng t h e P e r so n al D a t a t o any c o m pe te n t G o v er n m e n t a l En ti t y p r o v i d e d t h at I R OS o n l y p r o v i d e s t h e m in im u m P e r s o n a l D a t a nece s s a r y t o s a t i s fy t h e r eq u ire m e n t . 21.4 . 4 n o t tra n s f e r any P e r s on al D a t a o u t s i d e o f t h e U A E u n l e s s p e r mit t ed b y , a nd in a cco r dan c e w it h t h e r equ i re m e n t s o f, a ppl i c ab le P r i v acy L a w s , o r i f in s t ru c t e d by a ny c o m pe t en t au t h or i t y ; 21.4 . 5 i m p le m e n t a nd m ai n t a i n a p p r o p r i a t e p h y s i c al, a d m i n i s tr a t i v e, and te chn i c a l s a f egua r d s t o p r o t e c t t h e P er s o na l D a ta a nd t h e G ene r a te d D a t a f ro m i n ad v e r t en t or u n a u t h or i z e d a cc e s s, d i s c l o s ur e , u s e, o r m o d i f i ca t i on D a t a B r e a c h , t a k i n g i n t o a c c o u n t th e s en s i ti v i t y o f s u c h d a t a ; 21.4 . 6 p r o m p t ly a n d i n any ev e n t w i t h i n t w e n t y - f o ur ( 24 ) ho ur s i n f orm t h e CL I EN T u p o n be c o m i n g a w a r e of a D ata B r each or a r e q u e s t f r o m an i n d i v i d u al t o e x e r ci se a r i g h t u n de r a p p l i c a b l e P r i v ac y L a w s or a ny o t he r th ir d p a r t y r e q u e s t / en q u ir y i n r el a ti o n t o t h e P e r s o na l D at a . I R OS s h a l l r e s po n d t o th e a fo re m e n t i o ned o c c ur a nce s i n a cc o r d a n c e w i t h a p p l i cab le P r i vacy La ws and p r o vid e t h e C L I E N T w i t h s u c h in f orm a t i on and a s s i s t anc e w it h r e s p ect t o t h e a f o r e m t n i o e d o cc u r re n ce s a s t h e C L I E N T m ay r e asona b l y r e q ue s t . 2 2 . L I A B I L IT Y AN D I ND E M N I F I C A T I O N . 2 2 . 1 22.1 . 1 in r e spec t o f a n y in d e m n i f i ca t i o n o b li g ati on a ri s i ng p u r s u a n t t o t h i s Ag r ee m e n t; 22.1 . 2 in r e spec t o f f r a u d u l e n t mis r e p r e s e n t a t i on or f r au d ; 14 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N 2 2. 1 . 3 i n the e v e nt o f i n j u r y t o o r d e a th of , a ny p er s o n c a us e d b y its n e g l ig e n c e o r t h a t of i ts e m p l o y e e s o r a g en t s a n d fo r w h i ch it i s r e sp o ns i b l e ; o r 2 2 . 1 . 4 wh er e s uch l i m itati on or e x c l us i on w ou l d cont r aven e A p p l ic abl e La w s . S u bj e c t t o Cl a u se 2 2 . 1 , ne it h e r P a r ty s h a l l b e l i a b l e o r r e s pon s i b l e t o t h e o t h e r P a r t y f or a n y i nd i re c t or co n s e q u e n t i a l loss (i nc l u d i ng l o s s o f g o o dw il l , l o s s of p r of it, l o s s of any co n t r a c t, l o s s of o p p o r t u n i t y, l o s s of a n t i c i p a t ed pro fit s o r r evenu e o r c o s t s of c a p i t a l ) , and i n ea c h c a se ho w s oe v e r cau s ed w he t he r a r i s i n g u n de r c o n t r a c t, t o rt ( i n c lud i ng n e g l i g e n c e a nd b r ea c h of s t a tu t ory d u t y ) or o t he rw i s e, e v en i f it ha s be e n a d v i s e d o f t h e p o s si b i li t y o f s u c h los s . 2 2 . 2 2 2 . 3 S a v e a s p r ov i ded u n d e r Cl a u s e s 2 2 .4, C L I E N T s h all i n d e m n i f y, de f end a nd hold h ar ml e s s I R O S and it s A ff i l i a t e s , a g e n t s a n d S u bcon t r a c tor s f r om and a g ai n s t any L o s s e s s uf f e r ed a s a r e s u l t o f: 22.3 . 1 ad m i n i s tr a t i o n of t h e S t udy D r ug (i nc l u d i ng d ur ing t h e S tudy) , or t h e p e r fo r m a n c e of a ny p r oc e d u re r e q ui r e d by t h e Pro t o c o l fo r t he pe r f o r m a n c e o f t h e S t ud y , i n c o m p l i anc e w i t h t h e P r o t o c o l ( a s ap p r o v e d by C L I EN T a n d t h e r e le va nt Re g u l a to r y Autho r i t i e s ) ; 22.3 . 2 t h e S e r vi c e s i n f r i n g e s I n t e l l e c t u a l P ro p e r t y ; 22.3 . 3 22.3 . 4 C L I E N T ne g l i ge n c e , f r a u d or w i l l fu l m i s co n duc t in conne c t i o n w i t h t h i s Agr ee m e n t ; 2 2 . 3 . 5 C L I E N T CLIE N T da m a g e or L o s s e s t o t h e e x t e n t c a used b y 2 2 . 4 C l a u s e 22.3 . 1 t o 22. 3 .4 doe s n o t a p ply t o i n j ur y, l i a b i l i t i e s , : 22.4 . 1 fa i l u r e t o pro v i d e t h e S e rv i c e s a s r e q u i r e d p ur s ua n t t o a W O or t o a d he r e t o th e P ro t oco l (a s ap p ro v ed b y C L I EN T and t h e r e le v an t R eg u l a t ory A u t hor it i e s ) ; 22.4 . 2 f a i l u r e t o c om p l y w it h A pp lica b l e L a w s ; 22.4 . 3 ne g l i ge n c e , f r a u d o r w il l fu l m i s co n d u c t i n t h e p er f o r m a nc e of th e S erv i c e s ; o r 22.4 . 4 b r ea ch of i t s o b l ig a t i o ns unde r t h i s Ag r e e m e n t ( and / or a n y W O ) . 2 2 . 5 T h e C L I E N T i n Cl au s e 22.3 . 2 i s l i m i t ed t o t h e a m o u n t s a w a r ded i n f i na l j ud g e m e n t or ag r e ed i n s e tt l e m en t w i th t h e t hi r d p a r t y and t h e r ea s o n a bl e c o s t s a n d ex p e nse s in c urr e d by p r o p e r t y rig h t s i n f r ing e m e n t i n c o nn e c t i on w i t h t h i s A g r e e m e n t . 2 2 . 6 I R OS s h a ll ind e m n i f y, d e f e n d a n d h o l d ha r m l e s s C L I E N T and i t s A ff i l i a t e s , I n d e m n i fi e d P a r t y L o s s e s a r i s i ng o u t o f : C L IE N T 22.6 . 1 CLIE N T a nd t h e r e le v a n t Reg u l a t o r y A u t ho r i t i e s ); 22.6 . 2 Ap p lic a b l e L a w s ; 22.6 . 3 I R OS , fr a ud o r w i l l f u l mis c o n duc t in t h e p e rfo r m a nc e o f t h e S e rv i c e s a s r eq u i re d p u r s u a n t t o a W O ; o r 22.6 . 4 I R OS b r e ach o f i t s w a r ra n t i e s and r e p r e s en t a t i o ns unde r t h i s Agr e e m e n t ( an d / or a n y W O ). 15 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N 2 2 . 7 2 2 .5 d o e s n o t a pply t o i n j u r y, l i a b i li t i e s , d a m a g e o r L o s s e s to t h e e x t e n t ca u s ed b y: 2 2 . 7 . 1 C L I E N T 2 2 . 7 . 2 C L I E N T , f raud or w il l fu l m i s c o n d u ct i n t h e p e r f o r m a nc e of i t s o b l i ga t i o n un d e r t h i s A g r ee m e n t (and / or a ny W O) ; or 2 2 . 7 . 3 C L I E N T S u bj e c t to c la u s e 2 2 . 1 and w it ho u t p r e j udi c e t o c l a u s e 22 . 2 , t o t h e m a x i mum ex t en t p er mi t t e d un d e r A p plic ab l e L a w , the a g g re g a te lia b i l i t y o f ea c h P a r t y in r e s p ec t of a ny W O ( i n cl u di n g a s a n y s u c h W O m ay b e a m e nded by a n y a s so c i a t ed C O ) s h all n o t i n any ci r c um s t a n ce s wh a t s o e v e r ex c eed a g g r ega te a m o u nt s pa i d o r paya b l e by CL I EN T fo r p e r f o r m a n c e of t h e S e r v i ce s r e l a t ing t o s uch W O . 2 2 . 8 2 2 . 9 T his Cl a u s e 2 2 s h all r e m a i n i n f ull f o r c e a n d e f f e c t n otw i t h s ta n ding a ny t e r m i n a tion or e x p i ry o f t his Ag r ee m e n t. 2 2 . 10 Up on r e aso n a b le r e q u e s t b y I R O S or a n I n s t i t ut i on u ti l i z ed in c onnec t i o n w i th a W O , C L I E N T s h a l l execu te a n d pr o v i d e a s epar a t e l et t e r o f i n de m n i f i c a t ion t o I R OS t h a t c a n b e p r o v i d e d t o I n s t it u t i o ns, i n a f o r m m u t ua l l y a ccep ta b le t o th e P a rt i e s . 2 3 . I N D EM N I F I C A TI O N PRO C E D U R E . 2 3 . 1 T h e i n d e m n i f ica t i o n ob li ga t i on o f ea ch P a r t y u nde r Cl au s e 2 2 i s su b je c t t o t h e i n d e m n ifie d P a r t y n ot if y i ng t h e i n d e m n i f y i n g P a r t y a s soon a s p ra c tica b l e a f t e r beco mi n g a w a r e of t h e r el ev a n t c l a i m , a l l ow i ng t h e i nde m n if y i ng P a r ty t o t ak e c o n t r o l of t h e d e f e n s e a n d s ett l e m e n t o f t h e c l a i m , a nd ta k i ng a l l ac t i o n r easo n a b l y r e q ue s te d by t h e i n d e m n if y i n g P a r t y to a v o id, c om pro mise o r d e f end t h e c l a i m a n d a n y p r o c e e d in g s i n r esp e c t of t h e c la i m . Th e i n d e m n i f i e d P art y sh a ll p r ov i d e a ny s u p p o rt re a son a b l y r e q ue s te d by t h e ind e m n i f y i n g P a r ty t o d efe n d th e c la im . D I S C L A I M E R 2 4 . 2 4 . 1 CLIE N T ackn ow l ed g e s t hat : 24.1 . 1 th e r e s u l t s of t h e S e r v i ce s t o b e p ro v i ded a s o u t l i ned h e r e in a r e i n h e re n tl y u n c er t a i n an d t h at , ac c o r d i n g l y, the r e c a n b e n o a s s ur an c e , repr e s e n t a t i on or w a rr a n t y by I R OS t ha t t h e S t u dy D rug w i l l b e ap pr o v e d a n d / o r s u c c e s s fu l l y m a r k et ed by C L I E NT . 24.1 . 2 I R OS s h all n o t b e r e s po n s ib le for th e a u t he n t i c i t y or s u c c e s s f u l o u t co m e of t h e S t u d y Dr u g . 24.1 . 3 th e S e r v i c e s t o b e p r o v i d e d b y I R OS a s o u t l i ned he r e i n a r e b a s ed u p o n i n f o r m a t i o n supp li ed b y I R OS and C L I E N T , a s w e l l a s o t he r s , a n d t h a t I R O S doe s n o t g uaran t e e o r w a r ra n t t h e r e s u l t s of s u c h S e rv i c e s , w it h t h e excep ti on t ha t d a t a c o l l ec t ed in s u p p or t o f S tu d i e s , w i l l b e ac c u r a t e , l e g i b l e , r e l i ab le a n d s u i t ab le f or u s e i n t h e S tu d y and o t he rw i se in a c c o r da n c e w i t h t h e t er m s of t h i s A g r ee m e n t a n d a ny a p p l i c a b le W o r k O r d e r s . F o r t h e a v o i d a n c e of d ou bt, I R OS sha ll n o t b e r e s po n s i b le f or t h e a ccu rac y , c om ple t e n e s s , o r i n t eg r i t y o f a n y i n f orm a t i on, r eco r d s , or da ta s u p p l i ed by C L I E N T , I n s t it u t i o ns, or t h i rd p a r t i e s . 2 5 . T E R M OF A G R E E M E N T . 2 5 . 1 T h i s Ag r ee m e n t sha ll co mm e nc e a s o f th e E f f e c t i v e D a te a n d s h all co n t i n u e f o r th e In it i a l T er m f r om tha t da te, u n le s s e ar l i e r t e r m i na t e d by e i t h e r P a rt y in a cco r da n c e w it h C l a u s e 2 6 be l ow . 2 5 . 2 A t t h e e nd of t h e I n it i a l T er m , t h e P a r t i e s m ay e x t e nd t h e A g ree m en t b e yo n d t h e In it i a l T e r m for a d u r a t io n E x t e n d e d T e r m Ag r ee m e n t s i g ned b y b o t h P a r t i e s , a t l ea s t 1 5 ( f ift e e n ) d a y s pr i or t o th e e nd o f t h e I n i t ia l T er m . 16 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N 2 6 . T E RM I N A T I O N . 2 6 . 1 T h e P ar t i e s m ay dec i d e t o t e r m i na t e th i s A g r ee m en t by m u t u a l co n s e n t i n w r i t i ng w it hou t t h e need fo r a co u rt o r d e r . 2 6 . 2 I R O S m a y t e r m in a te this A g r ee m e n t or a ny W O und e r t h i s A g re e m en t w i t h o u t c au s e a n d w ith o ut the need f or a c o u rt o r de r a t a n y t i m e d u r i n g t h e t e r m of t h e A gre e m en t o n t h i r t y ( 3 0 ) days pr i o r w r i t t en n o t ic e t o CL I EN T . I R O S s ha l l re i m bu r s e th e C L I E N T f o r i t s r e a s o nab le a n d d i r e c t co s t s a nd e x p ens e s i nc ur re d by t he C L I E N T i n c o n n ec t i on w i th e n g a g i ng a n ew C R O s e r vi c e s p r o v i d e r f o l lo w i n g t e r m in a t i o n b y I R OS p ursuan t t o t h i s c l a u s e . 2 6 . 3 W O s c u rr e n t ly i n e ff e c t . 2 6 . 4 E i t h er P a r ty m a y t e r m in a te a ny W O in re l a t ion t o a S tudy b ef o r e t he b e g i n ni n g of s u c h S tu d y i m m e d i a t e l y by wr it t en no t i c e t o t h e o t h e r : 26.4 . 1 in t h e e v e n t of f a i l ur e by C L I E N T t o s e cur e a p p r o v al f r o m t h e r e le v a n t R eg u l a to r y A uth o r it i e s for the c ond u ct of the S tu d y; 26.4 . 2 th e S t udy can n o l o n g e r b e c on d uc te d d u e t o l oca l r e gul a t i o n s or gove r n m en t re s t r i c t i o ns ; 26.4 . 3 th e S t udy i s te r m i n at ed fo r a ny r ea s o n t ha t i s no t t h e fa u lt o f t h e t e r m i na ti n g P a r t y in c l u d in g d u e t o a s i gni fi c a n t c h an g e i n t h e s a m p le s i z e ga t he r ed i n t h e r e l e v a n t t e r ri to r y ( i e s ) i n co mp a r i s on to t h e s a m p le r equ ire m e n t s a s s e t ou t i n t h e P r o t o c o l wh ic h pr e v e n t s t h e S t udy f rom be ing s u cc e s s f u l l y c on d u ct e d ; a nd 2 6 . 4 . 4 in t h e e v en t t h at f o r w h a t e v e r r ea s on C L I E N T i s no l o n ge r th e s p o n s or o f t h e r e l e v a n t S t u d y , i n wh ic h c a s e n e i t he r P a r t y s ha ll b e l i ab le t o t h e o t he r P a r t y f or a n y Lo s s e s , c la im s , d a m a g e s , f e e s, l i a b i l i t i e s , co s t s or ex p e n s e s su f f e r e d or i nc ur re d by t h e o t h e r P a r ty on t h e a ccou n t of such t er mi na t i o n . 2 6 . 5 An y W O sha ll t er mi na te im m e di a t e l y u p o n w r i tte n n o t ic e o f o n e P a r t y t o t h e o t h e r , i f t h e r e l e v a n t R eg u l a t o r y A u t h or it i e s h a v e de c i d e d to t e r m i n ate th e c o r re s p on d i n g S t u d y du e t o a ny caus e r e l a t ing t o t h e s a fe t y of th e s u b je c t s or any e t h ic a l r easo n , in w h i c h c a se n e i t he r P a r ty s h a l l b e l i a bl e t o t h e o t he r s f o r any Loss e s , cl a ims, d a m a g e s , f ee s , l i ab il i t i e s , c o s t s o r e x p e n s e s s uf f e r ed or i n c ur r ed by t h e o t h e r o n t h e ac c o u n t of such t e r m i n a t i o n . 2 6 . 6 E ac h P a r t y s h all ha v e t h e rig h t , w i t h o u t pre ju d i c e t o i t s o t he r r i g h t s o r r e m e d i e s , i n cl u d i ng t h e r i g h t t o r eq u e s t f o r d a m age s, t o te r m i n a t e t h i s A g r ee m en t (a n d a l l r e l at ed W O ) i mm e d i a tel y b y wr i t t e n n o t i c e t o t h e o t he r 2 6 . 6 . 1 i f t h e o t h e r P a r t y ha s m a d e any f a l se m a te ri a l re p r e s en t a t i o n or w a r ra n t y i n t h i s A g r e e m en t ; 26.6 . 2 i f t h e o t he r P a rt y ( i ) su s p e n ds or t h r ea te n s t o su s p end, p a y m e n t of i t s de b t s or i s u nab le t o p ay it s d eb t s a s t h e y f a l l d u e or a d mi t s i nab i l i t y to pay i t s d e b t s , or ( i i ) beco m e s in s o l v e n t or a p e t it i o n i s f i l e d , a n o tic e i s giv e n , an o r de r i s m ad e or a r e s o l u t i on p a s s ed for t h e ad mi n i s tr a t i o n, w i ndin g - up or d i s so l u t ion o f t h e othe r P a rt y ( o t he rw i se t han f o r t h e p u r pose s of a s o l ven t a m a l ga m a t i o n or re c on s t r u c t i on ) , or (ii i ) an a p p l i ca t i o n i s m a d e t o c o u rt, or a n o r d e r i s m a d e to appo i n t a n ad mi n i s tr a t i v e o r o t he r r e ce i ve r, m a n a ge r, l i q u i d a t or , ad mi n i s tr a t o r, tr u s t e e o r simi l a r o ff ic e r ove r all or a n y s u b s ta n t i a l pa rt o f th e a s s e t s o f t h e o t he r P ar t y, or (i v) t h e o t he r P a r t y e n t er s in t o or p r opo s e s a n y c o m p o s i t ion o r arr an g e m e n t w it h i t s c r e d i t o r s gene r a l l y , or (v ) a n y t h in g an a logo u s t o th e f o r e g o i ng o c c ur s i n a ny ap p l i c a b le ju ri s d i c t i o n . 2 6 . 7 E ac h P a r t y s h all ha v e t h e rig h t , w i t h o u t pre ju d i c e t o i t s o t he r r i g h t s o r r e m e d i e s , i n cl u d i ng t h e r i g h t t o r eq u e s t f o r da m a g e s , to t e r m i n a t e a W O i m m ed i a t e l y b y w r it te n not i c e t o t h e othe r i f t h e o t he r P a rt y i s i n b r e ach of a ny o f i t s m a t e r i a l o b l i g a t i ons u n d e r th at W O or thi s A g r ee m e n t ( w i t h r e s p e c t t o t ha t WO ) a n d 17 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N e i t h e r t h a t b r each i s i n c a p a ble o f re m e dy or t he o t h e r P ar t y s h a ll h a v e f a i l ed t o re m e dy t h at b re ach w i t h i n 30 ( t h i r t y ) d a ys a f t e r r e c e ivi ng w r i tte n n otic e r e q u i r i n g it t o r e m edy t h a t br e a c h . 2 6 . 8 W it h o ut a ff ec t i n g a n y o t h e r r i g h t or r e m e dy av a i l a b l e t o it, I R OS m ay t e r mi n a te a W O w i th imme di at e e f f e c t by givi ng wr i t t e n n o t i c e t o t he C L I E N T : ( i ) i f t h e C L I EN T f a i l s to p a y any a m ou n t d ue un d e r t h a t WO on t he d u e d a te f or p a y m e n t ; (ii ) I R O S h a s e x e r c i s ed it s r i ght t o s u s p e nd t h e S er v i c e s und e r C l a u s e 1 5 . 4 . 1 a n d not i f i ed t h e C L I E N T o f it s i n t e n t ion t o t e r mi n a te the W O i f p a ym e nt i s n o t m ade w i thi n a f u rt h e r t hi rt y ( 30 ) d a y s ; ( i ii ) t he C L I E N T a n d r e m a i n s i n d e f a ult t h i rt y ( 30 ) d a ys a ft e r c omm e n c e m e n t o f t he s us p e n s i o n . 2 6 . 9 T e r mi n a t i o n of t h i s A gre e m ent o r o f a W O , a s a p plic a b l e , s h a l l b e e f f e ct i v e imm e d i a t e l y or o n the d a te s e t o ut i n a t e r m i n atio n n otic e a s t h e ca se m ay b e , w i t hout t he n e ed o f a c ou r t o r d e r. 2 6 . 10 I n t he e v e nt of n o t i c e o f te r m i n a t i on b e i n g g i v e n b y eit h e r P ar t y a s d e s c r i b e d a b o v e , t he P ar t i e s ag r e e t o co o p e r a te i n g o o d fa i t h i n r esp e c t of t h e tra ns i t i on o f o n g o i ng S e r vi c e s d u r i n g t he p e r i od of noti c e a n d t h e c l o s e - o u t p eri od r e f err ed t o i n Cl au s e 2 6 . 12 (w hi c h m ay e x te n d b e y ond t he e f f e c t ive d a t e of t e r mi n a t i o n ) . 2 6 . 11 O n e ar l y t e r mi n a t i on or e x p i r y of th i s Ag r ee m e nt o r a W O , a s ap p l i c a b l e : 26.11 . 1 the r i g hts g r a n t ed by o ne P a r t y t o t h e ot h e r u nd e r thi s A g r e e m e n t or the WO , a s a p p l i ca bl e , s h a l l cea s e ( ex c e pt a s ex pr e ss ly a ut hor ize d by t he o t h e r P a r t y f o r t r a n s i ti on pu r p ose s ) ; 26.11 . 2 each P a r t y s h all p ro mp t l y d e l i v e r to t he o t h e r o r d e s tr oy, u pon i t s re q u e s t, all Co n f i d e nt i a l I n f o r m ati o n , a n d , i n t h e c a se o f I R O S, all C L I EN T P r o p e r t y t h a t a r e i n i t s p os s e s s i on or u n d e r i t s c o nt r ol . No t w i t h s t a n di ng t he f o r eg o i n g, t he r ec e i vi ng P a r t y sh a ll be p e r mi t t ed t o r e tai n o n e c o p y o f Co n fi d e ntial In f o r m a t i o n a n d , i n t he c a se of I R O S , C L I EN T P r o p e r t y, t o t he e xt e nt r e q ui re d to c o m p l y w it h A p p l i c a b l e La w s ( in c l u d i n g t he r ul e s of a n a p pl i ca b l e s to c k ex c h a n g e ) or b o n a f i de i n t e r n a l d o c u m e nt r et e nti on p o l i c i e s a n d s h a l l n o t be r eq u i r e d t o d e s tr o y , d e let e , o r m o d i fy a n y b a ckup t a p e s or o t h e r m e d i a c o n t a i n i ng s u c h C o n fi d e n t i a l I n f o r m ati on or C L I EN T P r o p e rt y p u r s u a nt t o a u t om a t ed a r c h i v a l p ro ce s s e s in t he o r d in a r y co u r se o f it s bus i n e s s , pr o v i d e d t h a t s u c h Co nf i d e ntial In f o r m a t i on an d , i n t he c a se of I R O S, C L I EN T P r o p e r t y w ill not be u s ed o r a c c e s s ed f o r a ny o t h er pu r p os e and s h all r e m a i n su b j e ct t o t h e t er m s of t his A g r e e m e n t . 2 6 . 12 te r m i n a t io n n o t i c e in r e l a ti on to a WO f o r a n y r e aso n , t h e P a r t i e s s h a l l m ee t t o p r ep a r e a clo s e - o u t s c h e d u l e, a nd I R OS s h a l l c e a se p e r f o r m i n g a l l w o r k n o t n e ce s s a ry f o r t h e o rd e r l y cl o s e - o u t o f t h e S e r v i ce s or r eq u i r e d by l a w s o r r egul ati o n s . Ea c h P a rt y sh a l l c o mply w it h i t s o bli g a t i o n s i n t he a g r eed c l o s e - o u t S ch e d u l e fo r t he p e r i od r e f e r r e d to i n it ( w hi c h s h all be at l e a s t s ixt y ( 6 0) d a y s u n l e s s a s h o r t e r p e r i o d i s re q ui re d by t h e C L I EN T ) . 2 6 . 13 Un le s s ot h erw i se s t a ted i n t he n o t i c e of t e r m in a t ion, t e r m ina t i o n or ex p i ry of t his A gre e m e nt s h a l l n o t a f f e c t t he v a l i d i ty of any WO h e r e u n d e r th e n in ef f ec t , a nd a ll t he t e r m s of th i s Ag re e m e n t s h all s u r v ive and c o n t i n ue to a p p l y t o s u c h WO u n t i l i t s c o mpl e t i on or ter m i n a t io n . 2 6 . 14 I f thi s A g re e m e nt or a ny W O i s t e r mi n a t e d, C L I EN T sh a l l p a y I R OS f o r a l l S e r v i ce s p e r f or m e d i n ac c o r d an c e w i t h th i s A gr e e m e nt or any W O up t o t h e t e r m i n a ti on d a t e , p r o v id e d t h at I R OS h a s c om pl i ed w it h i t s o b l i g a t i o ns u n d e r t he Pro t o c o l and a n y P r o t o c ol i n h a n di ng ov e r any on g o i ng S t udy t o C L I EN T or a r e pl a c e m e n t C R O pro vi d e r . I f p aym e n t s a r e u n it or mi l e s t o ne b a s e d, a n d t h e A g r e e m e nt or a W O i s te r m i n a t e d a fte r a g r e e d co s t s h a ve b e e n i n c urr e d to w ard ac hi e v in g p or ti ons o f o n e or m o r e i n c om p l e t e un i t s or m i l e s t o n e s, C L I EN T w ill p a y I R OS t he a gr eed f ee s f o r a c t u a l wo r k p er fo r m ed t o w ard t hos e i n com p l e t e uni t s o r m i l e s t on e s u p t o t he d a t e o f te r m i n a t i o n , in ad d i t i on t o p ay i n g f o r c o m p l e te d u n i t s or m i l e s t o n e s . I f p a y m e n t s a r e u nit o r m i l e s t o ne b a s e d, and the Ag r ee m e nt or a WO i s te r m i n a t e d , C L I EN T w i l l o n l y be r eq u i r e d t o p a y I R O S f o r com pl e ted u ni t s o r mi l e s t o n e s . 2 6 . 15 An y te r m i n a t i o n o f t h i s A gr e e m e n t (ho w s o e v e r o c c a s i on e d ) s h a ll n o t a f f ec t a n y a c c r u e d r i g h t s or l i a b i l i t i e s of e i t h e r P a r t y, n o r s h a l l it a ff e c t t he co m i ng in t o f o r c e or t he cont i n u a n c e i n forc e of a n y p r o v i s i on of th i s A g r e e m e n t w hi ch i s e x p r e s s l y or by i m p l i cat i o n inte nd e d t o c o me i n t o fo r c e o r c o n t i n u e i n f o r c e on or a f t e r ter m i n a t i on . 18 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N 2 7 . N O T I C E A N D D E L I V E R I E S . 2 7 . 1 An y n o t i c e r e q u ire d o r pe r mit t ed t o b e g i ven h e r e u n d e r by e it h e r P a r ty he r e u n d e r s h a l l b e i n w ri t i ng a n d s h a l l b e dee m e d g i ven on t h e d a t e r e c e i ved i f de l i ve r e d p e r s o n a l l y o r by a r e p u t a b l e o v e r ni g h t de l i v er y s erv i ce , o r s e v en t y - t wo ( 72 ) hours a f ter t h e d ate p o st m a r k e d if s e n t b y reg is t e re d o r c e r ti f i e d m a il, r et u r n r ec ei p t r eq u e s te d , p o s ta g e p re pa i d t o t h e phy s i ca l ad d r e s s , or on t h e d ate of t h e e m a il i f s e n t b y e m ail t o t h e e m a i l ad dr e ss e s s e t o u t f or ea c h P a rt y i n th e Co n t r ac t P a r t i cu l a r s . 2 7 . 2 I f CL I E N T d el iv e rs , s h ip s , o r m a ils m a te r i a l s or d o cu m e n ts t o I R OS, or r e q u e s t s th a t I R O S d e liv e r s, s h i p s , o r m a il s m a t e r i al s o r do c u m e n t s t o CLIE N T or t o t h i rd par t i e s , t hen t h e e x p e n s e and ri sk of lo s s f o r s u c h de l i v e ri e s , s h i p m en t s, or m ai l i n gs s h all b e b o r n e by C L I EN T , p r o v i d e d t h at I R O S f o l l o w e d CLIE N T w r i t t e n i n s t ruc t i o n s f or t h e m a t e ri a l s t ha t w e r e d e l iv e r e d , s h i p pe d, or m a i l e d . I R O S di s c l a i m s any lia b i l i t y f o r t h e a c t ions o r o m i s s i o n s of t h i rd - pa rt y de liv e r y S e r vic e s o r c ar r i e r s . 2 8 . I N D E P E ND E N T C O N T R A C TOR R EL A T I O N S H I P . 2 8 . 1 F o r t h e pu r p o s e s o f t hi s Agr e e m e n t , t h e P a r t i e s h e r e to a r e i n d e p en d e n t c o n t r a c t o r s a n d no t h i n g co n t a i n e d in t h i s A g r ee m e nt s h a l l b e c o nst r u e d to c o n st i tut e , c r ea t e , or in a ny w a y be i n t e r p r e t e d a s , a joi n t v en t ur e o r pa r t n e r s hip be t w een t h e P a r tie s . 2 9 . S U B C O N T R A C T I N G . 2 9 . 1 A s p a r t of t h e S erv i c e s , i f s e t fo rt h i n a W O , I R OS m ay e n g a g e a t h ir d - pa rt y p r o v i d e r f o r th e p r ov i s i on of S e r vi c e s wh ic h a r e e i t he r i ) n o t c u s t o m ari l y per f o r m ed b y I R O S , or ii ) r eq u i red to b e p e rf o r m e d i n te rr i t o r i e s o u t s id e of t h e U A E wh e r e I R O S d oe s n o t c u s t o m ari ly o p er a t e ( a S u b co nt r a c t o r ) . I R OS w i l l s ecur e t h e w r it t en a p p r ova l of C L I E N T to e n ga g e a S u b c o n tr a ct o r w h ic h w i l l n o t b e u n r e a s ona b l y w it h h el d . I R O S s h all r e m a i n f u l ly re s p o ns i b le f or t h e pe rf o r m a n c e by i t s Su bco n t r a c t o r s of any S e r v i ce s a s i f it had p e r f o r m ed t h e S e r v i ce s it s e l f . I R O S ' s du t y w i t h r e spec t to s u c h Su b c o n tra c to r s s h all b e t o co o r dina te t h e i r a c t iv it i e s a nd t o m a k e t h e c o r r e spond i ng p a y m en t s , a f t e r r ec ei p t of suff i ci en t f u n ds f r o m CL IE N T , i n a cco r dan c e w i t h t h e r el e v an t W O . F o r t h e p u r p o s e s o f c la r i t y , a n I n s t it u t i o n c o n d uc t i ng a S t u d y p u r s uan t t o a C l i n i c a l Tr i a l A gr e e m e n t i s n o t a S u b c o n tr ac t o r of I R OS f o r t h e pu r p ose s o f t h i s Ag r ee m e n t or a W O . 3 0 . B I N D I N G A G RE E M E N T AN D A S S I G N M E N T . 3 0 . 1 T h i s Agr e e m e n t sha l l b e b i n d i ng u pon and i n u r e t o t h e be n ef i t of C L I EN T and I R O S and t h e i r r e s p e c t iv e s u c ce s s or s a n d pe r m i tte d a s s i g n s . 3 0 . 2 E x c e p t pu r s u a n t t o Cl a u se 2 9 ( S ub c o n tr a ctin g ) o r i n t h e ca s e of : 3 0 . 2 . 1 an a s s ign m e n t to a n A ff i liate o f t h e P a r t y ; o r 30.2 . 2 in c o n n e c t i o n w i t h th e m e r g e r , c o ns o l i da t i o n o r s a l e o f s ub s t an ti a l l y all of a P a r ty a s s e t s r e lat ed t o t h e S t u d y , ne it he r P a rt y m ay a s s i g n , t r a n s f e r , c h ar g e o r d e a l i n a n y o t h e r m a nn e r w it h a n y of it s r i g h t s or o b l iga t ions u n de r t h i s A g r e e m e n t w it hou t t h e p r i o r w r i tte n c o n s e n t of th e o t h e r P a r t y. 3 0 . 3 I f I R O S h a s t r a n s f err e d ri g h t s an d / or ob l i g ati o n s unde r t h i s A g r e e m en t pu r s u a n t t o Cl a u se 30 . 2 . 2 and t h e CL IE N T ob j e cti o n s t o t h e i d e n t it y o f t h e a s s i g n e e on th e b a s i s t ha t it i s a c o m pe t i t or of th e C L I E N T o r t h e CLIE N T ha s r e a s o n a b l e g r o u n d s t o be l i e v e th at t h e a s s i g n e e i s no t f i n a n c i a l l y s o u n d, doe s n o t h a v e t h e r e s ou r c e s of c a p ab il i t y t o co m p l y w i t h t h i s Agr ee m en t o r p r e s en t s re p u t a t i o n a l , r eg u l a to ry o r o p e r a t i o n a l r i s k t o t h e CLIE N T , t h e CLIE N T m ay ter mi na t e t h i s Ag r ee m e n t on wr it t en n o t i c e t o I R OS and t h e a s s i gnee . 3 0 . 4 T h e P a rt i e s ac k n o w l e d g e a nd a g r e e t ha t : ( i ) t h i s Agr ee m en t ha s been en t e re d i n t o i n con te m p lati on of t h e i nco r po rati on of a n op e r ati ng s u b s i d i ary o f t h e C L I E N T i n t h e U ni t e d A r ab Em i r a t e s t o s p o n s or t h e S t u d i e s i n t h e U n i t ed Ar ab E m i r at e s ; and ( i i ) imm e d i a t e l y f o l lo w i n g i n c o r p o r a t i on, t h e C LIE N T sha ll t r a ns f e r al l o f i t s r i g ht s a n d o b l i ga t i o n s u n d e r th i s Agr e e m e n t t o s uch s u b s i di a ry ; a nd (ii i ) t h e P a r t i e s s ha ll 19 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N e x ec ute ( a n d the C L I E N T sh a l l p r o c u r e e x e c u t i o n b y t he s u bsidi a r y o f ) a ny d o c u m e n t s n e c e ss a r y t o give e f f e c t t o s u c h tra n s f e r. 3 1 . GO V E R N I N G L A W . 3 1 . 1 T his Ag r e e m en t a nd a ny d i spute o r cl a i m ( i n c l u d i ng no n - c o n t r a c t u a l d i s p ut e s o r c la ims) s h a ll b e co n s tr ue d, g o v e r n e d, i nt e r p r e t e d, and a pp li ed i n ac c o r d a nc e w i t h t h e l a w s of t h e A b u D h a b i G loba l M a r ke t . 3 2 . S E V E R A B I L IT Y . 3 2 . 1 I f an y p r o v is ion or p a r t of a p r o v i sion of t h i s A g r ee m e nt i s d e c l a r e d in v a l i d, i l l e g a l , or un e nf or c e a b l e , t h e i nva li di t y , i l l ega l i t y, or u n e n f o r c e a b i li t y t he re o f w i ll n o t a f f ec t t h e r e m a i n in g pa rt of t ha t p ro v i s i on a nd a l l o t he r p r o v i s i o n s of t h i s A g r e e m e n t . 3 3 . V A R I A T IO N 3 3 . 1 S u bj e c t t o Cl a u s e 2.6 , no v ari a t i on o f t h i s A gr e e m e n t s ha ll b e e f f ec t i v e u n le ss i t i s i n w ri t ing a nd s i gned by t h e P a rt i e s ( o r t h e i r au t hor i s ed r epr e s e n t a t i ve s ) . 3 4 . W A I V E R . 3 4 . 1 F a i l ur e or de l a y by a P a r t y t o e xer c i s e a n y r i g h t or r e m e d y p r o v i d e d u n d e r t h i s Ag r ee m e n t o r by la w sh a l l n o t c o n s t it ut e a w a i v e r of t h at o r any o t h e r ri g h t or re m e d y , n o r s h a l l it p r e v e n t or r e s t r i c t a n y f u r t h e r exe r c i se o f t h at o r any o t he r r i g h t o r r e m e d y . 3 4 . 2 A w a i ve r o f a n y rig h t or r e m e d y unde r th i s A g r e e m e n t or by l a w i s o n l y e f f e c t i v e i f g i v e n i n wr it ing a n d s h a l l n o t b e d e e m e d a w a i ve r o f a n y s u b s e q uen t ri gh t o r r e m e d y . 3 5 . S U R V I V A L . 3 5 . 1 O n t e r m i na t i o n o r e x p i r y of t h i s A g r e e m e n t , all ex i s ti ng W O s h a ll c o n ti nu e un l e ss e x p r e s s l y t e r mi na t e d a s pe r t h e r e qui r e m en t s o f Cl a u s e 2 6 . 3 5 . 2 An y p r o v i s i on of t h i s A g re e m e n t t ha t exp r e s s l y o r by i m p li c a t i on i s i n t e n d e d t o c ome i n t o or c o n t i n u e in f o r c e on or af t e r t e r m i n ati on or e x p i r y o f t h i s A g r ee m en t s h all r e m a i n i n f u ll f o r c e a nd effe c t. 3 6 . D I S P U TE R E S O L U T I O N . 3 6 . 1 I n t h e e v en t of a n y d i s pu te or dif fer e n c e b e t w e e n t h e P ar tie s a r i s ing ou t o f or i n c o n n e c t i o n w i t h or r e l a t i n g t o t h i s A gre e m en t o r a ny W O ( a " D i s p ut e" ), e i t h e r P a rt y s h a l l g i v e t o t h e o t he r wr i t t e n n o tic e o f t h e D i s p u te, s et t ing o u t it s na t ur e and f u ll p a r t i cu l ar s ( a d o cu m e n t s. O n s e r v ic e o f t h e D i s p u t e No t i ce , t h e i n g o o d f ait h t o r e s o l v e t h e D i s pu t e . ), t oge t he r w i t h r el ev a n t s u p p o rtin g s h a l l a tte mp t 3 6 . 2 te n ( 10 ) c a l e n da r days of r ec ei p t of t h e D i s p u te N o t i c e , t h e D i s p u te s ha ll b e r e f e r re d i n w r i ti ng t o t h e A m i r H e s h m a t p our of t h e CL IE N T a n d t h e C h i e f Exe cuti v e O ffic e r of I R O S . T he s e r e p r e s e nt i ve s s h all, w i t h i n t e n ( 1 0 ) c a l en d a r d a y s o f t h e r e f e rr a l o f t h e D i s p u t e , ho l d a m e e t i n g ( a "D i s p ut e M e e t i n g ") e i t he r in pe r son o r v i r t ua l l y in an e f f o rt t o r e s o l v e t h e D i s p u t e . 3 6 . 3 An y D i s p u te wh ic h i s n o t r eso l ved w it h i n t h i r t y ( 3 0 ) c a l end a r d a ys a f t e r th e s e rv i c e o f a D i s p u te N o tic e , wh e t h e r or n o t a D i s p ut e M ee t i ng ha s be e n h e l d , m ay b e s u b mit t ed by a P a r t y t o th e c o u r t s o f Ab u D h a b i G l o ba l M a r ke t , i n t h e E mi rate of Ab u Dh a b i, U A E , wh ic h s h a l l hav e e x c l u s iv e j u r i s d i c t io n to d e cid e o n any d i sput e a r i s ing our or i n c on n ec t i on w i t h t h i s A g ree m en t and a ny W O . 20 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N 3 7 . E N T I R E A G R EE M E N T AN D M O D I F I C A TI O N . 3 7 . 1 T h i s A gre e m e nt , t o g e t h e r w i t h t h e W O and C Os , co n t ains t h e en ti r e u n de r s t a n d i ng of t h e P a rt i e s w i t h r e s p ect t o th e su b j ec t m a t t e r he r e i n, a n d s u p e r s ede s all p r ev i o u s a g r ee m e n t s ( o r a l a n d wr it t e n) , l e t t e r s of int e nt, n e g otia tions a n d d is c u s sion s . A ny m o di f ic a tions t o t h e pr o v i sio n s h e r e i n m u s t be i n wr i t i ng a nd s ig n e d by t h e P a rt i e s . 3 8 . TH I R D P A R T Y R IG H T S 3 8 . 1 U n le s s i t e x p r e s sly s tat e s ot h e rw i s e , this a gree m e nt d o e s n o t g i v e r is e t o a n y r ig h t s ( w h e t he r st a t utory or o t he r w i s e ) t o a ny t h i r d pa r ty w h o i s n o t a p a r t y to t h i s a gr e e m en t to e n f or c e a n y t e r m o f t h i s ag r e e m e n t . 3 8 . 2 T h e r i g h t s of t h e pa rtie s t o re s c ind or va r y t h i s a g r ee m en t a r e n o t su b je c t t o th e c o n s en t o f any o t he r p e r s on. 3 9 . C O UN T E R P A R T S. 3 9 . 1 T his A gre e m e n t, a W O a n d / o r a CO m a y be e x e c u t e d i n a n y n umbe r o f c o u nt er p a r ts ea c h o f w hi c h, w h e n execu t e d, s h all c o n s t i t u te an o ri gina l, b u t a ll t h e c o un t e r p art s t oge t he r s ha ll c on s t it u te a s i ng le b i n di n g le g a l d oc u m e n t . T h i s Agr ee m en t m a y b e e x e c u t ed th ro u gh t h e u s e of a n e l e c t r o n i c s i g na t u r e . T r an s m i s s i on o f t h e e x e c u te d s i g n a t u r e p a g e o f a c o u n t e r p a r t o f th i s A g r e e m e n t b y ( a ) f a x or ( b ) e m a il ( in PD F , JP E G or othe r ag r e ed f o r m at ) t o a noth e r P a r t y s h all t a k e e f f e c t a s d e l i v e r y o f a n e x e c u te d co u n te r p a rt of t h i s A gr e e m e n t . I f e i t h e r m e t h o d of d eli ve r y i s a d o p t e d , w i thou t pr ej u di c e t o t h e va l i d i t y of t h e Agr e e m e n t t h u s m a d e , ea ch P a r t y s h a l l p r ovid e t h e o t h e r s w i t h t h e or i g i n a l of s u c h c o u n t e r p art a s s o on a s rea s o n a b l y p o s s i b l e t he r ea f te r . N o coun t e r par t s ha l l b e e f f e c ti v e u n t i l ea c h P a r t y h a s e x e c u te d and d e l i ve re d a t l ea s t o n e c o u n te rpart . S i g n a t u r e C l a u s e f o llo w s. 21 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N I N W I T N E SS WH E R E OF , D U L Y A U T H OR I Z E D R E P R E S E N T A T I V E S O F TH E P A R T I E S H A V E E X E C U TE D A N D D E LI V E R E D T H I S A G R E E M E N T , I N D U PL I C A T E , A S O F T H E EF F E C TI V E D A T E . A CK N O W LE D G E D , A C C EP T E D A N D A G R E E D T O : N E O N C TE CH N O L OG I E S H O L D I N G S , I N C . I N S I G H T S P H A R M A C E U T I C A L R E S E A R CH L L C By: B y: N a m e : T i t l e : T i t l e : D a t e : D a te : 3 October 2025 22 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G 4 October 2025

E X E C U T I O N V E R S I O N S C HE D U LE 1 D E F INI T I O N S A N D I N TE R P R E T A T I O N D ef i n e d T e r m s Aff i l i a t e m ea ns a ny p e r son di re c t l y C o nt r o l ling, C on t r o l l e d by or und e r d i r ec t o r i n di rec t C o nt r ol w i t h s u c h P ar ty ; A ff i l i a t e o f I R O S m eans M u b ada la I n v e s t m e n t Co m p a ny P JSC and G r oup 42 H o l d i ng Lt d a n d ea c h o f t he i r Con t r ol l e d e nti t i es, p r o v i d e d t h at f o r all p u r pos e s h e r e of , M u b a d a la Ca pital L L C , A b u Dh ab i I n v e stm e nt C o un c i l PJ S C or a n y t h ir d par t y c ap i t a l m ana g e m e n t f u n d s and t he i r re s pec t i v e d i r e ct l y a n d i n d i r e c t l y C o n t r o lle d s u b s i di a r ie s, a cco u n t s, col l e cti v e i n v e s t m en t f u n ds, i n ve s tm e n t h o l d i n g c o m p a n i e s or o t he r s im i l a r e n t i t i e s Con t r o l l e d , m a n a g e d or a d v i s e d by a ny o f th e m s h a ll n ot b e d ee m e d to b e a n A f f i l i at e of I R O S ; Ag r ee m e n t m eans t h i s a gr e e m ent ; A n o n y m i ze d D a t a m eans a n y dat a t h at h a s been i r r eve r s i b l y an o n ym i zed t o e x c l u d e i den t i f y i ng inf o r m a t i on r e lat ed t o a n a t u r al p er s o n a nd a n y o t he r i nf o r m ati on t h a t c o n s t it u te s P e r s o na l D a t a , w h i c h w ill b e p r o v i d e d b y I R O S to C L I E N T i n re l at i o n t o a S t u dy s ubj e ct ; A p p l i c a b le L a ws m eans any s u p r a - na ti ona l, f e der a l , na t i ona l, s tat e , m u n ici pa l o r l oca l s t a t u t e , la w , o r d i nance , r eg u l a t ion, r u l e , c o d e , orde r o r any o t h e r o rd e r o r j udg m e n t i s sue d , p r o m u l ga te d b y a ny G o v e rn m e n t a l En t i t y or any ru le or r equi r e m en t of a ny na ti ona l s e c u ri t i e s excha n g e , a s a n y o f t h e f o r e g o in g m a y b e a m en d e d f ro m t ime t o t i me and w h ic h a r e a p p l ic a b l e to a P ar t y or t o t h e sub je c t m atte r o f th i s Ag re e m e n t , in c l u d i n g P r i va c y La w s a n d Go od C l i n ical P ra c t ic e s ; B a c k g r o un d I P m eans i n r el a t i on t o a P a r t y , any In telle c t u a l P r o p e r t y, k n o w - h ow , i n f o r m ati on a n d m at e rial s (i ) o w ned b y o r lic en s e d t o t h at P a r t y o r i t s Af f i liat e s , p r i o r t o t h e c o m m enc e m e n t o f t h e A g r e e m e n t o r a W O (i i ) c r ea t ed d ur i n g t h e te r m o f t h e A g r e e m en t or W O b u t o u t s i d e t h e s c o p e of i t s a c t iv i t i e s u n d e r t h e S t u d y , a nd w h ic h a r e u s ed by s u c h P a rt y i n r e lati on to t h e S t u dy or t h e S e r v i c e s or ar e o t he r w i se m ad e a v a i l a b le t o t h e o t h e r P art y i n c o n n e c tio n w i t h t h e S t udy or S e r v ic e s . I t i n cl u d e s a n y i m p r ove m e n t s t he r e t o, w i thou t u s i ng or re fer enc i ng a n y ; C L IE N T I n d e m n if i e d P a r t y ha s t h e m e a n i n g g i ven t o i t i n C l a u s e 2 2 ; C li n i c a l T r i a l A g r e e m e n t s h all m e an t h e c o n t r a c t ua l a gr e e m e n t t ha t h a s b e en or w ill b e e n t e r ed i n t o b y C LI EN T and I R O S w i th a n I n s t i t u t ion f o r t h e con d uc t o f a S t udy by t h at I n s t it ut i o n ; C O ha s t h e m e a n i ng g i v e n t o i t i n C l a u se 2 . 6 ; C o n f i d e n t i a l I n f o r m a t i o n m e ans a l l s u c h in f orm a t i o n di s c l os e d pu r s ua n t t o t h i s A g r ee m en t an d / o r a W O , w he t he r f u r n i s h e d b e f o r e o r a fte r t h e d a t e h e r e of , w he t he r or al o r w r i t t e n , i nc l u d i ng t h e ter ms of t h i s Agr e e m en t . Co n fi dent i a l I n f o r m ati on m a y i n cl u de , bu t no t b e l i mi t ed t o, fi na n ci a l i n fo r m a t i on, kno w - h ow , tra d e s e c r et s, r e s e a rch ach i eve m e n t s , pr o duc t i o n m e th o ds, te c h n i q u e s , q ua l i t y c ont r o l, t e s t i ng m e t h o d s, s o ft w a r e , c ha rt, p r o g ra mm i n g spec ific a t i o ns, d eve l o pm en t p r o c e s s e s , s t e p s , i de a s, i nt e l le c t u a l p r o p e rt y (w he t h e r o r n o t re g i s t e r e d or p a t e n t e d ), b u s i ne s s p l an s , c u s t om e r l i s t s (p o t en t i a l o r e x i s t in g ), and o t he r i nfo r m a t i o n re l a ted to c u s t o m e r s , m a r k e t ing s trat eg i e s, th e te s t vac ci ne s , a n d o t h e r bu s i ne ss i n f o r m a t i on t h a t a r e d i s cl o s e d b y e i t h e r P art y ( or i t s A ff i l i a t e s ) fo r u s e i n o r i n c onnec t i on w it h t h e A g r ee m e n t a n d/or t h e S t u di e s . Conf i d e n t i a l I n f o r m a t i on doe s n o t i nc l u d e any inf or m a t i o n wh i c h t h e r e ce i v ing P a r t y can rea sona b l y d e m o n s trate t h at (i ) w a s l a w f u ll y k n o w n t o t h e r ec ei v i n g P a rt y p r ior t o r ec e i ving t h e s ame w i t h o u t r e s t ricti on a s t o u se o r d i s c l o s ure ; (ii ) i s or be c o m e s ge n eral l y ava i l a b l e t o t h e p u b lic ( t h r o u g h n o b re a ch o f t h i s A g r e e m e n t ) ; ( i i i ) w a s o b t a i ned by th e rec e i v i ng P ar t y f r o m a t h i rd p a r t y fr e e of any o b l i g at i on o f c o n f i den tial i t y a t t h e t im e of di s cl o su r e ; ( i v) i s re q u ire d t o b e di s c l os e d b y la w or r e gu l a t i o n ; C o n t r a c t P a r t i c u l a r s m eans t h e C o n t ra ct P a r t i c u l a r s s e t ou t i n t h e f ron t - e n d of t h e A g r e e m e n t ; C o n t r o l m eans t h e p o w e r t o d i re ct t h e m a n a g e m e n t a n d po li c i e s o f a per s o n, d i re c t l y or i n d i re c tl y, wh et h e r t h r ough o w ne r s h i p o f v o t i ng s ecu ri t i e s, by c o n tra c t o r o t h e r w i s e ; C R O ha s t h e m e a n i n g g i ven i n th e R e ci t a l s ; 23 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho g a n Lov e l l s K G G

E X E C U T I O N V E R S I O N E ff ec t i ve D a t e m e a ns the d a t e s e t o ut in the la s t sig n a tu r e in r e s p ect o f t his A gr e e m e n t i s r ec ei v e d ; E x t e n d e d T e r m ha s t h e m e a n i n g giv e n t o it i n C l au s e 2 4 ; F o r c e Ma j e u r e m eans a n y e xt e rna l e v e n t beyond t h e c o n t ro l of a P a r t y , i nc l u d i n g b u t n o t lim i t ed to, f lo o d, d r oug h t , e a r t hqua k e or o t h e r n a t u r al di s a s t e r ; t e r ro ri s t a t t a c k, c i v il w a r, c i v il co m m o t i o n , p a n de mic o r e p i d e m i c , or r i o t s , w ar , a r m e d c on f l i c t , i m p osit i o n of s an c t i o n s , e m b ar g o , o r b r e ak i n g o f f of di plom at i c r e l a t i o n s ; or a n y l a w or any a c t ion ta k e n by a G o v e r n m e n t a l E n ti t y , i nc l u d i ng w it ho u t l i m itati on im p o s i ng a n e x p o rt o r i m po rt r e s tricti o n , q u o ta or pr o h i b i ti o n , w h i ch a r e n o t r ea s o n a b l y fo r e s e ea b le ; G e n e r a t e d D a t a m eans all d a t a r e lat ed t o o r a r i s ing ou t o f t h e c o ndu ct of e a c h S t u d y , inc l uding r e s u l t s, c o n cl u s i o n s , dis c o v e r ie s , d e ta i l s , summa r i e s or co p i e s o f i n f o r m a t i o n, m at e r i a l s , a nd d o c um e nt a t i o n b ut e x c l u d i n g a ny I R O S B ac k g r o und I P ; G o o d C l i n i c a l P r a c t ice s m e a n s curr e n t g o o d c l in i c a l pr a c tic e s g u i de l i n e s of t h e In t e r na t i o na l C on f e r e n c e o n H armoniz a t i on of Tec h n i ca l R e q ui r e m e nts for Re g is t r a tion of P h ar m a c euti c als f or H u m a n U se To p ic E 6 : Gu i de l i ne s o n G o od Cli n ic a l P rac t ic e, toge t he r w i t h s u c h o th e r G o o d C l i n i c a l P r a c t i c e req u i r e m e n t s a s m ay ap p ly w it h i n t h e Te rri t o ry or such o t he r te r ri t o r y wh e r e a S tudy i s b e i n g c o n duct e d, 2 0 0 8 s e t f o r th in th e H el s i n k i D e c l a r ati on of t h e Wo rl d M e d ic a l C o n g r e s s, a n d a l l i mp o r t a n t g u id i ng pr i nc i p le s r e lat ed to d r ugs a n d cli ni cal t r i a l s t h at t a k e e f fe ct im m ed i a t e l y ; G o v e r n m e n t a l E nt i t y m eans a n y co u rt, a dm i n i s tr at i v e bod y , l oca l a u t ho r i ty or o t h e r g o ve r n m e nt a l o r q u a s i - g o ve r n m en t a l en tit y w i t h c o m p e t en t j u ri sd i c t i o n , a n y s u p r a - na ti onal , n ati o n a l, fe de r a l, s t a te, m u n ici pa l, p r ovin c i a l or l oc al g o ve r n m en t a l , re g u l a t o r y o r a d mi ni s t r a t iv e a u t ho r it y, a g enc y, c ommi s s i o n , c o u r t , t r i b una l, a rb i tr a l b o d y, s el f - r e g u l a ted e n t i t y, p r i v a te b o d y e x e r ci s i ng any r e g u l a t o r y , t ax i ng, i m p or t i ng or o t he r g o v er n m en t a l or q u a s i - g o ve r n m en t a l au th or it y or oth e r g o v e r n m e n t al e n t i t y, i nc lu d i ng any r el eva n t Reg u l a to r y A u t h o r i t y ; I n i t i a l T e r m ha s t h e m e a n i n g g i ven t o it i n in t h e C o n tra c t P ar tic u l a r s ; I n t ell e c t u a l P r o p e r t y m eans pa t e n t s , u ti l i t y mo de l s , r i g h t s t o i n v en ti ons, c o p y ri g h t a nd n ei g h b or i ng and r e lat ed r ig h t s , t r a d e m a r ks, bu s i n e s s n a m e s a nd do m a in n a m e s, r i g h t s i n g e t - up a n d t r ad e dr e s s , good w i l l a n d t h e r i g h t t o s u e for p a ss i n g o f f , r i g h t s i n de s i g n s , ri ght s i n c o mp u t e r s o f t w a r e, d a t a b a s e r ig h t s , r i g h t s t o u s e , a n d p r o t ec t t h e co n f iden tiali t y of, c o n fi den t i a l i n fo r m a t ion (i nc lu d i ng k no w - h ow and t r ad e s ec ret s ) , and a l l ot h e r i n t e l l ec t u al p r o p e r t y ri g h t s , i n e a c h c a se w h e t h e r r e g i s t e r ed o r u n r e g i s t ered a n d i nc l u d i ng all ap p l i ca t i o n s a n d r i g h t s t o a p p l y f o r a nd b e g r an te d, re ne w al s o r ex te n s io n s o f, and r i g h t s t o c la im p ri or it y f r o m , a ny r i g h t s a n d a ll s i m i l a r o r eq u i v al en t rig h t s o r for m s o f p r o t e ct i on th at s u b s i s t o r w ill s u bs i s t now o r i n t h e f u t ur e i n a n y pa rt of t h e wor l d ; I n t ell e c t u a l P r o p e r t y R i g ht s m eans r ig h t s s u b s i s t i n g i n t h e I n t e l l e c t ua l P r o p e rt y ; I n s t i t u t i o n m eans any i n s t i t u t i on a p p o i n te d by C L I E N T t o de s i gn a n d c o n d u ct a S t u dy a t a S t u d y s i t e ; I n v e s t i g a t o r s m eans t h e i ndiv i d ua l( s) ap p o i nted by t h e I n s t i t u t i on a n d i s re s p o ns i b le f or th e co n d u c t o f a S t u d y a t S i t e s I R O S P e r s o n n el ha s t h e m e a n i n g g i ven t o it i n C l a u se 3 ; L o s s e s m ean s , c o l le c t iv e l y, a l l l o s s e s , d a m a g e s, lia b i li t i e s, r ea s o nabl e a tt o r n e y fe e s, c o ur t c o s t s , and e x pen s e s ; P e r s o n a l D a ta m eans m e an a n y i n fo r m a t i on r e la t i ng t o a n i d e n t i fi ed or i d e n t ifia b le na t u ral per s o n a n d any o t he r i n fo r m a t i on t h a t c ons tit ut e s pe r s o nal l y i d e n t i fi ab le i nfo r m a t i o n u n de r a ny P ri v a c y L a ws . T h i s w i l l i nc l u d e n um ber , and pr o t e c t e d h ea l t h i nfo r m a t i o n ; P r i v a c y L a w s m eans a l l A p p li cab le La w s r el a t ing t o p r i va c y and P e r s o na l D a t a prot e c tio n i n t h e UA E , i nc l u d i n g F e d e r al L a w by D e c r e e N o . 45 of 2 0 2 1 on t h e P ro te c t i o n o f P e r s o na l D a ta a n d t h e E x e c u t i v e R eg u l a t i o ns r e lati ng t o i t, F e d e r al L a w N o . 2 of 2019 o n t h e U se o f t h e I n f or m a t i on a n d C o m m u n ic a ti on Tec h no l o g y i n H e a lt h F iel ds and Ca b i n et D ec i s i o n No . 3 2 / 2 0 20 on t h e I m p l e m e n t i ng Re g u lati on of F e d e r a l L a w N o . 2 of 20 1 9 and M i n i s t e r i a l R e s o l u t ion N o . ( 5 1 ) o f 2 0 2 1 on C a s e s w he r e H ea l t h D a t a and I nfo r m a t i o n m a y b e s t or ed or t r a n s f err e d o u t s i d e t h e S t a t e , a s a m e n ded fr o m t i me t o t i m e , and any o t h e r r e l e van t j ur i s d icti o n , i n cl u d i ng th o se r el a t ing s p e c ific a l l y t o s u b ject i nf or m a t i o n a n d co n s e nt ; 24 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N P r o t o c o l m ea ns a ny St u d y p ro to co l a t t ac h e d to t h e r e l e v a n t W O ; R eco r d s m eans da ta r ec o r ds p e r t a i ning t o t h e S e rv i ce s p e r f o r m e d ; R e g u l at o r y A u t h o r i t y m ea n s a n y i n t e r na ti ona l, na t i o na l , o r o t h e r g o v er nm e n tal, reg u l a tor y, or a d m in i s t r a t i v e au t h or i t y , or ot h e r b ody c o m p e t e n t t o g r a n t a p pro v al s , r e g i s t r a t io n s , or o t h e r c o n s en t s f or t h e co n d u ct of cli n i c al t r i a l s or f o r t h e m a nu f ac t u r e , i m p o r t a t ion a nd d i s t rib u t ion of i n v e s t i g a t i o n al m e d ic i n a l p r odu c t s ; R e s e a r c h I P ha s t h e m e a n i n g g i ven i n C l a u s e 1 9 .3 ; S e r v i c e s ha s t h e m e a n i n g g i v e n t o i t i n C l a u s e 2.5 ; Si t e m ea ns a ny I n s t i t utio n ' s si t e w h e re t h e S t u d y is b e i n g c ond u c t e d ; S t u d y ha s t h e m e a n i n g g i ven t o i t i n t h e R ec i t a l s ; S t u d y D r u g m ea ns CL I E N T ( o r s u c h oth e r ph a r m a c eutic a l s p onsor w h o i s au t ho r i zi ng C L I E N T ) ph a r m ac e u t i ca l f o r m of an ac t i v e i n g r ed i en t or p l acebo or c o m p a ra t or p ro d u c t be i ng t e s te d or u s ed a s a r e f e r e n c e i n a S t u d y a s s e t o u t in a P ro t o c ol ; S t u d y S u p p l i e s ha s t h e m e a n i n g giv e n t o it i n C l au s e 6.2 . 1 ; S u b co nt r a c t o r ha s t h e m e a n i n g g i v e n t o i t i n C l a u s e 2 9 ; T e rr i t o r y ha s t h e m e a n i ng g i v e n t o i t i n t h e C o n tr ac t P a rtic u la r s ; U A E m eans t h e U n ite d Ar a b E m ir a t e s ; U A E C i v il C o d e : m eans F e d e r a l L a w N o. (5 ) o f 1985 on t h e Ci v il T r a n s ac t i o n s L a w of t h e U. A . E . V A T m eans t h e v a l u e - ad d e d t ax a s ap p l i ed i n t h e U A E; a nd W O ha s t h e m e a n i n g g i ven t o it i n C l a u s e 2.2. I n t e r p r e t a t io n 1. An y a m b i g u i t i e s i n t h e t e r m s o f t h i s A g r ee m e n t w i ll no t b e pre s u m p t i v el y c o ns tr ued for or a g a i n s t e i t h e r p a rt y . 2. H e adin g s a r e for conv e ni e nc e o n l y . 3. Th e s ched u l e s and e x h i b it s f o r m p a r t of t h i s A g r ee m en t. A ny r e f e re n c e to t h i s A g r ee m e n t i n cl u de s t h e s che d ul e s , e x h i bi t s a nd e x e c u te d W O s and C O s . 4. A s u s ed i n t h i s Ag re e m e n t i ng i ng w i t h o u t l im i t a t i o n . 5. Un le ss t h e c o n t ex t o t he r w i se r e q ui r e s , w or d s i n t h e s in g u la r s ha l l i nc l u d e t h e p l ur al and i n t h e p l u r a l s h a ll i nc l u d e t h e s i n g u l a r. 6. Un le ss ex p re ss ly p r ov i ded o the r w i s e i n t h i s A g r e e m e n t , a r e f e re n c e t o l e gi s l a t i on o r a leg i s lati v e p r o v i s i on i s a r e f e r e n c e t o i t a s a m e n d e d, e x t e n d e d or r e - enac t e d f ro m time t o t i m e . 25 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

E X E C U T I O N V E R S I O N S C HE D U LE 2 F O R M OF W O R K O R D ER T o be a tt a c h e d i n a s e p a r a t e c o v e r : 26 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

S C H E D U L E 2 F O R M A T O F W O R K O R D ER T h i s W or k O rd e r N o . [ 1] ( W O C omm e r cia l s b e l ow b y a n d b et w ee n : t h e C o m m e n ce m e n t D a t e s e t o u t i n t h e K e y 1 ) [ T O B E CO M PLETE D ] C L I E N T ; a n d 2 ) I N S IGH T S P H A R M A C E U T I C A L R E S E A R C H LL C I R O S , p u r s u a n t t o t h e Ma s t e r S e r v ic e s A g re e m e n t d a t e d Ag r e e m e nt b et w ee n C L I ENT a n d IR O S . T h i s W O s p ec i f i e s t h e s e r v i ce s t o b e p r o v i d e d b y I RO S i n t h e T e rr i t o r y i n c o n n ec t i o n w i th t h e St ud y (t h e S e r v ice s ) a n d t h e d eta i l s f o r the fo ll o w in g : a) P r o t o c o l ( E x h i b i t A ) : b) S c o p e o f W o r k ( E x h i b i t B ) ( ; c) P r o je c t S c h e du l e ( E x h i b i t C ) ; d) P r o je c t B u dg e t ( E x h i b i t D ) ; a nd e) P a y m e n t S c h e d u l e ( E x h i b i t E ); a nd f) Cl i n i ca l T r ia l A gr ee m e n t te m p l at e ( E x h i b i t F ) . T h e P a r t i e s h e r e b y a g re e t h a t I RO S sh a ll p e r f o r m the S e rv i ce s i n t h e T e rr i t o r y a n d C L I E N T s h a l l p a y f o r s u c h S e r v i ce s, a l l i n acc or d a n c e w i t h t h e p r o vis i ons o f t he A gr e e m e n t a n d t h e te r ms o f t h i s WO. 1 . K E Y C O M M E R C I AL S I TE M D E T A I L S C o m m e n ce m e nt D a t e [ D a t e o f l a st s i g n a t u r e o f t h i s W O , p r o v i d e d b o t h P a r tie s s i g n / o r a s p eci f i e d d a t e i f a p p l ic a b l e ] T e r m C omm e n c e m e n t D a te u n t i l s at i s f a c t or y c o m p l e ti o n o f t h e Ser v i ce s , u n le ss t h i s W O i s t e rm i n at e d ea r l i e r i n ac c o r d a n c e w it h t he t e r ms of Ag r ee m e n t . P r o j ec t R e p r e s e n t at i v e M a n a g e r F o r C l i e n t : N a m e : [ In s e r t ] P o s i t i o n : [ In s e r t ] A dd r e ss: [ In s e r t ] T el e p h o n e : [ In s e r t ] E m a i l : [ In s e r t ] F o r I RO S : N a m e : [ I s la m E l T a nt a wy] P o s i t i o n : [ In s e r t ] A dd r e ss: [ In s e r t ] T el e p h o n e : [+ 97 1 5 45 3 5 3 5 5 1 ] E m a i l : [ is l am . e lta n ta wy @Se r vi c e P ro v i d e r . a i ] S p o n s o r [ In s e r t d e t a i l s o f S p o nso r ] S t ud y T i t l e [ i n s e r t ] P r o t o c o l N u m b e r [ i n s e r t ] S t ud y D r u g s [ i n s e r t ] A n y R e q u i r e d E q u i p m e n t [ i n s e r t ] S t ud y A s s u m p t i o n s T h e k e y S t u d y a ss um p t i o n s on w h ic h t h i s W O h a s b ee n a g r ee d a r e a n d i n acc ord a n c e with w h ic h the S e r v ic e s s h al l b e p r ov i d e d a r e : N u m b e r o f S i t e s wi l l b e : [ i n s e r t ] R e c r u i t m e nt R a t e a ss u m p t i o n s : [ i n s e r t ] M i n i m um / M a x i m um T r i a l S u b j ec t s T o B e En r o l l e d : [ i n s e r t ] \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l

2 . D E F I N I T IO N S A N D I N T E R P R E T T IO N 2 . 1 Ca p it a lize d te r ms a r e a s d e f i n e d i n t h e A gr ee m e n t , u n l e ss o t h er wise d e f i n e d i n t hi s W O . T h e fo l l o w i n g w ord s s h a ll h a v e t h e fo ll o w i n g m e a nin g s f o r t h e p u r p o s e s o f this W O : \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l D E T A I L S I TE M ] i n s e rt S i t e M a n a g e me nt A ss u m p t i o ns: [ ] i ns e rt ot h e r c a te go r i e s o f ap p l i c a b l e ass u mpt i o n s [ U A E Terr it o r y I R O S s h a l l p r o v i d e t h e S e r v i ce s i n t h e T er r i to r y i n acc o r d a n c e w i t h t h e S c o p e o f W o r k s e t o u t i n T a b l e 1 : S c o p e o f W o rk i n E x hib i t B . I R O S s h a l l d e l iv e r t h e S e rv ic e s a s p e r t h e a g r ee d ti m eli n e s s e t o u t i n t h e P r o je c t S c h e du l e a tt a c h e d h e r et o a s E x h i b i t C . T h e P a r t ie s ho w e v e r u n d e r s ta n d a n d a gr e e t h a t t h i s t i m el i n e is d e p e nd e n t o n t i m e ly a p p r ov a l o f k e y S t ud y d o c u m e n t s a n d a cti v i t ie s b y t h i r d p a r ti e s , i n c lu d i n g Re gu l a tor y Au t h o r iti e s, I R B a n d I EC a n d m a y n e e d t o b e a u t o m a t ica l l y e x t e n d e d i n a cc o r d a n c e w i t h Cla u se 7 o f t h e A gr e e m e n t or a m e n d e d b y f or m a l C O . S c o pe o f W o r k I R O S ' s ta nd a r d o p e r a t i n g p r o c e du r e s w i l l b e u s e d in p e rf o r m a n c e o f t h e S e r v ic e s t o t h e e x te n t a pp r o p r i at e , unl e s s o t h e r w i se s e t ou t i n t h e c o r r e s po n d i n g P ro t o c o l . A pp lic at i o n o f I R OS' SOPs I R O S, C L I E N T a n d In s t it u ti o n s h a l l e n t e r i n t o a t r i - p a r t it e c l i n i c a l t r i a l a gr ee m e n t ; a n d I R O S ' Cl i n i c a l T r ia l A g r e e m e nt te m p la t e w i l l be u s e d f o r c on t r act in g w it h In s t it u t i o n s. C l i n ic a l Tri a l Ag ree m e n t S h ou l d I R O S b e r e q u e s te d b y C L I E N T t o p e rf o r m a d d i ti o n a l s e rv ice s w h ic h a r e n o t i n cl u d e d in t h e s c o p e o f t h i s W O , t h e se s e rv ice s s h al l b e p r o vid e d by I R O S fo r a n a d d i t i on a l S er vi c e s F e e t o the S e r v i ce s F ee s s e t ou t in t h e P r o j ec t B u d g e t , w hi c h f e e s s h a l l b e m u t u al l y a g r e e d i n w ri ti n g i n a d v a n c e of t h e c o m m e n c e m e nt o f t h e a d d i ti on a l s e rv ice s . C L I E N T s h al l b e r e s p o n s i b l e fo r t h e c o st o f a ll P a s s - T hr ou g h Costs r e lat i n g to t h e s e a d d i ti o n a l s e rv ice s . A dd i t i o n a l S er v ice s s p on s o r o f t h e S t u d y t o r e m u n e r at e a n y In s ti t u t i o n s i n t h e T e rr i t o r y p a r tic ip ati n g i n the S t ud y a n d t h a t t h e CL I E N T w ill b e r e s p o n s ible f o r t h e d ir ec t p a y m e n t t o In s t it u t i o n s o f a n y f ee s, e x p e n s e s o r c o s t s i n c u rre d b y I n s ti t u t i o ns i n r e l ati o n t o t h e S t u d y . P a y m e nt o f f e e s , c o s t s a n d e x p e n s e s i n c u rre d by I n s t i t u t i o ns M e a n i ng D e f i n e d Ter m T h e S e r vi c e F ee s a n d P a s s - T hr ou g h C o s t s p a y a b l e b y C L I E N T to I R O S i n acc ord a n c e w i t h t h e P ro jec t B u d g e t s e t o u t i n E x h i b i t D a n d t h e P a y m e nt S c h e du l e s e t for t h in E xh i b i t E C h a r g e s T h e Ke y C o mm e r c i al s s e t o u t i n S ec t i o n 1 K e y C o mm er ci a l s T h e p a ss - t hro ug h c os t s s e t o u t i n P a r t 3 o f t h e P r o j ec t B u d g e t i n E xh i b i t D a n d s h a l l fo r t h e a v o i d a n c e o f d ou b t i n c l u d e a n y c os t s t h a t a r e n o t d ir ec t c o s t s i n c u r r e d b y I R O S ( su c h a s l a b o r c o s t s) i n t h e p e r f o r m a n c e o f S e rv ice s, i n cl ud i n g w it ho u t l i m it a ti on , c o s t s fo r S e r v i ce - r e l ate d t r a v e l a n d S u b c o n t r ac t o r s f ee s (o t h e r t h a n f or In s t it u t i o n s, w hi c h f ee s a r e p a y a b l e b y C L I E N T t o I n s ti t u t i o n d i r e ct l y ) f o r i t e ms s u c h a s pr i n ti ng , l a b or at o r y f e e s, s h i p p ing a n d f a c s i mi l e c o s t s , la ng u a g e t r a n s la t i o n , t e l e ph o n e c ha r g e s, a d v e r t i s i n g , i n v e s ti g a t o r m ee t i n g e xp e n s e s, a nd / o r o t h e r e xp e n s e s a ss o c i a te d wi th t h e c o n d u c t o f t h e Stu d y . T r a v e l c o s t s i n c lud e , bu t a r e n ot l i m i te d t o, t h o se a ss o cia t e d w i t h r e a s on a ble t r a n s p or tati o n ( E c o no my f a r e s fo r ai r p la n e t r i p s, 2 n d cla ss tr a v e l i n t r ai n s ) , l od g i n g ( 3 s t a r h o te l s m a x i m u m pr o v i d e d s u c h a r e a v a i l a bl e ) a n d m e a l s . P a ss T h r o u g h C o s t s T h e c urr e n c y c onv e r s i o n r a t e ( s) s e t o u t i n t h e P a r t 3 o f t h e P a y m e n t S c h e du l e at t ac h e d a s E x h i b i t E. E x c h a n g e R at e

2. T h e E x h i b i t s t o t h i s W O fo r m a n i nt e g r a l p a r t o f th i s W O a n d a r e h er e b y i n c or po r a t e d b y r e f e r e n c e . 3. S a v e a s s p eci fi e d h e r ei n al l te r ms i n t h e A g r e e m e n t a r e d e e m e d i n c o r por ate d i n t h i s W O a n d s h a l l gov er n t h e p e r f o r m a n c e o f the P a r t i e s ob li g at i ons un d e r t h i s WO . 4. A n y c o n fl ic t b e t wee n t h i s W O a nd t h e A gr ee m e n t s h a ll b e r e s o l v e d in acc ord a n c e w i t h C l a u s e 2 . 2 o f t h e A gr ee m e nt . 5. W i t h r e s p ec t t o t he S e rv ice s p e rf o rm e d un d e r th i s WO, t h i s W O a n d t h e A gr ee m e n t , c o n t a i n t h e e n t i r e a gr ee m e n t of t h e Pa r t i e s i n re s p ec t o f t h e s ub j ec t m a t te r h e r et o . 3. P R O J E C T M A N A G E M E N T 1. C L I E N T h a s a pp o i n t e d t he C L I E N T Pr o je c t Re p r e s e nt ati v e w h o s h al l b e r e s p o n s i b l e fo r t h e c o ord i n ati o n o f al l m att e r s r e l a ting t o t h e S e r v i ce s . I RO S u n d e r ta k e s t o c omply w i t h t h e r ea s o n a b l e i n s t r u c tions o f C L I E N T a n d / o r CL I ENT , w hi c h m a y b e g i v e n f r om t im e t o ti m e i n w ri ti ng . 2. I RO S h a s a p p o i n te d the I RO S P r o je c t Re pr e s e n tat i v e w h o s h a ll b e r e s p o n s i b l e f o r t h e c o o rd i n a t i o n o f al l m at t e r s r e l a ting t o t h e d eli v e r y of S e r v i ce s on b e h al f o f I ROS . 3. T h e C L I E N T P ro j ec t Re p r e s e n t at i v e a n d t h e I RO S P r o jec t Re pr e s e n t ati v e s h a l l me e t a s of te n a s r ea s o n a b l y p r a cti c a b l e t o e n su r e e ff ic i e n t p e r f o rm a n c e o f the S e r v i ce s , [ a n d n o le ss t h a n o n c e in ea c h p e r i o d of t hr e e ( 3 ) m o n t h s und e r t h i s W O ] a t a pl ac e a n d ti m e t o be a g r ee d t o by t h e P r o j ec t Re pr e s e n t ati v e s . T h e se m eeti ng s m a y b e v i r t u al . 4. T h e I RO S P r o je c t Re p r e s e nt ati v e sh a ll: S e r v e a s a p r i m a r y p o i n t of c ommu n i cat i o n a n d r e s o u r c e f o r S tudy o v e r s i g h t f or C L I E NT , o t h e r s e r v i c e p r o v i d e r s a n d t h e S t u d y te a m ; C r eat e a m a n a g e m e n t fr a m e wor k t o op t i m iz e t h e s k il l s a n d p e r form a n c e o f fun cti o n a l le a d s, a n d dr i v i n g f o c u s a n d e x e c u t i o n o n t h e q u al i t y a n d e ffi cie n c y o f ind i v i du a l ta s k s; P r ov i d e pr o a cti v e le a d e r s h i p a nd d ir ect i o n t o t h e S t u d y t e a m, in cl u d i n g c o m p r e h e n s i v e p r o jec t p l a n s fo r mi le s t on e s , q u a li t y a n d bu d g e t a n d m ai n ta i n i n g c l ie n t - s p eci fi c g u i d el i n e s; D ir ec t t h e I R OS g l o b a l r i sk m a n a g e m e n t p r o c e s s, a dd r e s s i n g a n d mi ti g a t i n g po te n t ia l o b s tac l e s, a n d a ss u ri n g t i m el y a n d c os t - e ff ic i e nt pr o j ec t d el i v e r y ; U t il i z e I RO S s y s t e ms a n d p r o ce ss e s t o a ss u r e e ff ic i e n c y a n d a c c u r a c y t h r ough o u t t h e S tud y ; A t te n d r e g u l a r ca l l s w it h C L I E N T to d i s c u ss r ec r u i t m e n t , p ro t o c o l d e v i a ti o n s, s it e p e rf o rm a n ce , q u a l it y a n d ti m e l i n e s; a nd P r e p a r e a nd d e li v e r m o n thly r e p o r t s o n t h e p r og r e s s o f t h e S t u dy . 4. E X E C U T IO N 1. T h i s W O m a y b e e x e c u t e d i n a n y n umb e r o f c ou n t e rp a r t s e a c h o f w h ic h , w h e n e x e c u t e d , s h a l l c o n s t i tu t e a n o r igin a l, bu t a l l t h e c ou n te rp a r t s tog e th e r s h a l l c o n s t it u t e a s i n g l e b inding l e g a l d o c u m e n t . T h i s W O m a y b e e x e c u te d t h ro ug h t he u se o f a n el e ct r on i c s i g n a t u r e . T r a n s mi s s i o n o f t h e e x ec u te d s i gn at ur e p a g e o f a c o un te r p a r t of t h i s W O b y ( a ) f a x o r ( b) e m ai l (i n P D F, JPE G o r o t h e r a g r ee d f o rm a t ) to a n o t h e r P a r t y s h a l l t a ke e f f e c t a s d el i v e r y o f a n e x ec u te d c o un t e r p a r t o f t h i s W O . I f e i t h e r m et h o d of d e li v e r y is a d o p te d , w i t h o u t p r e j u d i c e t o t h e v al i d it y o f t h e W O t h u s m a d e , e a c h P a r t y sh a ll pro v i d e t he o t h e r s w it h t h e o ri g i n a l o f s u c h c ount e r p a r t a s s oo n a s r ea s o n a b l y p o ss i b l e t h e r e a f t e r . N o c o u n te rp a r t s h a ll b e e ff ec t i v e u n t i l eac h P a r t y h a s e x ec u te d a nd d e l i v e r e d a t l e a st o n e c o u n te r p a r t . [ S i g n a t ur e C l a u s e fo l l o w s] \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l T h e p r o t o c o l w i t h t h e p ro to c o l n u m b e r s p e c i f ie d i n t h e K e y C o mm e r cia l s a s a p p r o v e d b y C L I E N T, t h e E t h i c s C o mm i tt e e a n d t h e A b u D h a b i D e p a rt m e n t o f H e alt h , a n d a tt a c h e d a s E xh i b i t A . P r ot o c o l T h e c l i n ica l r e s e a r c h s e r vi ce s to be p r ov i d e d b y I RO S i n r ela t i o n t o t h e S t u d y u n d e r t h i s W O , t h e s c o p e o f w h i c h i s m o r e p a r t i c u l a r l y i d e n ti fi e d i n E x h i b i t B , i n cl ud i n g s er vi c e s w h i c h a r e i n ci d e n ta l o r a n ci l la r y t o s u c h s e r v i ce s . S er v ice s T h e s e r vi c e s f ee s s e t o u t i n P a r t 2 o f t h e P ro jec t Bu d g e t i n E x h i b i t D . S er v ice s F e e

I N W I T N E SS W H E R E O F , d u l y a ut h o r ize d r e p r e s e n t a t i v e s o f t h e P a r t ie s h a v e e x ec u t e d and d eli v e r e d t h i s A g r e e m e n t , i n du p l ic at e . A C K N O W L E D G E D , A C C E P T E D A N D A G R E E D T O: [ T O B E C O M P L ETE D ] I N S IGH T S PH A R M A C E U T I C A L R E S E A R C H LL C B y : B y : N a m e : T i t le : D a te : N a m e : T i t le : D a te : \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l

E X H I B IT A T HE P R O T O C OL \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l

E X H I B IT B S C O PE O F W O R K P A R T 1 : S E R V I C E S I RO S s h a l l pro v i d e t h e Se r vi c e s i n d i c ate d b y m a r k [ X ] i n r ela t i o n t o t h e S t u d y f o r t h e li f ec y cl e ( s ) o f t h e S t u d y s e t o u t in t h e c o l u mn t it l e d ' D u ra tio n ' , o r fo r s u c h oth e r p e r i o d a s m a y b e s p ec if ica l l y s t ate d i n C o l u mn 3 b el o w . T a b l e 1 : S c o p e o f S e r v i ce s \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l S er v ice s A pp lic a b i li t y D u r at i o n U n i t P r i c e N u m b e r o f U n i t s T a s k P r i c e C l i n ic a l w r i t i ng [ i n s e r t ] ] [ i n s e r t ] [ i n s e r t c o st p e r ac t i v it y ] [ P la n n i n g ] [ X ] P r e p a ri n g p at i e n t i nfo r m a ti o n s h e e ts [ P la n n i n g ] P r e p a ri n g i n fo r m e d c o n s e n t f o r ms [ S ta r t - u p ] P r e p a ri n g S tudy p la n s P r e p a ri n g c li n ic a l s t u d y r e p o r ts i ns e rt o t h e r r e la te d [ e r vice s] s R e g u l at o r y Af f ai r s [ P la n n i n g ] P r e p a r a t i o n a n d m a n a g e m e n t o f cl i n i ca l t r ia l a p p l ica t i o n s [ P la n n i n g ] L o ca l E t h i c s C o mm it t e e S u b m i ss i o n a n d A ppr o v a l N a ti on a l In s t it ut i o n a l Re v ie w B o a r d S u b m i ss i o n [ P la n n i n g Cl o s i n g ] P r e p a ri n g a n d m a n a g i n g s u b s ta n t i a l a m e nd m e n t s [ Cl o s i n g ] P r e p a ri n g a n d s u b m i t ti n g e n d o f t ri a l n o t i f ic a ti on s t o Re g u l at or y A ut h or it i e s A nn u a l Re p o r t s t o E C s a n d Re gu la t o r y A ut h or it i e s i ns e rt o t h e r r e la te d [ e r vice s] s P r oj ec t M a n a g e m en t [ O n e ] m eet i n g d u ri n g S t a r t - u p K i c k - of f M ee ting T e r m of t h e A gr ee m e n t Cl i e n t I R O S m ee t i n g s a nd ca l l s [ M on t h l y ] Re p o rt i n g on S t u d y pr o gr e ss [ Rec ru it m e nt ] P r o je c t T ea m T r ai n i n g i ns e rt o t h e r r e la te d [ ] e r vice s s S t udy S i t e M a n ag eme nt and M o n i to ri ng [ S ta r t - u p ] S elec t i o n of S t u d y

\ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l T a s k P r i c e N u m b e r o f U n i t s U n i t P r i c e D u r at i o n A pp lic a b i li t y S er v ice s S ite ( s) Id e n t i f ic a ti o n a n d s ele c ti o n o f P r i n ci p a l In v e s t i g a t o r [ S ta r t - u p ] P r e - S t u d y Vi s i t [ Rec ru it m e nt ] S it e M a n a g e m e n t a n d C o - or d i n a t i o n [ S ta r t - u p ] S it e C o n t r a ct s In v e s t i g a t o r S i te F il e P r e p a r a t i o n [ Rec ru it m e nt ] S it e I ni t i a t ion V i s i t [o n e v i sit d u r i n g Rec ru it m e n t ] S it e M ai n te n a n c e V i s i t [ O n e v i s it dur i n g Cl o s u r e ] S it e Cl o s u r e V i s i t C o - or d i n a t i n g ac t i v it i e s ac r o ss t h e S t u d y S i t e s i ns e rt o t h e r r e la te d [ e r vice s] s C R O M a n a g e m e n t [ Rec ru it m e nt ] CR O - S p on s o r Call s i ns e rt o t h e r r e la te d [ e r vice s] s I n s u r a n c e [ S ta r t - u p ] A rr a ng i n g L o c a l In s ur a n c e Ce r t i f i ca te i ns e rt o t h e r r e la te d [ e r vice s] s R e g u l at o r y C ons ul t i n g i n re s p ec t o f In v e s ti g a t io n al M e d i ci n a l P r o d u c t ( I M P) [ S ta r t - u p Rec ru it m e n t ] Re g u l at or y c o n s u l t a n c y s e r v ice s i n r ela t i o n t o i m por tat i o n of IM P Re g u l at or y c o n s u l t a n c y s e r v ice s i n r el a ti o n t o s t or a g e a n d d el iv e r y o f I M P t o S tudy s i te s i ns e rt o t h e r r e la te d [ e r vice s] s I n fo r m e d C o n s e n t C ol lec t i o n C o llec t w ri tte n c o n s e n t o f eac h s u b je c t p a r t i ci p at i n g i n S t u dy , i n t h e f o r m a u t h o ri ze d b y t h e a p p l ica b l e Re g u l at or y A ut h or it i e s, i n cl ud i n g fo r c o lle c ti o n a n d u se o f s a m p le s a n d u se o f P e r s o n a l D ata . i ns e rt o t h e r r e la te d [ ] e r vice s s R e c o r d s a nd Da t a M a n ag eme n t Ess e n t ia l D o c u m e n ta t i o n C o llec t i o n

[ N o t e t o D r a f t e r : T a b le t o b e u p d a t e d t o i n c l u d e t h e s e r vi ce s t h a t I R O S wi l l b e p r ov i d i n g f o r t h e s p ec i f i c S t ud y . T h e s e r v i c e s n a m e d i n t h e t a b l e a r e n o t e x h a u s t i v e a n d s h o u l d b e a d d e d t o i f o t h e r s e r v i ce s a r e r e q u i r e d fo r a S t u d y . ] P A R T 2 : T R A N S F E R O F O B L IG A T IO N S L I S T T h e P a r t i e s h e r e b y a gr e e a nd ac k n o w l e d g e t h a t t h e C L I E N T t r a n s f e r s t o I RO S, wh o a s s um e s, r e s p ons i b i lity f o r t ho s e ac t i v it i e s s e t o u t i n T a b l e 2 : De l e g a t i o n o f A u t h o r i t y i n r e s p ec t o f wh i c h i t h a s e xp r e ss l y b ee n p r o v i d e d t h a t I RO S i s r e s po n s i b l e . C L I ENT s h a l l r e t a in r e s p o n s i b i l it y f o r al l o t h e r ac t i v it i e s . C L I E N T r e s e rv e s t h e r ight t o a ss u m e a n y o f t h e d u tie s d ele g at e d t o I R OS u nd e r t h i s W O a t a n y t i m e o n w ri tte n n o t ic e t o I RO S, i n w h i c h ca se T a b l e 1 : S c ope o f S e r v i ce s a n d t h i s T a b l e 2 : De l e g a t i o n o f A u t h o r i t y s h a l l b e a m e nd e d ac c o r din g ly . T a b l e 2 : De l e g a t i o n of A u t h o r i t y F o r p u r p o s e s o f t h i s t a b le : \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l T a s k P r i c e N u m b e r o f U n i t s U n i t P r i c e D u r at i o n A pp lic a b i li t y S er v ice s Rec or d S t o r a g e a n d A r c hi v i n g i ns e rt o t h e r r e la te d [ e r vice s] s S a f e t y M a n ag e m en t P r o ce ss i n g o f S e r i ou s A dv e r se E v e nts Re p o rt i n g of s e r i o u s u n e xp ecte d d r u g a d v e r se r eact i o n s ( S U S A R s) t o Re g u l at or y A ut h or it i e s, E th ic s C o mm it t ee s a n d In v e s t i g a t or s [ D e v e l o p s a f et y m o n i t or i n g p l a ns] i ns e rt o t h e r r e la te d [ e r vice s] s Qu a l i t y a nd C o m p l i a n c e T r ia l M a s te r F i l e P r e p a r a t i o n T r ia l M a s te r F i l e M a in te n a n c e Ret ur n o f T r i a l M a s t e r Fi l e Re v ie w o f s t a n d a r d o p e r a t i o n p r o c e d u r e s i ns e rt o t h e r r e la te d [ e r vice s] s R e cr u i t me nt of p a t ie n t s Rec ru it m e n t o f p ati e n t s [P a r tie s t o i ns e rt a ny o t h e r S e r vi ce s t h a t wi l l a pp l y t o t h i s W O ] F o ll ow - up A c t i v it ie s i ns e rt a n y f o l l o w - up [ ] cti v it i e s a

' R ' m ea n s ' Re qu e s te r ' ' A ' m ea n s 'App r ov e r ' ' I ' m ea n s [ i n s e r t ] . [ N ot e t o d r a f t e r: T a ble o f r e s po n s i b i l i t ie s t o be u p d a te d t o s u i t t h e sp ec i f i c S t u d y . T he l i s te d r e s p o n s i b i li ti e s a r e n o t e x h au st i v e . ] P A R T 3 : I R O S PE R S O N N E L I RO S s h al l m a k e use o f the f o l lo wi n g I ROS P e r s o n n e l f or p urp o s e s o f pr o v i d i n g t h e S e r v i c e s: ( A ) : E m p l oy ee s : ( B ) : C o n t r a c t o r s : ( C ) : C o n s u l ta n t s : \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l R e s p o n s i b l e P a r t y I R OS C L I E N T Li f ec y cl e T a s k [I R O S] S t a r t - u p K i c k - of f M eet i n g [I R O S] S t a r t - u p P r o je c t M a n a g e m e nt [I R O S] S t a r t - u p S elec t i o n of S i t e s a nd I nv e s t i g at or s [I R O S] R S t a r t - u p P r e - s t u d y V isi t s [I R O S] R ec r ui t m e nt S it e M a n a g e m e nt a n d c o o r d i n at i o n [I R O S] R ec r ui t m e nt S i t e P a y m e n t P r o c e s s i n g a n d T r a c king [I R O S] R R ec r ui t m e nt T M F M a i n t e n a n c e [I R O S] R C l osu r e S it e Cl o s u r e V i s i t ( S C V ) [I R O S] R C l osu r e A nn u a l Re p o r t t o R A s a n d E C s [ Cl i e n t ] A I S t a r t - u p C R F D e v e l o p m e nt [ Cl i e n t ] I S t a r t - u p D a ta b a se S e t - up a n d V a li d a t i on [ Cl i e n t ] I S t a r t - u p E d i t C h e c k P ro g r a m i n g [ Cli e n t ] I Rec ru it m e n t D a t a Cle a n i n g a n d Q u e r y P r o ce ss i n g ( eCR F) [ Cl i e n t ] I R ec r ui t m e nt E x te rn a l D a t a T r a n s f e r R e c on c i l i ati o n [ Cl i e n t ] I R ec r ui t m e nt C o d i n g [ Cl i e n t ] I A C l osu r e D a ta b a se L o c k [ Cl i e n t ] I S t a r t - u p Ra n d o m iz a ti o n [ Cl i e n t ] I C l osu r e D B T r a n s fe r [ Cl i e n t ] I R ec r ui t m e nt eC R F Li c e n se Li f ec y cl e P o s i t i o n ] i ns er t [ Li f ec y l e D e t a i l s [ i ns er t ] Li f ec y l e D e t a i l s ] [ i ns er t

P A R T 4 : S T U D Y S I T E S [ T h e S t u d y s h al l be ca rri e d o u t a c r o ss th e f o l l o w i n g S t u d y Si t e s: [ i n s e r t ] [ N ot e t o d r a f t e r : T h e a b o v e p r o v i s i o n s h o u l d b e po p u l a te d w i t h t h e p re - s ele c te d S t u d y S ite s if t h e C L I E NT i d e n ti fi e s t h e S t u d y S ite s t o w h i c h t h is W O a pp li e s a n d a c r o s s w h i c h S t u d y S it e s t h e S e r v i c e s s ha l l b e p r o v i d e d .] OR I RO S s h al l id e n t i f y [ i n s e r t nu m b e r ] a p p r op r ia t e s i te s i n the T e rr it or y fo r t h e c o n du c t i n g o f t h e St u d y , eac h s u c h s it e t o m ee t the s p e c i f ic a ti on s pr o v i d e d t o I RO S b y t h e C L I E N T . T h e r e s h o u l d b e [ o n e ( 1 ) ] S t u d y S i t e i n e a c h [ c o u n t r y ] i n t h e T e r r i t o ry , or su c h oth e r num b e r o f S t ud y S ite s a s m a y b e s p eci f i e d b y t h e C L I E N T i n eac h [ c o u n t r y ] i n t h e T e r r i t o r y o r i n eac h s p ec if ie d c ou n t r y i n t h e T e rr i t o r y b y t h e C L I EN T . [ N ot e t o d r a ft e r : t h e a b o v e p r o v i s i o n s h o u l d b e u s e d i f I R O S i s r e q u i r e d t o i d e n t i f y t h e S t u d y S i t e s a s a S e r v i c e u n d e r t h i s W O . ] \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l

E X H I B IT C P R O J E C T S C H E D U L E S T U D Y T IM E L I N E T h e t im el i n e ins e r t e d i n t h i s a t tac hm e n t in d i c ate s t h e a n t i ci p ate d du r at ion o f t h e p r i ma r y S t ud y act i v i ti e s . T h i s t im el i n e i s d e p e n d e n t o n t i m e ly a pp r o v a l o f k e y S t u d y d o c u m e n t s a n d a c tiv i ti e s by C L I E N T a nd ot h e r t h i r d p a r ti e s ( e . g . I R Bs/ I E C s/Si te s) a s n e c e ss a ry . A d just m e nts t o t h i s t im el i ne d u ri n g t h e i n i tia t i o n o f t h e S t u d y ma y h a v e a ca s ca d e e f f ec t o n t h e r e m ai n d e r of t h e ti m eli n e a n d t h e bu dg et . Thus, t h e S t u d y t im el i n e m a y b e a m e n d e d i f r e g u l at o r y a pp r ov a l i s d e l a y e d /e x p e d it e d o r if a n a m e n dm e n t t o the P ro t o c o l r e q u i ri n g I R B / I EC a ppr o v a l is m a d e o r i f r ec ru it m e n t d ela y e d /e x p e d i t e d ; t h e r e v ie w e d ti m e l i n e s sh o u l d b e a gr ee d b y t h e P a r t i e s i n a C O) . \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l M o n t hs D ay s T o F r o m Ph a se P l a n n i ng S t a r t - up R e cr u i t me nt V a cc i n at i o n / F o ll ow - up D ata b a se L o c k C l o s i n g T o t a l

E X H I B IT D P R O J E C T BUD G E T P a r t 1 : C H A R G E S 1. A l l C h a r g e s u n d e r t h i s E x hi b i t a r e to b e i n voi c e d a n d p ai d i n U S D , u s i n g the E x c h a n g e Ra t e . 2. A l l a mo u n t s li s te d h e r ei n a r e e x c l u d i ng V A T o r o t h e r s ale s o r w i t h h o l d i n g ta x e s . I R O S s h a l l b e p ai d t h e V A T i n a dd it io n t o t h e a m ou n t s s e t o u t i n t h i s E x h i b i t (o r a s p r ov i d e d i n T a b l e 1 : S c op e o f S e r v i c e s i n E x h i b i t B , a s a pp li c a b l e ) . 3. T h e t o ta l Ch a r g e s u nd e r t h i s W O ar e ca pp e d a t [ T O B E CO M PLETE D ] . P A R T 2 : S E R V I C E S F EE S S e r v i ce s F ee s will b e b a s e d o n a c t u a l n u mb e r o f S t ud y S ite s, s u b j e ct s r ec ru it e d a n d m a n - mo n ths . T h e S e r v i ce s F ee s s h a l l b e ca l c u l ate d a s t h e s um o f a l l a p p l i ca b l e ta sk pr i ce s s e t o u t i n T a b l e 1 : S c o p e o f S e r v i ce s i n P a r t 1 o f E x h i b i t B [ le ss a n y a gr ee d d i s c o u nt] , w h ic h a m o u nt s h al l b e a s fo l l o w s fo r p u r p o s e s o f t h i s W O : P A R T 2 : P A SS - T H R O U GH C O S T S T h e C L I ENT a gr ee s th a t al l e x p e n s e s i n c u r r e d b y I RO S in r elat io n t o t h e f o ll o w i ng ca t e go r ie s o f p a s s - th ro ug h c o s t s s h a l l b e d e e m e d t o be a p pr o v e d P a s s - T hr o u g h C o s t s fo r w h i c h t h e C L I E N T s h a l l b e l i a b l e du r i ng t h e te rm o f t h i s W O : [ N o t e to d r a ft e r : T a b l e d o e s n ot s e t o u t a n e x ha u s t i v e li st o f p a s s - t hr o u g h c o s t s . T h e se w i l l n ee d t o b e u p d a t e d o n a S t u d y - b y - S t u d y b a s i s . ] [ T h e i t e m pr ic e f o r eac h o f t h e c a te go r i e s o f P a ss - T hr o ugh C o s ts s e t o u t i n the t a b l e a bov e sh a l l b e a u t om a t ica l l y i n c r ea s e d i n l in e w it h a n y i n c r e a s e s i n t h e e xp e n s e s i n c ur r e d b y I RO S f or ca r r y i n g o u t a n y s u c h ta sk d ur i n g t h e te rm o f t h e W O , w i th e ff ec t fr om t h e d at e s u c h t a sk pr ic e h a s b ee n i n c r ea s e d . ] P a s s - T hr o ug h C o s t s w i l l b e p ai d b y t h e C L I E N T . \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l ] i n s e r t [ S u m of a l l T a s k P r i ce s ( U S D ) ] i n s e r t [ D i s c o unt ( i f a p p l i c a b le ) ] i n s e r t [ T o t a l S e r vi c e s F e e (af t e r d i s c o u n t i f a p p li c a b le ) I t e m Ex pe nse ( U S D ) N u m b e r o f U n i t s U n i t P r i c e ( U S D ) E x p e nse I t e m E t h i c s Co m m i tt ee s a nd R e g u l at o r y F e e s F i x e d M o n t h l y Ph o n e C o s t s S t udy I n s ur a n c e C o u rie r , P r i n t i ng & O t h e r S i t e V i s i t E x p e ns e s L a b o r at o r y f ee s L a n g u ag e t r an s la t i o n c o s t s A d v er t i s i ng c o s t s I n v e s t i g a to r m ee t i ng e x p e n s e s Tr a v e l c o s t s H o s p i ta l i t y T o t a l C o ul d w i th h o ld i ng t a x e s C o mm en t : C o mm e n t e d [ 1 ] : a p p l y in a n y c i r c u m s t a nce s i n r e l a ti o n to t h e Ch ar g es ?

E X H I B IT E P A Y M E N T S C H E D U LE 1 . P A Y M E N T S C H E D U L E [I n r e s p ec t of eac h m on t h u nd e r t h i s W O ( w i t h e ff ec t fr o m t h e E ff ec t i v e D a t e ) , I R OS w i l l i nv o i c e C L I E N T fo r t h e S e r v i c e F ee s a n d P a s s - Th r o u g h C o s t s i n c u r r e d b y t he C L I E NT i n t h a t m o n t h . C L I E N T s h a ll p a y eac h i nv o i c e wi t h i n t h ir t y ( 3 0 ) d a y s o f t h e d a t e o f r ecei p t o f s u c h i n vo ice . O R : T h e P a r t i e s h a v e a g r ee d t h a t t h e S e r v ic e F ee s s h al l b e p a i d b y C L I E N T t o I R OS i n [ i n s e r t n umb e r ] i n s ta lm e n t s, eac h f o r t h e a m o u n t s s e t o u t b e low ( " S e r v ic e F e e I n s t a l m e n t s " ) . T h e fir s t S e rv ic e F e e In s t al m e n t s h a l l be p ai d t o I R O S i n a d v a n c e ( a n d a s a d o w n p a y m e n t f o r t h e S e r v i ce s) i n t h e a m o un t s e t o u t i n the ta b l e b e l o w . In s t all m e n t s s h al l o t h e rw i se b e p a y a ble i n r e s p e c t of c om p l et i o n a p p li c a b l e m il e s t o n e o n t h e t e r ms s e t out i n t h e t a b l e b e l o w . I n r e s p e c t o f ea c h s ub s e qu e n t S e rv ic e F e e In s tal m e n t , I R O S s h a l l b e e n t i tl e d to i n v o ic e C L I ENT fo r t h e r ele v a n t S e r vi c e F e e In s t al m e n t o n o r a f t e r t h e a sso c ia t e d m i l e s to n e a s d e f i n e d in t h e t a b l e b e l ow h a s b ee n ac h ie v e d . T o g e t h e r w it h t h e S e rv ic e F e e I n s t al m e n t, I R O S s h al l in v o ic e C L I E N T f o r al l P a ss - T hr o ug h C o s t s i n c urr e d d ur i n g t h a t p e r i o d [ a nd a s s e t out i n t h e t a b l e b el o w] . C L I E N T sh a ll p a y e a c h i n v o ic e w it h i n thi r t y ( 3 0 ) d a y s o f t he d a t e o f r e c ei p t o f s u c h i n v o i ce . M i le s t o n e C o s t T e r m s E x ec u ti o n of t h e W O D ow n P a ym e nt S e r v i c e f ee s: [ i n s e r t ] U SD P a s s - T hr o ug h C o s t s : [ In s e r t ] U SD T o t a l : [ I n s e r t ] U SD [ S t u d y A p p r o v a l & Si te I n i ti a ti on ] S e r v i c e f ee s: [ i n s e r t ] U SD P a s s - T hr o ug h C o s t s : [ In s e r t ] U SD T o t a l : [ I n s e r t ] U SD A ft e r 3 0 d a y s o f i nv o ic e s u bm i ss i o n [ i n s e r t ] S e r v i c e f ee s: [ i n s e r t ] U SD P a s s - T hr o ug h C o s t s : [ In s e r t ] U SD T o t a l : [ I n s e r t ] U SD A ft e r 3 0 d a y s o f i nv o ic e s u bm i ss i o n [ i n s e r t ] S e r v i c e f ee s: [ i n s e r t ] U SD P a s s - T hr o ug h C o s t s : [ In s e r t ] U SD T o t a l : [ I n s e r t ] U SD P A R T 2 : A D V A N C E D P A Y ME N T A n y p o r t ion o f a ny a dv a n c e p a ym e nt m a d e un d e r t h i s W O s h al l b e r e f u nd a b l e t o t h e C L I E N T t o t h e e x te n t t h e a mo u n t o f t h e a d v a n ce d p a y m e n t i s gr eate r t h a n t h e act u a l C h a rg e s d u e b y t h e C L I E N T f o r t h e Se r vi c e s c o mpl e t e d d u ri n g t h e p er i o d t o w h ic h t h e a d v a n c e p a y m e n t r e l ate s, p r o v id e d t h a t I R O S s h al l on l y b e r e qu i r e d to re i m b u r se t h e C L I E N T fo r t h e d i f f e r e n c e b e tw ee n t h e a m ou n t p ai d a s a n a d v a n c e p a y m e n t a nd t h e act u a l C h a r g e s d u e un d e r t h i s W O fo r t h e S e r v ic e s t o wh ic h the a dv a n c e p a y m e n t r ela t e s , o r t h e p e r iod t o w h i c h t h e a d v a n c e p a y m e nt r el a te s . A ft e r 3 0 d a y s o f i nv o ic e s u bm i ss i o n \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l

P A R T 3 : I N V OI C I N G 1 . I nvoi ce s a r e s u b j e c t t o t h e r e v ie w o f P r o j ec t Re pr e s e n t at i v e s a n d I RO S sh a ll pr o v i d e t h e n e ce ss a r y s u pp o rt i n g d o c um e n t s o r j usti f i ca tion i f r e qu e s t e d . 2 . I n vo ice s s h a l l b e a d d r e ss e d t o : p a y m e n t s@ g 4 2 . a i 3. E a c h i n v o i c e mu s t i n c l u d e t h e f o l l o w i n g m i n i m u m d e t a il s : - t h e fu l l b u s i n e s s n a m e a n d a dd r e s s of I RO S i n cl ud i n g t h e t a x / V AT re g i st r a t i o n n umb e r o f I RO S ( if a p p l ica b le ) ; - t h e ti m e p e r i o d t o w hi c h t h e i nv o i c e r ela t e s a n d t h e l o cati o n o f t h e s u p p l y ( i f a p p l ica b l e fo r t a x p u r p o s e s ) ; a nd - I RO S ' b a n k a nd acc o u n t d et a il s fo r p a y m e n t . P A R T 4 : E X C H A N GE R A TE 1 . F o r p u r p o s e s o f d et e r m ining a l l a m o u n t s to b e i n vo i ce d u n d e r t h i s WO, I R O S sh a ll m a k e u se of t h e [ i n s e r t / U S D ] e x c h a ng e r a t e d e t e rm i n e d by [ i n s e r t i n s t i t u ti o n / i n d e x] . I R O S s h a l l a pp l y t h e a pp lica b l e c urr e n c y c o n v e r s i o n r at e a s d e t e r m in e d b y [ i n s e r t i nst i t u tion / in d e x ] o n the d at e o f i n v o ic i n g . \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l

E X H I B IT F C L I N I C A L T R I A L A G R EE M E N T T E M P L A T E \ \ 10 9 0 82 9 4147 - 2 5 7 7 - 1078 v 2 H o g a n L o v e l l s C o n f i d e n t i a l

E X E C U T I O N V E R S I O N S C HE D U LE 3 F D A R EQ U I R E M E N T S U n i t e d St a te s F o od an d D rug A d m i ni s t r a t ion Re g ul a t i ons f or C l ini c a l T r ials (Ti t le 2 1 CF R P a r t s 5 0 a n d 5 6 ) : T o b e a tt a c h ed i n a s ep a r a t e c o v e r : 2 7 R e s t r i c t e d I R OS / M SA / 0 01 0 7 0 / 25 1 0 0 3 Ho gan Love l l s K G G

Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 21CFR5 0 (enhanced display ) page1 of 1 7 2 1 CFR Part 5 0 (Sept. 2 5 , 202 5 ) Th i s content is from the eCFR and i s authori tat i ve but u nofficia l . Title 2 1 - Food and Drugs Chapter I - F o od and Drug Admini s tration, Department of Health and Human Serv i c es S ubchapter A - General Part 5 0 .P. r ! . ! . --- .f.. . . !:: ! . . - . Q . . - J !i ! . s ubpart A - - r . ! . .P.rQY . ! . J g . - † 5 0 . 1 . † . <:?. . P. . : . † 5 0 . 3 P . . - . ! ! . . - . : . S ubpart B . ! . . f . Q . - . . g . Q . . :: ? . ! . . f . . . . - - . Q .. - J <:?.. ! . . † 5 0 . 20 - - - E . ! . E 9 . . ! r - ! . f r . ! . f9 . E . Q .. . - - ! . : . † 5 0 . 22 - £ P ! . . ! 2 n . fr . 2 . . ! . Q . f . 2 . r . . - . £2. Q . . n ! . . r . . 9 . . ! .r . . . Q ! . . f 2 r . . . . ! . Q . ! . . ! . . r i . . --- . ! . ! . . ! . £ . ! .. ! QY . . ! . . ! 9 . . ! . ! . 2 n . : . † 5 0 . 23 - 9 . P ! . ! . Q . . f . 2 . .. . 9 . . - r . ! . . . r . . 9 . . ! E . . . Q ! . . : . † 5 0 . 24 - 9 . P ! . . ! 2 . . fr . Q . . . ! . f . 9 . . . . . Q .. 9 . . . - - . .. . . 9 . . ! E . - ! . . . . f9 . r .. - r. 9 . Q'?.Y. . . . E . . : . † 5 0 . 25 . ! . . ! . 9 . . f . . ! . . f . 9 . r . . .. - - . Q . : . † 5 0 . 27 P . !:? . . - - ! ! ! . Q . . . . Q f .. ! f2 . . . - . . !?.2 . . - - . . : . Subpart C [Reserved] s ubpart D A . . . ! ! . 2 . . . ! . f . 9 . r . . . f r . . G . . ! . ! r . ...! . . . g . ! . ! . . ! . . ! . . ! .Y . . . . . ! . 9 . ! ! . Q . . † 5 0 . 5 0 . ! . R . -- - ! . . ! . . . : . † 5 0 . 5 1 _ g _ ! . ! . . ! . £ . ! J Y . . ! . . ! 9 . . ! . ! .!:? . . . · -- - ! . .. ! .Y . . ! .Y . . ! . Q 9 . . 9 r . ! . r . . ! . . -- · - ! . .! . . !... r ! . . : . † 5 0 . 52 _ g _ ! . ! . .!. £ ! . J Y . . ! . . ! 9 . . ! . ! .9 . . . . . ! . QY . Q . !Y . ! . . 9 . 9 . r . ! . - - ! . Q . . .! . . ! . . . ! . . r ! . - - · - ! . .P.r - - . ! . . 9 . . ! . - - Pr P ! 9 . . f... . ! . r . ! . - - f l . .Q..!. . .!.Y ! . . - . ! . . . - 1 £ ! . . : . † 5 0 . 5 3 . g . ! . ! . . ! . 9 . . ! J .Y . . ! . . ! 9 . . ! . ! . !:? . . . . . . ! . QY . Q . !Y . ! . 9 . . . 9 . . ! . -- . - . . . . ! . Q! . ! . .. ! . .. - . --- . Q . . P . 2 . P . . 9 . . 2 . ! . . Q . ! . . - - . - . . 9 . . . ! . Q . ! .Y . . ! . . . ! . . . . - j · - ! . . ! . . . . . . .. ! . ! . . ! .Y . . ! . Y . ! . ! . . 9 . . - . !.!. . ! . . - r:?..'!!. . ! . . 9 . . .. . - . . . . - - j ' . . .. - 2 . - . 9 !. . . £ 2 . . Q . ! ! . 2 Q . . . † 5 0 . 54 _ g _ ! . ! . Q . ! . 9 . . ! . . ! . .Y . . . ! . . ! 9 . ! . ! . Q . . --- - ! . . . . . ! . . . .P.P . ? Y . . . . ! . . . ! . . .P.r - - . . -- .P. P . !:? . . ! . . ! Y .. 2. - - - ! . . ! . - - - P. Y . . ! . ! . . 2 . . . . ! . ! . . Y ! . ! . . . . r 2 . . . P r . . ! . --- - f . f . ! . ! . Q . 9 . .. . h .. b . - ! . . 2 r . . - ! f r . .Qf chi l dre n . † 5 0 . 5 5 . .9 . . ! . . ! . . . . f . ? r . . P . r . ! . . . i . 2 . . . Y . . . P. . ! . . E . . 9 . . . - . ! . . Q . . . Q . . f . . .. . - ! . . Y . ... . ! E . . : . † 5 0 . 5 6 Wards. P ART S O - PR O TE C TION OF HUMAN SU B JE C T S Authority: . . } ... . : : . 9 . : .. ?. J . .. .. . - . - . . . Q . . . Q ? . ?.?.. - . . . . † . • . . 9 . .. - Q . . Qf, . . Q . . . . Q j _. ?. J . .. ? . - J . . : ? . . . : : . 9 . : . ? . 1 . .. ? . J . ? . ? . · S o urc e : - . E . . . 9 . .. May 3 0 , 198 0 , un l ess otherw i se noted.

pa g e2 of t7 21CFR5 0 . 3 (b)( 7 ) ( enha n ced display) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR SD.1 S ubpart A - General Provi s ions † 5 0 . 1 Scop e . ( a ) Th i s part applies to all c l i n i cal i nvest i gat i ons regu l ated by the Food and Drug Adm in i strat i on under sect i ons 505 ( i ) and 520( g ) of the Federal Foo d , Drug, and Cosmet i c Ac t , as well as clin i cal i nvest i gat i ons that support app l i cat i ons for research or market i ng perm i ts for products regu l ated by the Food and Drug Adm in i strat i o n , i nc l ud i ng foods, i nclud i ng d ietary supp l ements, that bear a nutr ient content c l a i m or a hea l th c l a i m , i nfant formu l as, food and co lor add i t i ves, drugs for hu man us e , med i cal dev i ces for human use, b i o l og i cal products for human us e , and e l ectron i c product s . Add i t i onal specific ob l i gat i ons and comm i tments of, and standards of conduct fo r , persons who sponsor or mon i tor cl i n i cal i nvest i gat i ons i nvolv i ng part i cu l ar test art i c l es may a l so be found i n other parts ( e . g . , parts 312 and 812) . Compliance w i th these parts is i ntended to protect the r i ghts and safety of subjects i nvo l ved i n i nvest i gat i ons fi l ed w i th the Food and Drug Adm i nistrat i on pursuant to sect i ons 403 , 406, 409, 4 1 2 , 41 3 , 50 2 , 50 3 , 50 5 , 51 0 , 5 13 - 51 6 , 518 - 52 0 , 7 2 1 , and 801 of the Federal Foo d , Dru g , and Cosmet i c Act and sect i ons 3 5 1 and 354 - 360 F of the Pub l i c Hea l th Serv i ce Act. ( b ) References i n this part to regu l atory sect i ons of the Code of Federal Regu l at ions are to chapter I of t i t l e 2 1 , un l ess otherwise note d . ( 1 . . . E . l . ! : . . ? . . ? . ! ! t May 30, 1980; . F . ! t Jan. 27, 198 1 , as amended at . . ? . . E . ?. . . . !.t May 13, 1998 ; . . 1 . . E . . ! Jan. 1999; . . . . F.. ? Q . !.t Apr. 2 4 , 2001] † 5 0 . 3 D e finition s . As used i n th i s part: (a) Act means the Federal Food, Dru g , and Cosmet ic Act, as amended ( secs. 201 - 90 2 , 52 Stat. 1040 et se q . as amended ( ? . . 1 . .. . : . : . : .. .1 . : . ? . )). (b) Application for research or marketing permit i nc l udes: (1) A co l or add i tive pet i t i o n , descr i bed i n part 7 1 . (2) A food add i t i ve pet i t i o n , descr i bed i n parts 1 7 1 and 57 1. (3) Data and i nformat i on about a substance subm i tted as part of the procedures for establish i ng that the substa n ce is generally recognized as safe for use that resu l ts or may reasonably be expected to resu l t, d i rect l y or i nd i rect ly , in i ts becom i ng a component or otherw i se affect i ng the character i st i cs of any foo d , descr i bed i n . † . † . . J . . ? . Q : 9 . . and . ?.9 . : . .Q. (4) Data and i nformat i on about a food add i t i ve s u b m i tted as part of the procedures for food add i tives perm i tted to be used on an i nter i m bas i s pend i ng add i t i onal stud y , descr i bed i n . † J . 9 . : J . : (5) Data and i nformat i on about a substance subm i tted as part of the procedures for establish i ng a to l erance for unavo i dab l e contam i nants i n food and food - packagi ng mater i a l s , descr i bed i n sect i on 406 of the act. (6) An i nvest i gat i onal new drug applicat i o n , descr i bed i n P. . . J . ? . . . 2 . . ! . . . £ . . l?. ! . f . · ( 7 ) A new drug applicat i o n , descr i bed i n part 31 4 .

2 1 CF R S 0 . 3 (b)(2s) (enhanced dis p l ay) pa g e3 of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S0 . 3 (b)( 8 ) (8) Data and i nformat i on about the b i oavailabil i ty or b i oequ i val ence of drugs for hu man use s u b m i tted as part of the procedures for i ssu i ng, amend i n g , or repea l i ng a b i oequ i va l e n ce requ ir e ment, descr i bed i n part 32 0 . (9) Data and i nformat i on about an over - the - counter drug for human use subm i tted as part of the procedures for c l ass i fyi ng these drugs as generally recognized as safe and effect i ve and not m i sbrande d , descr i bed i n part 330 . ( 1 O ) Data and i nformat i on about a prescri pt i on drug for human use subm i tted as part of the procedures for c l ass i fy i n g these drugs as generally recogn i zed as safe and effective and not m i sbrande d , descr i bed i n this chapter. (11) [Reserved] (12) An app l i cat i on for a b i o l og i cs l icens e , descr i bed i n p . . Q . } .. . ! . . . i . . . . .P . ! . - (13) Data and i nformat i on about a b i o l og i cal product subm i tted as part of the procedures for determ i n i ng that licensed b i o l og i cal products are safe and effect i ve and not m i sbranded, descr i bed i n part 601. (14) Data and i nformat i on about an i n v i tro d i agnost i c product subm i tted as part of the procedures for establish i n g , amend i n g , or repealing a standard for these product s , descr i bed i n part 809. (15) An Application for an lnvestigational Device Exemptio n , descr i bed i n part 81 2 . (16) Data and i nformat i on about a med i cal dev i ce subm i tted as part of the procedures for class i fying these dev i ces, descr i bed i n sect i on 513. (17) Data and i nformat i on about a med i cal dev i ce subm i tted as part of the procedures for establish i n g , amend i n g , or repealing a standard for these dev i ce s , descr i bed i n sect i on 514. (18) An app l i cat i on for premarket approval of a med i cal dev i c e , descr i bed i n sect i on 5 15. (19) A prod u ct devel opment protocol for a med i cal dev i c e , descr i bed i n sect i on 5 15. (20) Data and i nformat i on about an e lectron i c product subm i tted as part of the procedures for establish i n g , amend i n g , or repealing a standard for these product s , descr i bed i n sect i on 358 of the Pub l i c Hea l th Serv i ce Act. (21) Data and i nformat i on about an e lectron i c product subm i tted as part of the procedures for obta i n i ng a var i ance from any e l ectron i c product performance standar d , as descr i bed i n † . . . . . Q . . 9 : . · (22) Data and i nformat i on about an e lectron i c product subm i tted as part of the procedures for grant i n g , amend i n g , or extend i ng an exempt i on from a rad i at i on safety performance standar d , as descr i bed i n . † .J . 9 . . 1 . 9 . : . † . · (23) Data and i nformat i on about a cl i n i cal study of an i nfant formu l a when subm i tted as part of an i nfant for m u l a not i ficat i on under sect i on 4 12(c) of the Federal Foo d , Drug, and Cosmet i c Act. (24) Data and i nformat i on submitted i n a pet i t i on for a n utr i ent content cla i m , descr i bed i n . † . J . 9 . 1 . . † . . . f. ! . . ! .. . 9. P . ! E · or for a hea l th c l a i m , descr i bed i n † .. . } . 9 . 1 . : .?.. 9 . f. . . ! . . 9 . . .P . ! . - (25) Data and i nformat i on from i nvest i gat i ons i nvolv i ng ch il dren subm i tted i n a new d ietary i ngred i ent notif i cat i on, descr i bed i n . † . . . Q : . † . f. . ! . ! . . . P . ! . -

21CFR5 0 . 3 ( m ) (enhanced disp l a y ) pa g e4of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR 5o.3( c ) (c) Cli n ical in v estigation means any experiment that i nvo l ves a test art i c l e and one or more human subjects and that e i ther i s subject to req u i rements for pr i or subm i ss ion to the Food and Drug Adm i nistrat i on under sect i on SOS ( i ) or 520 ( g ) of the act, or i s not subject to requi rements for pr i or submiss i on to the Food and Drug Adm i n i strat i on under these sect i ons of the act, but the resu l ts of whi ch are i ntended to be subm i tted l ater to, or he l d for i nspect i on b y , the F ood and Drug Adm i n i strat i on as part of an app l i cat i on for a research or market i ng perm i t. The term does not i ncl ude exper i ments that are subject to the provis ions of P . . r . . . ? . . . ? .f. . . ! . S . P . . E · regardi ng noncli n i cal laboratory stud i es. (d) Investigator means an i nd i v i dual who actual l y conducts a c l i n i cal i nvest i gat i o n , i.e . , under whose i mmed i ate d i rect ion the test art i c l e is adm i nistered or dispensed t o , or used i nvo l v i n g , a subject , o r , i n the event of an i nvest i gat i on conducted by a team of i nd i v i dua l s, i s the respons i b l e l eader of that team. (e) Sponsor means a person who i n i t i ates a c l i n i cal i nvesti gat i o n , but who does not actually conduct the i nvest i gat i o n , i . e . , the test art i c l e is adm i nistered or dispensed to or used i nvo l v i n g , a subject under the i mmed i ate d i rect ion of another i nd i v i dual. A person other than an i nd i v i dual ( e . g . , corporat i on or agency) that uses one or more of i ts own emp l oyees to conduct a clin i cal i nvest i gat i on i t has i n i t i ated i s consi dered to be a sponsor (not a sponsor - i nvest i gator ) , and the emp loyees are cons i dered to be i nvest i gators. (f) Sponsor - investigator means an i nd i v i dual who both i n i t i ates and actually conduct s , a l one or w i th others, a clin i cal i nvest i gat i o n , i.e . , under whose i mmed i ate d i rect i on the test art i c l e i s adm i nistered or dispensed t o , or used i nvo l v i n g , a subject. The term does not i nc l ude any person other than an i nd i v i dua l , e . g . , corporat i on or agency. (g) Human subject means an i nd i v i dual who i s or becomes a part i c i pant i n researc h , e i ther as a rec i p i ent of the test art i c l e or as a control. A subject may be e i ther a hea l thy human or a pat i ent. (h) Institution means any pub l i c or pr i vate ent i ty or agency ( incl ud i ng Federa l , Stat e , and other agencie s ) . The word facility as used i n sect i on 520 ( g ) of the act i s deemed to be synonymous w i th the term institution for purposes of this part . (i) Institutional review board ( IRB ) means any boar d , comm i tte e , or other group formal l y des i gnated by an i nst i tut i on to rev i ew b i omed i cal research i nvo l v i ng humans as subject s , to approve the i n i t i at i on of and conduct per i od i c rev i ew of such research. The term has the same mean i ng as the phrase institutional review committee as used i n sect i on 5 2 0( g ) of the act. 0) T e st a nicle means any drug ( i nclud i ng a b i o l og i cal product for human use ) , med i cal dev i ce for human us e , human food add i t i v e , co l or add i t i v e , e l ectron i c product, or any other art i c l e subject to regu l at i on under the act or under sect i ons 351 and 354 - 360F of the P u b l i c Hea l th Serv i ce Act ( ? . . . Y . . : . : . : . . ? . ? . an d . ?. . ?.:::? . . !: )) . (k) Minimal risk means that the probabil i ty and magn i tude of harm or d i scomfort ant i c i pated i n the research are not greater i n and of themse l ves than those ord i narily encountered i n da i l y life or during the performance of routi ne phys i cal or psycho l og i cal exam i nations or tests. (I) Legally authorized representative means an i nd i v i dual or jud i c i al or other body authorized under applicab l e l aw to consent on beha l f of a prospect i ve subject to the subject's part i cpat i on i n the procedure(s) i nvolved i n the research. ( m ) F amily memb e r means any one of the follow i ng l egally competent persons: Spous e ; parents; children ( incl ud i ng adopted childre n ) ; brother s , s i ster s , and spouses of brothers and s i sters; and any i nd i v i dual re l ated by b l ood or affi n i ty whose c l ose assoc i at i on w i th the subject i s the equ i va l ent of a fam i l y re l at i onsh i p.

2 1 CF R s o . 22{ b ) (enhanced display ) page5of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0 . 3 (n) (n) Assent means a ch i ld ' s affirmative agreement to partic i pate i n a clin i cal i nvest i gat i o n . Mere fai l ur e to object shou l d no t , absent affirmat i ve agreement, be construed as assent. (o) Children means persons who have not atta i ned the l egal age for consent to treatments or procedures i nvolved i n c l i n i cal i nvest i gation s , under the app l i cab l e l aw of the jurisd i ct i on i n wh i ch the c l i n i cal i nvest i gat i on will be con d u cted. (p) Parent means a c h i l d's b i o l og i cal or adopt i ve parent. (q) Ward means a ch il d who i s p l aced i n the l egal custody of the State or other agenc y , i nst i tut i o n , or ent i t y , consistent w i th applicab l e Federa l , Stat e , or l ocal l a w . (r) Permission means the agreement of parent ( s ) or g uard i an to the part i c i pat i on of the i r child or ward in a clin i cal i nvest i gat i o n . (s) Guardian means an i nd i v i d ual who is author i zed under app l i cab l e State or l ocal l aw to consent on beha l f of a ch i l d to general med i cal car e . f '! . ? . . E. .. . ! ! t May 3 0 , 198 0 , as amended at 1 . E . ! ! . ? . ! ! t Jan. 27, 1981 ; . ?. . 1 : . . E . . Q ! ! t Mar. 3 , 7 9 8 9 ; . ?. . .. E . ? . . Q ? . . t June 18, 1991; . ! . E . 1 3 . . ? . . ? . ? . . . ? . ! ! t Oct. 2 , 1996 ; . . ? . . E . ! ! t July 2 3 , 199 7 · , . . E. . . t Jan. 5 , 1999 ; . . E. . ?.. ! ! t Oct. 2 0 , 1999 ; . . . E. . ? . 9 . ? . . . . !t Apr. 2 4 , 2001; ? . . E . t:! . . . T? . . ? . ! ! t Feb. 2 6 , 2013] S ubpart B - Informed Con s ent of Human S ubjects S o urc e : . X . . . ?.J . .. Jan. 2 7 , 198 1 , u n l ess otherw i se noted. † 5 0 . 20 General requirements for informed c on s ent. Except as prov i ded i n † . † . . . ? . . 9 . . : ? . ? . • . ?. Q : . ?. . and . ?. 9 : . ?. . no i nvest i gator may i nvo l ve a human be i ng as a subject i n research covered by these regu l ations un l ess the i nvest i gator has obta i ned the l egal l y effective i nformed consent of the subject or the subject's l egally author i zed representat i ve. An i nvest i gator shall seek such consent on l y under c i rcumstances that prov i de the prospect i ve subject or the representat i ve suffic i ent opportun i ty to consi der whether or not to part i c i pate and that m i n i m i ze the possi bility of coerc i on or undue i nfluenc e . The i nformat i on that is g i ven to the subject or the representat i ve shall be i n l anguage understandab l e to the subject or the representat i ve. No i nformed consent, whether oral or wr i tte n , may i nc l ude any excu l patory l anguage through wh i ch the subject or the representat i ve i s made to waive or appear to wa i ve any of the subject ' s l egal r i ght s , or re l eases or appears to re l ease the i nvest i gato r , the sponso r , the i nst i tuti o n , or i ts agents from liability for negligenc e . f . . . E. . ?. . ?.t Jan. 2 7 , 198 1 , as amended at . . ..E. ..!.9 . . ? t . Mar. 8 , 1999; . .E. . ? . ?. ! ! t Dec. 27, 2023] † 5 0 . 22 E x c eption from informed c on s ent requirements for minimal risk clin i ca l investi g ation s . The I RB respons i b l e for the rev i e w , approva l , and continu i ng rev i ew of the clin ical i nvestigati on descr i bed i n this sect i on may approve an i nformed consent procedure that does not i nc l ude or that a l ters some or all of the e l ements of i nformed consent set forth i n . † . . ?. 9 : . ? . . ? . ( . ). and. ( ) .. or may wa i ve the requ i rement to obta i n i nformed consent, prov ided the I RB finds and documents the follow i ng: ( a ) The c l i n i cal i nvest i gat i on i nvo l ves no more than m i n i mal risk to the subjects; { b ) The c l i n i cal i nvest i gat i on cou l d not pract i cab l y be carr i ed out w i thout the requested wai ver or a l terat i on;

page 6of 1 7 21CFR5 0 . 2 3 (d) ( 1 ) ( enhan c ed display) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 21CFR5 0 . 22( c ) (c) I f the clin i cal i nvest i gat i on i nvolves us i ng i dent i fiab l e pr i vate i nformat i on or i dentifiab l e b i ospec i mens, the c l i n i cal i nvest i gat i on cou l d not pract i cab l y be carr i ed out w i thout us i ng such i nformat i on or b i ospec i mens i n an i dent i fiab l e format ; (d) The wa i ver or a l terat i on will not adverse ly affect the r i ghts and welfare of the subject s ; and (e) Whenever appropr i at e , the subjects or l egally authorized representati ves will be prov i ded w i th add i t i onal pert i nent i nformat i on after part i c i pat i on. ( l?. . . . E . l . ! : .. ?. . 1 . ! ! t Dec. 21 , 2023} † 5 0. 2 3 Exception from g eneral requirement s . (a) The obta i n i ng of i nformed consent shall be deemed feas i b l e un l ess, before use of the test art i c l e ( except as provi ded i n P . r . 9 . ! . P . . ( ). of th i s sect i o n ) , both the i nvest i gator and a phys i c i an who i s not otherwi se part i c i pat i ng i n the c l i n i cal i nvest i gati on certify i n writ i ng all of the follow i ng: (1) The human subject i s confronted by a life - threaten i ng s i tuat i on necess i tat i n g the use of the test art i c l e. (2) I nformed consent cannot be obta i ned from the subject because of an i nability to commun icate w i t h , or obta i n l egally effect i ve consent fro m , the subject. (3) T i me i s not suffic i ent to obta i n consent from the subject ' s l egal representat i ve. (4) There i s avai l ab l e no a l ternat i ve method of approved or general l y recogn i zed therapy that prov i des an equal or greater l i ke l i hood of sav i ng the life of the subject. (b) I f i mmed i ate use of the test artic l e i s, i n the i nvest i gator ' s opi n i o n , requ i red to preserve the l ife of the subject, and t i me i s not suffic i ent to obta i n the i ndependent determ i nation requ i red i n P . ! 9 ! .P . . . ( ). of th i s sect i on i n a d vance of us i ng the test art i c l e , the determ i nat i ons of the c l i n i cal i nvest i gator shall be made and, with i n 5 work i ng days after the use of the art i c l e , be rev i ewed and eval uated i n wr i t i ng by a phys i cian who i s not part i c i pat ing i n the c l i n i cal i nvest i gat i on. (c) The documentat i on requ i red i n P . ! 9 . ! P . . . . ( ) or . ( ) . of th i s sect i on shall be submitted to the I RB w i th i n 5 work i ng days after the use of the test art i c l e . ( d ) (1) Under . . Q .. . : : . g . : . . 1 . J . . Q .?..CQ. the Pres i dent may wa i ve the pr i or consent requ i rement for the a d m i n i strat i on of an i nvest i gational new drug to a member of the armed forces i n connect i on w i th the member ' s part i c i pat i on i n a part i cul ar military operat i on. The stat u te spec i fies that on l y the Pres i dent may wa i ve i nformed consent i n th i s connect i on and the Pres i dent may grant such a wa i ver on l y if the Pres i dent determ i nes i n wr i t i ng that obta i n i ng consent: I s not feas i b l e; i s contrary to the best i nterests of the m i l i tary me m ber; or i s not i n the i nterests of nat i onal secur i ty. The statute f u rther prov i des that i n mak ing a determ i nat i on to wa i ve pr i or i nformed consent on the ground that i t i s not feas i b l e or the ground that i t i s contrary to the best i nterests of the military members i nvo l ve d , the Pres i dent shall app l y the standards and cr i ter i a that are set forth i n the re l evant FDA regu l at i ons for a wa iver of the pr i or i nformed consent requ i rements of sect i on 505 ( i ) ( 4) of the Federal Foo d , Dru g , and Cosmeti c Act ( ?. } . . . : † ! . : ? . . ?. (!) ( ).). Before such a determ i nation may be made that obtai n i ng i nformed consent from military personnel pr i or to the use of an i nvest i gational drug ( i nc l ud i ng an ant i b i ot i c or b i o l og i cal product) i n a specif i c protocol under an i nvest i gat ional new drug app l i cat i on ( IND ) sponsored by the Department of Defense ( DO D ) and l i m i ted to specific m il i tary

2 1 CF R S 0 . 2 3 (d) ( 1)( xi ) ( enhanced display) p a g e7of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0 . 2 3 (d)(1)( i ) personnel i nvolved i n a part i cu l ar military operat i on i s not feas i b l e or i s contrary to the best i nterests of the m i l i tary members i nvo l ved the Secretary of Defense must first request such a determ i nati on from the Pres i dent, and cert i fy and document to the P res i dent that the follow i ng standards and cr i ter i a conta i ned i n P . . r . 9 . . P . . . . ( ) . (J J through . ( ) ( ) . of th i s sect i on have been met. ( i ) The extent and strength of ev i dence of the safety and effectiveness of the i nvest i gational new drug i n re l at i on to the med i cal risk that cou l d be encountered dur i n g the mi l i tary operat i on supports the drug ' s adm i n i strat i on under an I ND. The military operation presents a substant i al risk that military personnel may be subject to a chem i ca l , b i o l og i cal, nuclear , or other exposure l i ke l y to prod u ce death or serious or life threaten i ng i njury or illness. There is no availab l e sat i sfactory a l ternati ve therapeut i c or prevent i ve treatment i n re l at i on to the i ntended use of the i nvestigati o n al new drug. Cond i t i on i ng use of the i nvesti gat i onal new drug on the vol untary part i c i pat i on of each member cou l d s ign i ficant l y r i sk the safety and hea l th of any i ndiv i dual member who wou l d dec l i ne i ts us e , the safety of other military personne l , and the accomp l ishment of the mil i tary miss i o n . ( v ) A du l y const i tuted i nst i tuti onal rev i ew board { I R B ) established and operated i n accordance w i th the requ i rements of p r . 9 . r . .P . . . . ( ). ( ? . ). and . ( ) . ( ) . of th i s sect i on, respons i b l e for rev i ew of the stud y , has rev i ewed and approved the i nvest i gat i onal new drug protocol and the adm i n i strat i on of the i nvestigational new drug w i thout i nformed consent. D O D ' s request i s to i nc l ude the documentat i on requi red by . † . . ? . . : . J . . 1 . ( ) . ( ) .. f .. . ! . .. . P. ! . · DOD has exp l a ine d : ( i i ) ( ii i ) { i v ) ( v i ) (A) The context i n wh ich the i nvestigational drug will be ad m i n i stere d , e. g . , the sett i ng or whether i t will be self - adm i nistered or i t will be adm in i stered by a hea l th profess i ona l ; (B) The nature of the disease or cond i t i on for wh i ch the prevent i ve or therapeut i c treatment is i ntended; and { C ) To the extent there are ex i sti ng data or i nformat i on avai l ab l e , i nformat i on on cond i t i ons that cou l d a l ter the effects of the i nvest i gat i onal drug. (vii) DOD ' s recordkeep i ng system i s capab l e of track i ng and will be used to track the proposed treatment from supp l i er to the i nd i v i dual rec i p i ent. (viii) Each member i nvo l ved in the mil i tary operat i on will be g i ve n , pr i or to the adm i n i strat i on of the i nvest i gational new drug, a spec i f i c wri tten i nformat i on sheet ( incl ud i ng i nformat i on requ i red by .J. Q .. . : . : . : J.. J . Q? ( )) concern i ng the i nvest i gat i onal new dru g , the risks and bene f i ts of i ts use, potent i al s ide effect s , and other pert i nent i nformat i on about the appropr i ate use of the product. ( i x ) Med i cal records of members i nvolved i n the m i l i tary operat i on will accuratel y document the rece i pt by members of the notificati on requi red by P . r . 9 . P. . . . . ( ) . OJ ( Y . ! D . . of th i s sect i o n . ( x ) Med i cal records of members i nvolved i n the m i l i tary operat i on will accuratel y document the rece i pt by members of any i nvest i gat i onal new drugs i n accordance w i th FDA regu l at i ons i nc l ud i ng p . . .J . ? . . . . f... . . .. . P ! r. DOD will prov i de adequate followup to assess whether there are bene f i c i al or adverse hea l th consequences that resu l t from the use of the i nvest i gat i onal product. ( x i )

21CFR5 0 . 2 3 (d)(4) ( enhanced di s pla y ) pa g e 8 of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 21CFR5 0.2 3 (d) ( 1)( xii ) (xii) DOD i s pursui ng drug deve l opment, i nc l ud i ng a t i me line, and marketing approval w i th due d i l i gence. (xiii) FDA has concluded that the i nvest i gat i onal new drug protocol may proceed subject to a dec i si on by the Pres i dent on the i nformed consent waiver request. (xiv) DOD will prov i de trai n i ng to the appropri ate med i cal personnel and pote n t i al rec i p i e n ts on the specific i nvest i gat i onal new drug to be admi n i stered pr i or to i ts use. (xv) DOD has stated and just i f i ed the t i me per i od for w h i ch the wa i ver i s neede d , not to exceed one yea r , un l ess separatel y renewed under these standards and cr i ter i a. (xvi) DOD shall have a cont i nu i ng obligat i on to report to the FDA and to the Pres i dent a n y changed c i rcumstances re l at i n g to these standards and cr i ter i a ( i nclud ing the t i me per i od referred to i n .P . r . 9.t .P . . . . ( J ( . ) { ) . of th i s sect i on) or that otherw i se m i g h t affect the determ inat i on to use an i nvest i gat i onal new drug w i thout i nformed consent. (xvii) DOD i s to prov i de public not i ce as soon as pract i cab l e and cons i ste n t w i th classificat i on requ i reme n ts through not i ce i n the FEDERAL REG I STER descr i b i ng each wa i ver of i nformed conse n t determ inat i o n , a summary of the most updated sc i ent i f i c i nformat i on on the products use d , and other perti ne n t i nformat i o n . (xviii) Use of the i nvest i gational drug w i thout i nformed consent otherw i se conforms w i th app l i cab l e l a w . (2) The du l y const i tuted i nst i t u t i onal rev i ew boar d , descr i bed i n P. r. 9 .P . . ( ). ( J ) { y). of th i s sect i o n , must i nc l ude at l east 3 nonaf f 11iated me m bers who shall not be emp loyees or officers of the Federal Government (other than for purposes of membersh i p on the I RB ) and shall be requ i red to obta in a n y necessary secur i ty clearances. Th i s I RB shall rev i ew the proposed I ND protocol at a convened meeting at wh i ch a major i ty of the members are prese n t i nc l ud i ng at l east one member whose pr i mary concerns are i n nonsc i e n tific areas and, i f feas i b l e, i nc l ud i ng a major i ty of the nonaffi l i ated members. The i nformat i on requ i red by . † . . ? . . : . 1 . 1 . ?. ( ) . { ? . l. f . .. . ! . . . P . ! . i s to be prov i ded to the Secretary of Defense for further rev i e w . (3) The du l y const i tuted i nst i t u t i onal rev i ew boar d , descr i bed i n P. r. 9 .P . . ( )( J ) { y). of th i s sect i o n , must rev i ew and approve: ( i ) The requ ired i nformat i on sheet; ( i i ) The adequacy of the p l an to d i ssem i nate i nformat i o n , i nc l ud i ng d i str i but i on of the i nformat i on sheet to potent i al rec i p i e n ts, on the i nvest i gat i onal product ( e . g . , i n forms other than wr i tte n ) ; ( ii i ) The adequacy of the i nformat i on and p l ans for i ts d i ssem i nat i on to hea l th care prov i der s , i nc l u d i ng pote n t i al s i de effects, co n trai nd i cat i ons, pote n t ial i n teract i on s , and other pert i ne n t cons i derat i ons; and An i nformed consent form as requ ired by p r . . . . ? . . Q .. f . . . . ! .. . P . . E · i n those c i rcumstances i n wh i ch DOD determ i nes that i nformed consent may be o b ta i ned from some or all personnel i nvo l ved . ( i v ) ( 4 ) DOD i s to subm i t to FDA summar i es of i nst i t u t i onal rev i ew board meetings at wh i ch the proposed protocol has been rev i ewed.

page9of t7 2 1 CF R S 0 . 2 3 ( eX s ) ( enhanced dis p la y ) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR 5 0 . 2 3 (d)( S ) ( 5 ) Noth i ng i n these cr i ter i a or standards is i ntended to preempt or l i m i t FDA's and DOD ' s author i ty or ob l i gati ons under app l i cab l e statutes and regu l at i ons. ( e ) ( 1 ) Obta i n i ng i nformed consent for i nvest i gat i onal i n v i tro d i agnost i c dev i ces used to i dent i fy chem i ca l , b i o l o g i ca l , radi o l og i ca l , or nuc l ear agents will be deemed feas i b l e un l ess, before use of the test art i c l e , both the i nvest i gator (e . g . , cli n i cal l aboratory d i rector or other respons i b l e i nd i v i dual) and a phys i c i an who i s not otherwise partic i pat i ng i n the c l i n i cal i nvestigat i on make the determ i nat i ons and l ater cert i fy i n wri t i ng all of the follow i ng: (i) The human subject is confronted by a l ife - threaten ing s i tuat i on necessi tat i ng the use of the i nvest i gational i n v i tro d i agnost i c dev i ce to i dentify a chem i ca l , b i o l og i ca l , rad i o l og i ca l , or nuclear agent that wou l d suggest a terror i sm event or other pub l i c hea l th emergency. Informed consent cannot be obta i ned from the subject becaus e : (A) There was no reasonab l e way for the person d i rect i n g that the speci men be collected to kno w , at the t i m e the speci men was collected, that there wou l d be a need to us e the i nvest i gat i onal i n v i tro d i agnost i c dev i ce on that subject ' s spec i me n ; and { B ) T i me is not suffic i ent to obta i n consent from the subject w i thout r i sk ing the l ife of the subject. T i me i s not suffic i ent to obta i n consent from the subject's l egally author i zed representat i ve. There is no c l eared or approved ava i l ab l e a l ternative method of d i agnosi s , to i dent i fy the chem i ca l , b i o l og i cal, rad i o l og i cal, or nuc l ear agent that prov i des an equal or greater l i kel i hood of sav i ng the life of the subject. ( i i ) ( i i i) ( i v ) (2) I f use of the i nvest i gat i onal dev i ce i s , i n the op i n i on of the i nvest i gator ( e . g . , c l i n i cal laboratory d i rector or other respons i b l e person ) , requi red to preserve the l ife of the subject, and t i me is not suffic i ent to obta i n the i ndependent determ i nat i on requ i red i n p r . 9 . r . P . . ( 20) of this sect i on i n adva n ce of us i n g the i nvest i gat i onal dev i ce, the determ i nations of the i nvesti gator shall be made an d , w i th i n 5 work i ng days after the use of the dev i c e , be rev i ewed and eva l uated i n wri t i ng by a phys i c i an who i s not part i c i pat i ng i n the c l i n i cal i nvest i gat i o n . (3) The i nvesti gator must subm i t the wr i tten certificat i on of the determ i nat i ons made by the i nvest i gator and an i ndependent phys i c i an requ i red i n P. 9 . r . . P . .. ( ) . { n_ or . ( ) . ( ? . ) . of th i s sect i on to the I RB and FDA w i th i n 5 work i ng days after the use of the dev i ce. (4) An i nvest i gator m ust disclose the i nvest i gat i onal status of the i n v i tro d i agnost i c dev i ce and what is known about the performance character i st i cs of the dev i ce i n the report to the subject's hea l th care prov i der and i n any report to public health author i t i es. The i nvestigator must prov i de the I RB w i th the i nformat i on requi red i n † .. . ? . Q : . ?.:? . . ( except for the i nformat i on descr i bed i n † . . ?. Q : . ?.:? . . ( ) ( ) ) and the procedures that will be used to prov i de this i nformat i on to each subject or the subject ' s l egally author i zed representat i ve at the t i me the test resu l ts are prov i ded to the subject ' s hea l th care prov i der and pub l i c hea l th author i t i es. (5) The I RB i s respons i b l e for ensur i ng the adequacy of the i nformat i on requi red i n . . ! 2 . . ? . 9 : . ?.:? . . ( except for the i nformat i on descr i bed i n † . .. Q : . . ? . . ( ). ( ) ) and for ensur i ng that procedures are i n p l ace to prov i de this i nformat i on to each subject or the subject's l egally author i zed representat i ve.

2 1 CF R s o . 2 4(a) ( s ) (enhanced dis p lay ) paget0 of t7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0 . 2 3 ( e )( 6 ) ( 6 ) No State or pol i t i cal subd i vis i on of a State may establish or cont i nue i n effect any l a w , ru l e , regu l at i on or other requi rement that i nformed consent be obta i ned before an i nvest i gat i onal i n v i tro d iagnost i c dev i ce may be used to i dentify chem ical, b i o l og i ca l , radi o l og i ca l , or nuc l ear agent i n suspected terrorism events and other potent i al p u blic hea l th e mergenci es that i s different fro m , or i n add i t i on to, the requi rements of this regu l at i o n . f . . . E ! . i . ?. . ?. . ?.! Jan. 27, 198 1 , as amended at . ? . . .E. . . ? ? . . ! . !.t Dec. 21, 1990 ; . . .E.. . . ? . ! Jan. 5 , 1999; . . E t:! . . ?. . ? . . † ! ! Oct. 5 , 1999 ; ? J .. . E . !i f. ? ? . ! . June 7, 2006; ? .. E t:! . . ? . ? ! . June 24, 2011] † 5 0. 24 Exception fro m informed c onsent requirements fo r emer g ency research. (a) The I RB respons i b l e for the rev i e w , approva l , and cont i nu i ng rev i ew of the clin ical i nvestigati on descr i bed i n th i s sect i on may approve that i nvestigati on w i thout requi r i n g that i nformed consent of all research subjects be obta i ned i f the I RB (w i th the concurrence of a l i censed phys i c ian who is a member of or consu l tant to the I RB and who i s not otherwise parti c i pat i ng i n the c l i n i cal i nvest i gati on) finds and documents each of the follow i ng: (1) The human subjects are i n a life - threaten i ng s i tuat i o n , avai l ab l e treatments are unproven or unsatisfactor y , and the collect i on of valid sc i entific ev i dence, wh ich may i nc l ude ev i dence obta i ned through random i zed p l acebo - controlled i nvest i gat i on s , i s necessary to determ i ne the safety and effect i veness of part i cu l ar i ntervent i ons. (2) Obta i n i ng i nformed consent is not feas i b l e because: ( i ) The subjects will not be ab l e to g i ve the i r i nformed consent as a resu l t of the i r med i cal condit ion; The i ntervent i on u nder i nvest i gat i on must be adm i n i stered before consent from the subjects' l egal l y authorized representat i ves i s feas i b l e; and There is no reasonab l e way to i dent i fy prospect ive l y the i nd i v i dua l s l i ke l y to become e l i g i b l e for part i c i pat i on i n the cl i n i cal i nvest i gat i o n . ( i i ) ( i i i) (3) Part i c i pat i on i n the research ho l ds out the prospect of d i rect benefit to the subjects because: (i) Subjects are fac i ng a life - threateni ng s i tuat i on that necess i tates i ntervent i on; ( i i ) Appropr i ate an i mal and other precl i n i cal stud i es have been conducted, and the i nformat i on der i ved from those stud i es and re l ated ev i dence support the potent i al for the i ntervent i on to prov i de a d i rect bene f i t to the i nd i v i dual subject s ; and ( ii i ) R i sks assoc i ated w i th the i nvest i gat i on are reasonab l e i n rel at i on to what i s known about the med i cal cond i t i on of the potent i al c l ass of subject s , the risks and benefits of standard therap y , if an y , and what is known about the risks and benefits of the proposed i ntervent i on or act i v i t y . (4) The c l i n i cal i nvesti gat i on cou l d not pract i cab l y be carr i ed out w i thout the wa i ve r . (5) The proposed i nvest i gational p l an defines the l ength of the potent i al therapeut i c w i ndow based on sc i ent i fic ev i denc e , and the i nvest i gator has comm i tted to attempt i ng to contact a l egally author i zed representat i ve for each subject w i th in that w i ndow of ti me an d , if feas i b l e , to ask i n g the l egally author i zed representat i ve contacted for consent w i th i n that w i ndow rather than proceed i ng w i thout consent. The i nvest i gator will summar i ze efforts made to contact l egally author i zed representat i ves and make th i s i nformat i on ava i l ab l e to the I RB at the ti me of cont i nu i ng rev i ew.

2 1 CF R S 0 . 24( c ) (enhanced dis p lay ) pagel1of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR 5 0 . 2 4 ( a )( 6 ) ( 6 ) The I RB has rev i ewed and approved i nformed consent proce d ures and an i nformed consent document cons i stent w i th † . . . † . Q : . ? . - These procedures and the i nformed consent document are to be used w i th subjects or the i r l egally author i zed representatives i n s i tuat i ons where use of such procedures and documents i s feas i b l e . The I RB has rev i ewed and approved procedures and i nformat i on to be used when prov i di ng an opportun i ty for a fam i l y member to object to a subject ' s part i c i pat i on i n the c l i n i cal i nvest i gat i on cons i stent w i th P. ! ! 9.r . P . . . ( ). Q l (Y.). of th i s sect i on. ( 7 ) Add i t i onal protect i ons of the r i ghts and we l fare of the subjects will be prov i de d , i ncl ud i n g , at l east: ( i) Consu l tati on ( incl ud i n g , where appropr i at e , consu l tati on carr i ed out b y the I RB ) w i th representatives of the commun i t i es i n wh ich the clin i cal i nvesti gat i on will be conducted and from whi ch the subjects will be drawn; Public d i sc l osure to the commun i t i es in wh i ch the c l i n i cal i nvest i gati on will be conducted and from whi ch the subjects will be drawn, pr i or to i n i t i at i on of the cl i n i cal i nvestigati o n , of p l ans for the i nvestigati on and i ts risks and expected benefit s ; Public d i sc l osure of suffic i ent i nformat i on follow i ng comp let i on of the c l i n i cal i nvest i gat i on to appr i se the commun i ty and researchers of the stud y , i nclud i ng the demograph i c characterist i cs of the research popu l at i o n , and i ts res u l ts; Establis h ment of an i ndependent data mon i tor i ng comm i ttee to exercise overs i ght of the cl i n i cal i nvest i gati o n ; and ( v ) I f obta i n i ng i nformed consent i s not feas i b l e and a l egally authorized representative is not reasonab l y availab le, the i nvest i gator has com m i tted, i f feas i b l e, to attempt i ng to contact w i th i n the therapeut i c w i ndow the subject ' s fam i l y me m ber who is not a l egally author i zed representative , and ask i ng whether he or she objects to the subject's partic i pat i on in the cl i n i cal i nvest i gati on. The i nvest i gator will su m mar i ze efforts made to contact fam i l y members and make this i nformat i on ava i l ab l e to the I RB at the t i me of cont i nu i ng rev i e w . ( i i ) ( i i i) ( i v ) (b) The I RB i s respons i b l e for ensuri n g that procedures are i n p l ace to i nfor m , at the earliest feas i b l e opportun i t y , each subject, or if the subject rema i ns i ncapac i tate d , a l egally author i zed representat i ve of the subject, or if such a representat i ve is not reasonab l y availab l e , a family member , of the subject ' s i nclusi on i n the c l i n i cal i nvest i gat i o n , the deta i l s of the i nvest i gat i on and other i nformat i on conta i ned i n the i nformed consent document. The IRB shall a l so ensure that there i s a procedure to i nform the subject , or if the subject rema i ns i ncapac i tate d , a l egally author i zed representat i ve of the subject, or i f such a representat i ve i s not reasonably availab l e , a family membe r , that he or she may d i scont i n ue the subject ' s part i c i pat i on at any t i me w i thout pena l ty or l oss of benefits to wh i ch the subject i s otherwise ent i t l e d . I f a l egally author i zed representat i ve or family member i s to l d about the cl i n i cal i nvest i gat i on and the subject ' s cond i t i on improves, the subject i s a l so to be i nformed as soon as feas i b l e . I f a subject is entered i nto a cl i n i cal i nvest i gati on w i th wai ved consent and the subject d i es before a l egal l y authorized representat i ve or family me m ber can be contacte d , i nformat i on about the cl i n i cal i nvest i gat i on i s to be prov i ded to the subject ' s l egally authorized representat i ve or fami l y membe r , i f feas i b l e . (c) The I RB determ i nat i ons requ i red by P. ! ! 9.r . .P . . . { ) of this sect i on and the documentat i on requ i red by P . . r . 9 . r . P . . ( ). of this sect i on are to be reta i ned by the I RB for at l east 3 years after comp l et i on of the clin i cal i nvest i gat i o n , and the records shall be access i b l e for i nspect i on and copy i ng by FDA i n acc o rd a nee w i th . † . . . . :J.J . . { J . 9 . f. . . - ! . - - P ! r.

21CFR5 0 . 25( a ) ( 8 ) (enhanced di s p l a y ) page12 of t7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 cFR s o . 24(d) (d) Protoco l s i nvo l v i ng an excepti on to the i nformed consent requi rement under this sect i on must be performed under a separate i nvesti gat i onal new drug app l i cat i on ( IND ) or i nvest i gat i onal devi ce exempt i on ( I DE ) that c l ear l y i dent i fies such protoco l s as protoco l s that may i nclude subjects who are unab l e to consent. The submiss i on of those protoco l s i n a separate I ND/IDE i s requ i red even if an I ND for the same drug product or an I DE for the same devi ce a l ready ex i sts. App l i cat i ons for i nvest i gat i ons under this sect i on may not be subm i tted as amendments under † . † . . . . ? . : . Q . or . . ? . : . . ? . . 2f. . . . ! ... . . P ! . . · (e) I f an I RB deter m i nes that i t cannot approve a c l i n i cal i nvest i gati on because the i nvestigati on does not meet the cr i ter i a in the excepti on prov i ded under P. 9 E P . . . . ( ) . of this sect i on or because of other re l evant ethi cal concern s , the IRB must document i ts find i ngs and prov i de these find i ngs prompt l y i n wr i ti ng to the cl i n i cal i nvest i gator and to the sponsor of the cl i n i cal i nvest i gat i o n . The sponsor of the clin i cal i nvest i gat i on must pro m pt l y disclose th i s i nformat i on to FDA and to the sponsor' s c l i n i cal i nvest i gators who are part i c i pat i ng or are asked to part i c i pate i n this or a substant i ally equ i va l ent cl i n i cal i nvest i gat i on of the sponso r , and to other I RB's that have bee n , or ar e , asked to rev i ew this or a substant i ally equ i va l ent i nvest i gat i on b y that sponsor. [ 1 .. . f. B . . ? 1 . ? ? . ! Oct. 2, 1996] † 5 0 . 2 5 Elements of informed c onsent. (a) Basic elements of informed c o ns e nt. I n seek i ng i nformed consent, the follow i ng i nformat i on shall be prov i ded to each subject: (1) A statement that the study i nvolves researc h , an exp l anat i on of the purposes of the research and the expected durat i on of the subject's part i cipati o n , a descr i pt i on of the procedures to be followed, and i dent i ficat i on of any procedures wh i ch are exper i mental. (2) A descr i pt i on of any reasonably foreseeab l e risks or discomforts to the subject. (3) A descr i pt i on of any benef i ts to the s u bject or to others whi ch may reasonab l y be expected from the research. (4) A d i sc l osure of appropr i ate a l ternati ve procedures or courses of treatment, if an y , that m i ght be advantageous to the subject. (5) A statement descr i b i ng the exten t , if an y , to wh i ch confident i al i ty of records i dentify i ng the subject will be ma i nta i ned and that notes the poss i bil i ty that the Food and Drug Adm i nistrat i on may i nspect the records. (6) For research i nvo l v i ng more than m i n i mal risk, an exp l anat i on as to whether any compensat i on and an exp l anat i on as to whether any med i cal treatments are ava i l ab l e i f i njury occurs an d , if s o , what they consist of, or where further i nformat i on may be obta i ned. ( 7 ) An exp l anat i on of whom to contact for answers to pert i nent quest i ons about the research and research subjects' r i ght s , and whom to contact i n the event of a research - re l ated i njury to the subject. ( 8 ) A statement that part i c i pat i on i s vo l untar y , that refusal to partic i pat e will i nvo l ve no pena l ty or l oss of benef i ts to wh i ch the subject is otherw i se ent i t l e d , and that the subject may d i scont i nue part i c i pat i on at any ti me w i thout penalty or l oss of benefits to w h i ch the subject i s otherw i se ent i t l ed.

2 1 CF R S 0 . 27( bX2 ) ( enha n ced display ) page13of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S0.25(b) (b) Additional elements of informed consent. When appropr i at e , one or more of the follow i ng e l ements of i nformat i on shall a l so be prov i ded to each subject: (1) A stateme n t that the pa n i cu l ar treatment or procedure may i nvo l ve r i sks to the subject ( or to the embryo or fetus , i f the subject i s or may become pregna n t ) wh i ch are current l y unforeseeab l e. (2) A n t i c i pated c i rcumstances under wh i ch the subject ' s part i c i pat i on may be termi nated by the i nvest i gator w i thout regard to the subject ' s conse n t. (3) Any add i t i onal costs to the subject that may resu l t from part i c i pat i on i n the research. (4) The consequences of a subject ' s dec i s i on to w i thdraw from the research and procedures for order l y term i nat i on of pa n i c i pat i on by the subject. (5) A stateme n t that s i gnifica n t new find i ngs devel oped dur i n g the course of the research wh i ch may re l ate to the subject ' s w i llingness to co n t i nu e pa n i c i pat i on will be prov i ded to the subject. (6) The approx i mate number of subjects i nvo l ved i n the study. (c) When seek i ng i nformed conse n t for applicab l e cl i n i cal tr i a l s , as defined i n . . : . . : ... . G > . ( 1 1 ( ) .. the follow i ng stateme n t shall be prov i ded to each cl i n i cal tr i al subject i n i nformed consent doc u me n ts and processes. Th i s will not i fy the cl i n i cal tr i al s u bject that clin i cal tr i al i nformat i on has been or will be subm i tted for i nclus i on i n the cl i n i cal tr i al reg i stry databank under paragraph Q) of sect i on 402 of the Pub l i c Hea l th Serv i ce Act. The statement i s: HA descr i pt i on of th i s c li n i cal tr i al will be availab l e on !!P. l ! . : . 9. . ! ! !. .! . ! r . . ! . : . g g . '!! as requ i red by U . S . Law. Th i s Web s i te will not i nc l u de i nformat i on that can i dent i fy you. At most, the Web s i te will i nclude a summary of the resu l ts. You can search th i s Web s i te at a n y t i me: (d) The i nformed conse n t requ i reme n ts i n these regul at i ons are not i n tended to preempt any applicab l e Federal, Stat e , or l ocal l aws wh i ch requ i re add i t i onal i nformat i on to be d i sc l osed for i nformed conse n t to be l egally effect i ve. (e) Nothi ng i n these regu l at i ons i s i n tended to l i m i t the a u thor i ty of a phys i c i an to prov i de emergency med i cal care to the exte n t the phys i c i an i s perm i tted to do so under app l i cab l e Federa l , State, or l ocal l aw. ( 1 . . . E ! . i . !! . ?. . ! Jan. 27, 198 1 , as amended at ? . .E . ! i . ?!.. ! Jan. 4 , 2011] † 5 0 . 2 7 Documentation of informed consent. (a) Except as prov i ded i n † . . ? . † . : . J . . Q . . ( !?, ) . . i nformed consent shall be documented b y the use of a wr i tten conse n t form approved by the I RB and s i gned and dated b y the subject or the subject ' s l egally a u thor i zed representati ve at the t i me of conse n t. A copy shall be g i ven to the person s i gn i ng the for m . (b) Except as prov i ded i n † .. . ? . † . : . J . .Q .. ( !?, ) . . the consent form may be e i ther of the follow i n g : (1) A wr i tten consent document that embod i es the e l ements of i nformed conse n t requ i red by † . . . ?. Q . : ?.: · Th i s form may be read to the subject or the subject ' s l egally authorized representati ve, b u t, i n any event, the i nvest i gator shall g i ve e i ther the subject or the represe n tative adequate oppo n un i ty to read i t before i t i s s i gned. (2) A short form wr i tten consent doc u me n t stat i ng that the e l ements of i nformed conse n t requ i red by † . . ? Q : . ?.: ? . have been prese n ted orally to the subject or the subject's l egally a u thor i zed represe n tat i ve. When th i s method i s use d , there shall be a w i tness to the oral prese n tat i o n . A l s o , the I RB shall approve a wr i tten s u mmary of what i s to be sa i d to the subject or the representati ve. On l y the short

21CFR5 0 . 52( c ) (enhanced dis p lay ) page 1 4of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR 50.SO form i tself is to be s i gned by the subject or the representat i ve. Howeve r , the w i tness shall s i gn both the short form and a copy of the s u mmar y , and the person actually obta i n i n g the consent shall s i gn a copy of the su m mar y . A copy of the summary shall be g i ven to the s u bject or the representat i ve i n add i t i on to a copy of the short for m . ( 1 . . . f. . B . . ! ! ?. , ?. , Jan. 27, 198 1 , as amended at . .1. . . f. . B . . ? ! . ? . . . 9 , . Nov. 5 , 1996] S ubpart C [R e served] S ubpart D - Add i tional S afeguards for Children in Clinical Inv e stigations S o urc e : . . . E . . ?. 9 . ? . . . . Apr. 2 4 , 2001 , un l ess otherw i se noted. † S O . SO IRB duti e s . I n add i t i on to other respons i bilit i es ass i gned to I RBs under t h i s . l? . r.: ! .. . . . P . .. . ? . † . .9. .. . l . . 9 . . . I? . ! . . each I RB must rev i ew cl i n i cal i nvestigati ons i nvolv i ng ch ildren as subjects covered by th i s subpart D and approve on l y those c l i n i cal i nvest i gat i ons that satisfy the cr i ter i a descr i bed i n † . . . ?. 9 . : ?. J . .. † . . . ?. 9 : . ? . ? . . or † .. . ?. 9 : . ?. and the cond i t i ons of all other applicab l e sect i ons of t h i s subpart D. † S O . St Clinical inv e stigation s not involving greater than minimal risk. Any cl i n i cal i nvest i gat i on w i th in the scope descr i bed i n _ † . † . . . ? . 9 : . J . . and . ? . † : . J . . 9 . . J . .. f . ! . ! .. b . .P . ! . i n wh ich no greater than m i n i mal r i sk to ch ildren i s presented may i nvo l ve ch il dren as subjects on l y i f the I RB fmds that: (a) No greater than m i n i mal risk to ch i l dren is presente d ; and (b) Adequate provis ions are made for solic i t i n g the assent of the chi ldren and the permiss i on of the i r parents or guard i ans as set forth i n † . . . ? . 9 : . ? ? : f? . . . f... ] ? . . ? . . J . 1 Feb. 26, 2013] † S 0 . 52 Clinical inve s t i gations invo l ving greater than minimal risk but presenting the pro s pect of direc t benefit to ind i vidual s ubject s . Any c l i n i cal i nvest i gat i on w i th in the scope descr i bed i n . † . † . . . ? . 9 : . J .. and . ? . † : . J . . 9 . . J . . . f . ! . ! .. b . . P . ! . i n wh ich more than m i n i mal r i sk to ch ildren i s presented by an i ntervent i on or procedure that ho l ds out the prospect of d i rect bene f i t for the i nd i v i dual subject , or by a mon i tor i ng procedure that i s l i kely to contr i bute to the subject's wel l - be i n g , may i nvo l ve children as subjects on l y i f the I RB finds that: (a) The r i sk is just i fied by the anti c i pated bene f i t to the subject s ; (b) The re l at i on of the anti c i pated bene f i t to the risk is at l east as favorab le to the subjects as that presented by ava i l ab l e a l ternati ve approaches; and (c) Adequate provis ions are made for solic i t i n g the assent of the chi ldren and permiss i on of the i r parents or guard i ans as set forth i n . † . . . ? . . Q : . ?.? . · ( . . r n . 9 . . ? ' Apr. 2 4 , 2001. as amended at ?. . . . f.. . ' 3 J . ? . . ? . . ?., Feb. 26, 2013]

2 1 CF R s o . 54( b ) ( 2 )(lli) (enhanced dis p lay ) paget5of t7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0. 53 † 5 0 . 5 3 Clinical inve s t i gations inv o l ving greater than minimal risk and no prospect of direct benefit to ind i v i dual s ubjects, but like l y t o y i e ld g eneralizable knowledge about the sub j ect s ' disorder or condition. Any c l i n i cal i nvest i gat i on w i th in the scope descr i bed i n . † . † . . ? .Q:.J. . and . ? . † :.J . . 9 . .J . . f.. . . ! . . b . . P. . . i n wh ich more than m i n i mal r i sk to ch ildren i s presented by an i ntervent i on or procedure that does not ho l d out the prospect of d i rect benef i t for the i nd i v i dual subject, or by a mon i tor i ng procedure that i s not like l y to contr i bute to the well - be i ng of the subject, may i nvo l ve children as subjects on l y i f the I RB finds that: ( a ) The r i sk represents a m i nor i ncrease over m i n i mal risk; { b ) The i ntervent i on or proce d ure presents experi ences to s u bjects that are reasonab l y commensurate w i th those i nherent in the i r actual or expected med i ca l , denta l , psycho l og i ca l , soc i a l , or ed u cat ional s i tuat i on s ; ( c ) The i ntervent i on or proce d ure is li ke l y to y i e l d generalizab l e know l edge about the subjects' d i sorder or cond i t i on that i s of vital i mportance for the understand ing or ameliorat i on of the subjects' d i sorder or cond i t i o n ; and { d ) Adequate provis ions are made for solic i t i n g the assent of the chi ldren and permiss i on of the i r parents or guard i ans as set forth i n . † . . . ? . . 9 . : . ? . ? . · £ . . f.. . 9 . ? . ! ! 1 Apr. 2 4 , 2001, as amended at .! . . . f.. ) . ? . . . ?., Feb. 26, 2013] † 5 0 . 5 4 Clinical inve s t i gations not otherwise approvable that present a n opportunity to understand, prevent, o r alleviate a seriou s probl e m affecting the health o r welfare of children. I f an I RB does not be l i eve that a cli n i cal i nvest i gat i on w i th i n the scope descr i bed i n † . † . . . ? . . Q : . 1 . and . ? . . : . J . . 9 . . J .... f . ! . ! .9 . . .I?. . . and i nvo l v i ng children as subjects meets the requi rements of † . . ?. Q . . - . ?. J . . . † .. . ?. 9 : . ? . ?. : . or † . . . ? . 9 : . † . , the c l i n i cal i nvest i gat i on may proceed on l y if: (a) The I RB fmds that the c l i n i cal i nvest i gat i on presents a reasonab l e opportun i ty to further the understand i n g , prevent i o n , or allev i at i on of a seri ous prob l em affect in g the hea l th or we l fare of ch i l dre n ; and { b ) The Commiss i oner of Food and Drug s , after consu l tat i on w i th a panel of experts i n pert i nent discip l i nes ( for examp l e : sc i enc e , med i c i n e , educat i o n , ethi c s , l a w ) and follow i ng opportun i ty for pub l i c rev i ew and commen t , determ i nes e i ther : (1) That the c l i n i cal i nvest i gat i on i n fact sat i sf i es the cond i t i ons of . † . . . ?.9 . : . ? . 1 , † . . . ?. 9 : . ?.?.. or † . . . ?.9 . : . ? . .. as applicab l e , or (2) That the follow i ng cond i t i ons are met: ( i ) The clin i cal i nvest i gation presents a reasonab l e opportun i ty to further the understand i n g , prevent i o n , or allev i at i on of a ser i ous prob l em affectin g the hea l th or we l fare of children ; The clin i cal i nvest i gat i on will be conducted i n accordance w i th sound ethi cal pr i nci p l e s ; and Adequate prov i s i ons are made for so l i c i t i ng the assent of ch i l dren and the perm i ss ion of the i r parents or guard i ans as set forth i n † .. . ?.9 . . - . ?.? . · ( i i ) ( ii i ) £ - . f.. . 9 . . ? ! ! , Apr. 2 4 , 2001, as amended at .! . . . E. ) . ? . . . ?., Feb. 26, 2013]

21CFR5 0 . SS (g) (enhanced display) pa g e t6of t7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR S 0. 55 † 5 0 . 5 5 Requirements fo r permi s s i o n b y parents o r guardians and for assent b y childre n . (a) I n add i t i on to the determ i nat i ons requ i red under other applicab l e sect i ons of th i s subpart D , the I RB must determ i n e that adequate provis i ons are made for so l i c i t i ng the assent of the children when i n the judgment of the I RB the c h i l dren are capabl e of prov i di ng assent. (b) I n determ i n i ng whether children are capabl e of prov i d i ng assen t , the I RB must take i nto account the age s , matur i t y , and psycho l og i cal state of the children i nvo l ve d . Th i s judgment may be made for all children to be i nvo l ved i n cl i n i cal i nvestigat i ons under a part i cu l ar protoco l , or for each child, as the I RB de e ms appropr i ate. (c) The assent of the children i s not a necessary cond i tion for proceed i ng w i th the c l i n i cal i nvesti gat i on i f the I RB determ i nes: (1) That the capabil i ty of some or all of the ch i l dren is so lim i ted that they cannot reasonab l y be consulte d , or (2) That the i ntervent i on or procedure i nvo l ved i n the cl i n i cal i nvest i gat i on ho l ds out a prospect of d i rect benef i t that is i mportant to the hea l th or wel l - bei ng of the children and i s availab l e on l y i n the context of the cl i n i cal i nvest i gat i on . (d) Even where the I RB determ i nes that the subjects are capabl e of assent i n g , the I RB may still wai ve the assent requi rement i f i t finds and documents that: (1) The clin i cal i nvesti gat i on i nvo l ves no more than m i n i mal r i sk to the subject s ; (2) The wa i ver will not adverse l y affect the r i ghts and we l fare of the subjects; (3) The clin i cal i nvesti gat i on cou l d not pract i cab l y be carr i ed out w i thout the wa i ver; and (4) Whenever appropr i at e , the subjects will be prov i ded w i th add i t i onal perti nent i nformat i on after part i c i pat i o n . (e) I n add i t i on to the determ i nat i ons requ i red under other applicab l e sect i ons of th i s subpart D , the I RB must determ i n e , i n accordance w i th and to the extent that consent is requ i red under part 5 0 , that the permiss i on of each child ' s parents or guard i an is granted. (1) Where parental permiss i on i s to be obta i ne d , the I RB may find that the permiss i on of one parent is suffic i ent for c l i n i cal i nvest i gati ons to be conducted under † . . ? . 9 : . ? 1 . or . † .. . ?. 9 : ? ? . · ( 2 ) Where cl i nical i nvest i gati ons are covered by . † . . ?. 9 : † . . or † .. . ?. 9 : . and perm i ss i on i s to be obta i ned from parent s , both parents must give the i r perm i ss ion un l ess one parent i s deceased, unknow n , i ncompetent, or not reasonab l y availab l e , or when only one parent has l egal respons i bil i ty for the care and custody of the child . ( f ) Perm i ss ion by parents or guard i ans must be documented i n accordance w i th and to the extent requ i red by † .. . ? . . Q . . . ?.Z : · ( g ) When the I RB determ i nes that assent is requi red, i t must a l so determ i ne whether and how assent must be documented. [ . . f. B . 9 . ? . ! Apr. 2 4 , 2001, as amended at ?. . . . f. . 13. J . ? . . . ?.! Feb. 26, 2013]

2 1 CF R S 0 . 56( b X4) (enhanced display) page 1 7of 1 7 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art50 {u p to d ate as o r 9/'2.5/202 5 J Protection of Human S ubjects 2 1 CFR5 0 . 5 6 † 5 0 . 56 W a rds. (a) Ch i ldren who are wards of the State or any other agenc y , i nst i t u t i o n , or ent i ty can be i nc l uded i n c l i n i cal i nvest i gat i ons approved under † . . ?. Q . . . ? . . or † .. . ? . 9 : . ?. on l y if such c l i n i cal i nvest i gations ar e : (1) Re l ated to the i r status as wards; or (2) Conducted i n schoo l s , camps, hosp i ta l s, i nst i t u t i ons, or s i mi l ar sett i ngs i n wh i ch the major i ty of ch i ldren i nvo l ved as subjects are not wards. (b) I f the clin i cal i nvest i gat i on i s approved u nder p 9 . . . P . . ( ) of th i s sect i o n , the I RB must requ i re appo i ntment of an advocate for each ch i l d who i s a ward. (1) The advocate will serve i n add i t i on to any other i nd i v i dual act i ng on behalf of the child as guard i an or i n l oco parent i s. (2) One i nd i v i dual may serve as advocate for more than one c h i l d. (3) The advocate must be an i nd i v i dual who has the background and exper i ence to act i n , and agrees to act i n , the best i nterest of the child for the durati on of the child's part i c i pat i on i n the clin i cal i nvest i gat i o n . (4) The advocate must not be assoc i ated i n any way ( except i n the ro l e as advocate or member of the I RB ) w i th the c l i n i cal i nvest i gat i o n , the i nvest i gator(s ) , or the guard i an organizat i o n .

Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards page tof13 21CFR5 6 ( enhanced di s pla y ) 2 1 CFR P art 5 6 ( S e pt . 2 5 , 202 5 ) Th i s content is from the eCFR and i s authori tat i ve but u nofficia l . Title 2 1 - Food and Drugs Chapter I - F o od and Drug Admini s tration, Department of Health and Human Serv i c es S ubchapter A - General Part 5 6 Institutional Review Boards S ubpart A - - E . . .P.! . 2Y . ! . .! g . - † 5 6 . 1 0 1 9 . P . . : . † 5 6 . 1 02 .P. . . - . ! ! . 2 . . . : . † 5 6 . 1 03 . 9 . . ! E9 . . . - . ! . 9 . . . . ! . . . b ! . . . . ! . R : . .! .Y . . ! . . . ! . . E . . 9 . ! E . : . † 5 6 . 1 04 - P. ! . 2 . . - . f . 2 . . . ! . R : . . 9 . . ! . - - - . : . † 5 6 . 1 05 Y.Y . . . !Y . . . . 2 . f . .. . ! . R . . t 9 . . ! r . - - ! : . S ubpart B . 9 . . . 9 . . . ! . . ! . . ! 9 . . . . . . . . P . E † 5 6 . 1 06 . B . 9 . ! . ! . ! ! . 9 . . . : . † 5 6 . 1 07 . ! . R . . . . . . . ! . b . ! P . : . . . ! . S ubpart C . ! . . ... . ! .. 2 . i . . . . . . Q . P . ! ! . 2 . . - † 5 6 . 1 0 8 . ! . R . . . f . . . ! ! . 2 . . . . † 5 6 . 1 09 . ! . R . . . E Y . ! . . . Q . f . .. † 5 6 . 1 1 0 . . P . . ! . . . . Y . ! . . .. . 9 . . P r ! . ! . 2 . . . : . . ? . . ! . . : . . P . 2 . £ - . . . . f 2 . . . . . ! . ... ! n . . .. . 2. f .. . . - - 9 . bJ .Y . . 2 . 1 . x ! n 9 . . n 2 ... . 2 . J . n . E . . : . . . ! . . ! . . . ! . . E . ! . . . t. . . . f 2 E ... . ! . . 2 . r . . b . . . 9 . . ..! . .. P P . 2Y . . . .. !. † 5 6 . 1 1 1 . 9 . E . ! . ! . ! . . . f 2 . . . ! . R . . P P . 9.Y . . . ! . . . 2f. . . !. † 5 6 . 112 . B Y . . ! --- .Y. . . ! . . ! . . ! ! ! . Q . . : . E . . : . † 5 6 . 1 13 . . . P . . . ! . 2 . . . 2 . . . . ! . . ! . . ! ! . 2 . . . 2f . . ! . R . . P P . E2Y . . . ! . . . 2f . . !. . E . . : . † 5 6 . 1 1 4 . 9 . . 2 2 . P . . ! ! . Y . .. . E . . : . S ubpart D . R . 2 . ! . Q .. . . . . R P Q E ! . † 5 6 . 1 15 . ! . R . . . . 2 .! . . : . S ubpart E A . . . ! . . ! ! ! . . . !Y . . A . . ! 2 . . . f 2 . . . N . 2 . . 9 . . P ! . ! . g - . † 5 6 . 1 20 . . . . . . . . ! . . ! ! ! . ! . . ! Y . . . .. . ! . ! . 2 . . . : . † 5 6 . 1 2 1 .P . . ! . . 9 . . . ! . ! . f. - . ! . . 2 . f. . . . . . . ! . B . .. ! . . . . . . . ! . . . ! ! ! ! . 2 . . : . † 5 6 . 1 22 . P . . . . ! . ! . . ! . . 9 . ! . 2 . . . . . 2 f .. ! D f E . . ? . . ! . . . 9 . . . . . ! . 9 . . . ! Y . 2 ! ! . 2 . . : . † 5 6 . 1 23 . B . ! . . . ! . . . ! . . Q . f ... . . .. . ! . . . . 2 r . . J . ! . ! . ! ! . . . : . † 5 6 . 1 24 A ! . . ! 2 . .. . ! ! r . ! . . !Y . . 2 ! . .. 9 . . .!. . ! g - . ! . ! . . . ! q . . ! . ! . ! ! . . . : . P ART 5 6 - IN STITUTIONAL REVIEW BOARDS Authority: . ? . 1 ... . '. : . 9 : . . . . ? . 1 .. 4 . .. 4 . † .. . 4. .. . 4 . .. . . ?. 9 .. . . ?.9 ? . † ]. _ , . ?.? . . . . ? . . . . ?. ? . . . . 9 .. . 9 - . Q f . . . 9 .. . . 9 ! .. . † . Q j _, . . Q . : † . Q . .. ?. J . .. ?. . J . . ; 4 . ? . .. . '. : . 9 . : . . ?. J . . † .. ?.4. J . .. ? . ?? . ·

21CFR5 6 . 1 02(b) ( 8 ) ( enhanced di s pla y ) p a g e2of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 5 6 . 1 01 S o urc e : - -- - -- . ? .. Jan. 2 7 , 198 1 , u n l ess otherw i se noted. S ubpart A - General Provi s ions † 5 6 . 1 0 1 S c op e . (a) Th i s part conta i ns the general standards for the compos i t i on, operat i o n , and respons i b i l i ty of an I nst i tuti onal Rev i ew Board ( I R B ) that rev i ews cl i n i cal i nvestigati ons regu l ated by the Food and Drug Adm in i strat i on under sect i ons SOS ( i ) and 520 ( g ) of the act, as well as cl i n i cal i nvesti gat i ons that support applicat i ons for research or market i ng permits for products regul ated by the F ood and Drug Adm in i strat i o n , i ncludi ng foods, i ncl ud i ng d ietary supp l ements, that bear a nutr ient content c l a i m or a hea l th cla i m , i nfant formu l as, food and co lor add i t i ves, drugs for hu man us e , med i cal dev i ces for human use, b i o l og i cal products for human us e , and e l ectron i c product s . Compl i a n ce w i th th i s part is i ntended to protect the r i ghts and we l fare of human subjects i nvolved i n such i nvestigati on s . (b) References i n this part to regu l atory sect i ons of the Code of Federal Regu l at ions are to chapter I of t i t l e 2 1 , un l ess otherwise note d . ( ' ! . E B . . !. Jan. 27. 198 1 , as amended at - - . E B . . . f Jan. 5 , 1999; . . . E B . . ?,; Q . . f Apr. 24 , 2001] † 5 6 . 1 02 Definit i on s . As used i n th i s part: (a) A ct means the Federal Food, Dru g , and Cosmet ic Act, as amended ( secs. 201 - 90 2 , 52 Stat. 1040 et seq . , as amended ( ? . J . . . . : . : . : .. ? . . . ? . . ? . )). (b) Application for research or marketing permit i nc l udes: (1) A co l or add i tive pet i t i o n , descr i bed i n part 7 1 . (2) Data and i nformat i on regard i ng a substance subm i tted as part of the procedures for establish i ng that a substance i s generally recogn i zed as safe for a use wh ich resu l ts or may reasonab ly be expected to result, d i rect l y or i nd i rect l y , i n i ts becom i ng a component or otherw i se affect in g the characterist i cs of any foo d , descr i bed i n † J . ? 9 : . ? · (3) A food add i t i ve pet i t i o n , descr i bed i n part 1 7 1 . (4) Data and i nformat i on regard i ng a food add i t i ve subm i tted as part of the procedures regardi ng food add i t i ves perm i tted to be used on an i nter i m bas i s pend i ng addit i onal stud y , descr i bed i n . † J .. Q:.J . . - (5) Data and i nformat i on regard i ng a substance subm i tted as part of the procedures for establish i ng a to l erance for unavo i dab l e contam i nants i n food and food - packagi ng mater i a l s , descr i bed i n sect i on 406 of the act. (6) An i nvest i gat i onal new drug applicat i o n , descr i bed i n P. .. . J . ? . . . qf . . ! . .. - . P. ! . · ( 7 ) A new drug applicat i o n , descr i bed i n part 31 4 . ( 8 ) Data and i nformat i on regard i ng the b i oava i l abil i ty or b i oequ i val ence of drugs for human use submitted as part of the proce d ures for i ssu i n g , amend in g , or repea l i ng a b i oequiva l ence requi rement, descr i bed i n part 320.

21CFR5 6 . 1 02( c) ( enhanced display) page3of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 56 . 1 02(b)( 9 ) ( 9 ) Data and i nformat i on regard i ng an over - the - co u nter drug for human use s u b m i tted as part of the procedures for c l ass i fyi ng s u ch drugs as generally recogn i zed as safe and effective and not m i sbrande d , descr i bed i n part 330. ( 1 O ) An app l i cat i on for a b i o l og i cs l icens e , descr i bed i n P . r. ! . . Q . 1 . .2f . . . . i . . . 2 b . .P . ! . - (11) Data and i nformat i on regard i ng a b i o l og i cal product subm i tted as part of the procedures for determ i n i ng that licensed b i o l og i cal products are safe and effect i ve and not m i sbranded , as descr i bed i n P . r . ! . . 9 . 1 . .. U . . ! . 2 b . . P . . t · (12) An Application for an l nvest i gational Dev i ce Exempt i on, descr i bed i n part 812. (13) Data and i nformat i on regard i ng a med i cal devi ce for hu man use subm i tted as part of the procedures for c l ass i fy i ng such devi ces, descr i bed i n part 860. (14) Data and i nformat i on regard i ng a med i cal devi ce for hu man use subm i tted as part of the procedures for estab l i sh i n g , amend i n g , or repealing a standard for such devi c e , descr i bed i n part 8 6 1 . (15) An app l i cat i on for premarket approval of a med i cal dev i ce for human us e , descr i bed i n sect i on 515 of the act. (16) A prod u ct devel opment protocol for a med i cal dev i ce for human us e , descr i bed i n sect i on 515 of the act. (17) Data and i nformat i on regard i ng an e l ectron i c product subm i tted as part of the procedures for establish i n g , amend i n g , or repealing a standard for such products, descr i bed in section 358 of the Pub l i c Hea l th Serv i ce Act. (18) Data and i nformat i on regard i ng an e l ectron i c product subm i tted as part of the procedures for obta i n i ng a vari a n ce from any e l ectron i c prod u ct performance standar d , as descr i bed i n † .. . 1. Q . 1 . Q : . · (19) Data and i nformat i on regard i ng an e l ectron i c product subm i tted as part of the procedures for grant i n g , amend in g , or extend i ng an exempt i on from a rad i at i on safety performance standard, as descr i bed i n . † . J . 9 . 1 . 9 : . † . · (20) Data and i nformat i on regard i ng an e l ectron i c product subm i tted as part of the procedures for obta i n i ng an exempt i on from notificati on of a rad i at i on safety defect or fai l ure of comp l i a n ce w i th a rad i at i on safety performance standar d , descr i bed i n subpart D of part 1003. (21) Data and i nformat i on about a cl i n i cal study of an i nfant formu l a when subm i tted as part of an i nfant for m u l a not i ficat i on under sect i on 4 12(c) of the Federal Foo d , Drug, and Cosmet i c Act. (22) Data and i nformat i on submitted i n a pet i t i on for a n utr i ent content cla i m , descr i bed i n . † . . 1 . 9 . . : . † . . gf ! . . ! .. . 9. . l? . ! E · and for a hea l th c l a i m , descr i bed i n † .. . 1 . Q. 1 . : .?.. Q . . gf.. . . ! . g . .P . ! . · (23) Data and i nformat i on from i nvest i gat i ons i nvolv i ng children subm i tted i n a new d ietary i ngred i ent not i ficat i on, descr i bed i n . † J . 9 : . † . f.. ! . ! . . b . .P. . . . - ( c ) Clinical investigation means any experiment that i nvo l ves a test art i c l e and one or more human subjects, and that e i ther must meet the requ i rements for pr i or subm i ss ion to the Food and Drug Adm i nistrat i on under sect i on 505 ( i ) or 520( g ) of the act, or need not meet the requ i rements for pr i or subm i ss ion to the Food and Drug Adm i nistrat i on u nder these sect i ons of the act, but the resu l ts of wh i ch are i ntended to be l ater subm i tted t o , or he l d for i nspecti on b y , the Food and Drug Adm i nistrat i on as part of an app l i cat i on

21CFR5 6 . 1 02( m ) ( enha n ced display) pa g e4of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 5 6 . 1 02(d) for a research or market ing perm i t. The term does not i nc l ude exper i ments that must meet the provis i ons of part 5 8 , regard i ng nonc l i n i cal l aboratory stud i es. The terms researc h , clinical research, clinical study, study, and clinical investigation are deemed to be synonymous for purposes of this part. (d) Em e rgency u se means the use of a test art i c l e on a human subject i n a l i fe - threateni ng s i tuat i on i n wh i ch no standard acceptab l e treatment i s availab l e , and i n wh i ch there i s not suffic i ent time to obta i n I RB approval. (e) Human subject means an i nd i v i dual who i s or becomes a part i c i pant i n researc h , e i ther as a rec i p i ent of the test art i c l e or as a control. A subject may be e i ther a hea l thy i nd i v i dual or a pat i ent. ( f) Institution means any pub l ic or pr i vate ent i ty or agency ( incl ud i ng Federa l , Stat e , and other agencie s ) . The term facility as used i n sect i on 520 ( g ) of the act i s deemed to be synonymous w i th the term institution for purposes of this part . (g) Institutional Review Board ( IRB ) means any boar d , comm i tte e , or other group formally des i gnated by an i nst i tut i on to rev i e w , to approve the i n i t i at i on of, and to conduct per i od i c review of, b i omed i cal research i nvolv i ng human subject s . The pr i mary purpose of such rev i ew is to assure the protect i on of the r i ghts and welfare of the human subjects. The term has the same mean i ng as the phrase institutional review committee as used i n sect i on 5 2 0 ( g ) of the act. (h) Investigator means an i nd i v i dual who actual l y conducts a clin i cal i nvest i gat i on ( i . e. , under whose i mmed i ate d i rect ion the test art i c l e is adm i nistered or dispensed t o , or used i nvo l v i n g , a subject ) o r , i n the event of an i nvest i gat i on conducted by a team of i nd i v i dua l s, i s the respons i b l e l eader of that team. (i) Minimal risk means that the probabil i ty and magn i tude of harm or d i scomfort ant i c i pated i n the research are not greater i n and of themse l ves than those ord i nar i l y encountered i n da i l y l ife or during the performance of routi ne phys i cal or psycho l og i cal exam i nat i ons or tests. G) Sponsor means a person or other entity that i n i t i ates a c l i n i cal i nvestigati o n , but that does not actually conduct the i nvest i gation, i.e . , the test art i c l e i s adm i n i stered or d i spensed to, or used i nvolv i n g , a subject under the i mmed i ate d i rect i on of another i ndiv i dual. A person other than an i nd i v i dual ( e . g . , a corporat i on or agency) that uses one or more o f i ts own emp l oyees to conduct an i nvest i gation that i t has i n i t i ated is consi dered to be a sponsor (not a sponsor - i nvestigator ) , and the emp loyees are cons i dered to be i nvest i gators. (k) Sponsor - investigator means an i nd i v i dual who both i n i t i ates and actually conduct s , a l one or w i th others, a clin i cal i nvest i gat i o n , i.e . , under whose i mmed i ate d i rect i on the test art i c l e i s adm i nistered or dispensed t o , or used i nvo l v i n g , a subject. The term does not i nc l ude any person other than an i nd i v i dua l , e . g . , i t does not i nc l ude a corporation or agency. The obligat i ons of a sponsor - i nvest i gator under th i s part i nc l ude both those of a sponsor and those of an i nvest i gator. (I) T e st article means any drug for human us e , b i o l o g i cal product for human us e , med i cal dev i ce for human use, human food add i t i v e , co l or add i tiv e , e l ectron i c product, or any other art i cle subject to regu l at i on under the act or under sect i ons 351 or 354 - 360F of the Publ i c Hea l th Serv i ce Act. ( m ) IRB approval means the determ i nat i on of the I RB that the cl i n i cal i nvestigati on has been reviewed and may be conducted at an i nst i tuti on w i t h i n the constra i nts set forth by the I RB and by other i nst i tuti onal and Federal requi rements . ' 1 . .E. . . ! Jan. 27, 1981, as amended at . 1..E . ! i . . Q ? . ! ! ! Mar. 3, 1989; † . ..E.. . . ? . . Q ? . ! June 1 8 , 199 1 ; ¥. : . .E.. . ? . . ! Jan. 199 9 ; ¥. : . . E! . i . ! Oct. 20, 199 9 ; . . .E.. . ? . :!..9 . ? ! . Aug. 29, 2000; . . . . E . ! i . ? 9 . . . ! Apr. 24, 2001; ? 1..E . ! i . ? . ? . ! ! ! Jan. 15 , 2009]

21CFR5 6 . 1 0 5 ( enha n ced display ) pa g e5of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 56 . 1 03 † 5 6 . 1 0 3 Circumstanc e s in which IRB review i s required (a) Except as prov i ded i n † . † . . ? . . :. 1 .Q4. and . ? . . :. 1 . Q † . , any c li n i cal i nvest i gat i on wh i ch m ust meet the requ i rements for pr i or subm i ss i on (as requ ired i n parts 31 2 , 81 2 , and 813) to the Food and Drug Admi n i strati on shall not be i nit i ated un l ess that i nvest i gat i on has been rev i ewed and approved b y , and rema i ns subject to co n t i nu i ng rev i ew b y , an I RB meeting the requ i reme n ts of th i s part. (b) Except as prov i ded i n † . † .. . ? . . . : . .94 . and . ? . . : . 1 . Q † . . the F ood and Drug Adm i n i strat i on may dec i de not to cons i der i n support of an applicat i on for a research or market i ng perm i t a n y data or i nformat i on that has been der i ved from a c l i n i cal i nvest i gat i on that has not been approved b y , and that was not subject to i n i t i al and conti nu i ng rev i ew b y , an I RB meeti ng the requ i reme n ts of th i s part. The deter m i nat i on that a clin i cal i nvest i gat i on may not be cons idered i n support of an applicat i on for a research or market ing perm i t does no t , howeve r , rel i eve the applicant for such a perm i t of any obligat i on under a n y other applicab l e regu l at i ons to subm i t the resu l ts of the i nvest i gat i on to the Food and Drug Adm i n i strat i o n . (c) Compl i ance w i th these regul at i ons will i n no way render i napp l i cab l e perti nent Federal, Stat e , or l ocal l aws or regu l at i ons. £ 1 . . E B . . ! Jan. 27. 198 1 ; 4 . F. . !J. }. 1: 9 ! Feb. 27. 1981} † 5 6 . 1 04 Exempt i ons from IR B requirement. The follow i ng categor i es of cl i n i cal i nvest i gat i ons are exem p t from the requ i reme n ts of th i s part for I RB rev i ew: (a) A n y i nvest i gat i on wh i ch commenced before Ju l y 2 7 , 1 981 and was subject to requ i reme n ts for I RB rev i ew under FDA regu l ations before that dat e , prov i ded that the i nvest i gat i on rema i ns subject to rev i ew of an I RB wh i ch meets the FDA requ i reme n ts i n effect before Ju l y 2 7 , 1981. (b) A n y i nvest i gat i on commenced before J u l y 2 7 , 1 981 and was not otherw i se subject to requ i rements for I RB rev i ew under Food and Drug Admi n i stration regu l at i ons before that date. (c) Emergency use of a test art i c l e , prov i ded that such emergency use i s reported to the I RB w i th i n 5 work i ng days. Any subsequen t use of the test art i c l e at the i nst i tut i on i s subject to I RB rev i e w . (d) Taste and food q u a l i ty eva luat i ons and consumer acce p tance st u d i es, i f who l esome foods w i thout add i t i ves are consumed or i f a food i s consumed that co n ta i ns a food i ngred i ent at or be l ow the l evel and for a use found to be saf e , or agr i cu l tura l , chem i ca l , or environmental contam i nant at or be l ow the l evel found to be saf e , b y the Food and Drug Adm i nistrat i on or approved b y the Envi ronmental Protect i on Agency or the Food Safety and I nspect i on Serv i ce of the U . S. Department of Agr i cu l ture. £ 1 . . E . ! i . . ! Jan. 27. 1981, as amended at - ..E . !J . . ? . . Q ? . t June 1 8 , 1991} † 5 6 . 1 0 5 W a i ver of IR B requirement. On the applicat i on of a sponsor or sponsor - i nvest i gato r , the Food and Drug Adm i n i strat i on may waive any of the requ i reme n ts conta i ned i n these regu l at i on s , i nc l ud i ng the requ i rements for I RB rev i e w , for spec i fic research activ i t i es or for c l asses of research act i v i t i e s , otherw i se covered by these regul at i ons. S ubpart B - Organization and Personnel

21CFR5 6 . 1 06( e ) ( enha n ced display ) pa g e6of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 56 . 1 06 † 5 6 . 1 06 Registrat i on. (a) Who m u st register? Each I RB i n the Un i ted States that rev i ews c li n i cal i nvest i gat i ons regu l ated by FDA under sect i ons 505{i ) or 520( g ) of the act and each IRB i n the Un i ted States that rev i ews clin i cal i nvest i gat i ons that are i ntended to support app l i cat i ons for research or market i ng perm i ts for FDA regu l ated products m ust reg i ster at a s i te ma i ntai ned by the Department of Hea l th and Human Servi ces ( HHS ) . ( A research perm i t under sect i on 505(i ) of the act i s usually known as an i nvest i gat i onal new drug app l i cat i on ( I ND ) , while a research perm i t under sect i on 520 ( g ) of the act is usually known as an i nvest i gat i onal devi ce exempt i on ( IDE ) . ) An i ndiv i dual author i zed to act on the I RB ' s beha l f must subm i t the registrat i on i nformat i on. All other I RBs may reg i ster vo l untar i l y . (b) What information m u st an IRB register? Each I RB must prov i de the follow i ng i nformat i o n : (1) The name, ma i l i ng addres s , and street address ( if d i fferent from the mailing address) of the i nst i tut i on operat i ng the I RB and the nam e , mailing addres s , phone numbe r , facs i m i l e nu m be r , and e l ectron i c mail address of the seni or officer of that i nst i tuti on who i s respons i b l e for oversee i ng act i v i t i es performed b y the I RB; (2) The I RB's nam e , mailing ad d res s , street address ( i f different from the mailing addres s ) , phone n u mbe r , facs i mile nu m be r , and e lectron i c mail address; each I RB cha i rperson's nam e , phone numbe r , and e l ectron i c ma i l addres s ; and the nam e , ma i l i ng addres s , phone numbe r , facs i m i l e numbe r , and e l ectron i c mail address of the contact person prov i d i ng the regi strat i on i nformat i o n . (3) The approx i mate number of act i ve protoco l s i nvo l v i ng FDA - regu l ated products rev i ewed. For purposes of th i s ru l e , an Hact i ve protoco l · is any protocol for wh i ch an I RB conducted an i nitial rev i ew or a cont i nu i ng rev i ew at a convened meeti ng or u nder an exped i ted rev i ew procedure dur i ng the preced i ng 12 months; and (4) A descr i pt i on of the types of FDA - regu l ated products (such as b i o l og i cal prod u cts, co l or add i tive s , food add i t i ves, human drug s , or med i cal dev i ce s ) i nvo l ved i n the protoco l s that the I RB rev i ews. (c) Whe n must an IRB register? Each I RB must subm i t an i n i t i al registrat i on. The i n i t i al re g i strat i on must occur before the I RB beg ins to rev i ew a cl i n i cal i nvest i gati on descr i bed i n p r , g . r . P. . . ( ) . of this sect i on. Each I RB must renew i ts registrat i on every 3 year s . I RB reg i strat i on becomes effect i ve after rev i ew and acceptance by HH S . (d) Wh e re can an IRB register? Each I RB may register e l ectroni cally through ! I P ! !.. . ! P . . : . ! ! . : ! . :!. . : 9. Y ( . ' ! 0 !. : I f an I RB l acks the abil i ty to register e l ectron i call y , i t must send i ts regi strat i on i nformat i on, i n wr i tin g , to the Office of Good C l i n i cal Pract i c e , Office of Speci al Med i cal Program s , Food and Drug Adm in i stration, 10903 New Hampsh i re Av e . , B l dg. 3 2 , Rm. 5 1 2 9, S i l ver Spr i n g , MD 2 0993. (e) How does an IRB revise its registration information? I f an I RB's contact or cha i r person i nformat i on change s , the I RB must revise i ts regi stration i nformat i on by subm i tt i ng any changes i n that i nformat i on w i th i n 90 days of the chang e . An I RB's decis i on to rev iew new types of FDA - regu l ated products (such as a decis i on to rev i ew stud i es perta i n i ng to food add i tives whereas the I RB prev i ous l y rev i ewed stud i es perta i n i ng to drug product s ) , or to d i scont i nue rev i ew i ng cli n i cal i nvest i gat i ons regu l ated by FDA i s a change that must be reported w i th i n 30 days of the change. An I RB ' s dec i s i on to d i sband is a change that must be reported w i th i n 30 days of permanent cessat i on of the I RB ' s rev i ew of research . All other i nformat i on changes may be reported when the I RB renews i ts registrat i o n . The rev i sed i nformat i on must be sent to FDA e i ther e l ectron i cally or i n wr i ti ng i n accordance w i th p r . . 9 . E . P . . . J ) . of this sect i on. f? . 1 . .E. !! . . ? . . ! ! t Jan. 15 , 200 9 , as amended at .! . .E . B ..! . 1 . Q . t Mar. 15 , 2013]

21CFR5 6 . 1 0 8 (8) ( 3 ) ( enhan c ed display ) pa g e7of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR5 6 . 1 07 † 5 6 . 1 0 7 IRB membershi p . (a) Each I RB shall have at l east five members, with vary ing backgrounds to promote comp l ete and adequate rev iew of research act i v i t i es common l y conducted by the i nst i tuti on. The IRB shall be suffic i ent l y qualified through the exper i ence and experti se of i ts members, and the d i versity of the members, i nclud i ng consi derat i on of rac e , gende r , cu l tural background s , and sensitivi ty to such i ssues as co m mun i ty att i tudes, to promote respect for i ts adv i ce and counsel in safeguard i n g the r i ghts and we l fare of human subjects. I n add i t i on to possess i ng the profess i onal co m petence necessary to rev i ew the specific research act i v i t i e s , the I RB shall be ab l e to ascerta i n the acceptabili ty of proposed research in terms of i nst i tut i onal comm i tments and regu l at i ons, app l i cab l e l a w , and standards of profess i onal conduct and pract i c e . * * * The IRB shall therefore i nc l ude persons know l edgeab l e i n these areas. I f an I RB regu l ar l y rev i ews research that i nvolves a vul nerab l e category of subject s , such as children , pr i soner s , pregnant wome n , or handicapped or mental l y d isab l ed person s , cons i derat i on shall be g i ven to the i nclus i on of one or more i nd i v i dua l s who are know l edgeab l e about and exper i enced i n work i ng w i th those subject s . (b) Every nond i scr i m i natory effort will be made to ensure that no I RB consists ent i re l y of men or ent i re l y of wome n , i nc l ud i ng the i nst i tuto n ' s cons i derat i on of qualified persons of both sexe s , so l ong as no sel ect i on i s made to the I RB on the bas i s of gender. No I RB may cons i st ent i re l y of me m bers of one profess i o n . (c) Each I RB shall i nc l ude at l east one member whose pr i mary concerns are i n the sc i ent i f i c area and at l east one member whose pr i mary concerns are i n nonsc i ent i fic areas. (d) Each I RB shall i nc l ude at l east one member who i s not otherwise affi l i ated w i th the i nst i tuti on and who i s not part of the i mmed i ate fam i l y of a person who is affiliated w i th the i nst i tut i o n . (e) No I RB may have a member part i c i pate i n the I RB' s i n i t i al or cont i nu i ng rev i ew of any project i n wh i ch the member has a confli ct i ng i nteres t , except to prov i de i nformat i on requested b y the I RB. ( f) An I RB ma y , i n i ts d i scret i on, i nv i te i nd i v i dua l s w i th competence i n spec i al areas to ass i st i n the rev i ew of comp l ex i ssues wh i ch requi re experti se beyond or i n add i t i on to that ava i l ab l e on the I RB. These i ndiv i dua l s may not vote w i th the I RB. f . . . E . - !.. Jan. 27, 198 1 , as amended at - ..E. . . Q f. 1 June 1 8 , 199 1 ; † . . E. . .! . . 1 June 28, 1991; .!. . . E.. . t Q . J . 1 Mar. 15 , 2013] S ubpart C - IRB Functions and Operations † 5 6 . 1 08 IR B funct i ons and operations . I n order to fu l fill the requ i rements of these re g u l at ion s , each I RB shall: (a) Follow wr i tten procedures: (1) For conduct i ng i ts i n i t i al and cont i nu i ng rev i ew of research and for report i ng i ts find i ngs and act i ons to the i nvest i gator and the i nst i tuti o n ; (2) for determ i n i ng wh ich projects requ i re rev i ew more often than annually and wh i ch projects need ver i f i cat i on from sources other than the i nvest i gator that no mater i al changes have occ u rred s i nce prev i ous I RB rev i ew; (3) for ensur i ng prompt report i ng to the IRB of changes i n research act i v i t y ; and

21CFR5 6 . 1 09( e ) ( enha n ced display ) page8of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 5 6 . 1 08 ( a ) ( 4 ) ( 4 ) for ensur i ng that changes i n approved researc h , dur ing the per i od for wh i ch I RB approval has al ready been give n , may not be i n i t i ated w i tho u t I RB rev i ew and approval except where necessary to el i m i nate apparent i mmed i ate hazards to the human subjects. (b) Follow wr i tten procedures for ensuri ng prompt report i ng to the I R B , appropr i ate i nst i t u t i onal offic i a l s , and the Food and Drug Adm i n i strat i on of: (1) Any unant i c i pated prob l ems i nvo l v i ng r i sks to human subjects or others; (2) any i nstance of ser i ous or co n t in u i ng noncompl i ance w i th these regu l at i ons or the requ i rements or determ inat i ons of the I RB; or (3) any suspens ion or ter m i nat i on of I RB approval. (c) Exce p t when an exped i ted rev i ew procedure i s used (see † . . ? . . : 1 . J . . Q ) , rev i ew proposed research at convened meeti ngs at wh i ch a major i ty of the members of the I RB are present, i nc l ud i ng at l east one member whose pr i mary concerns are i n nonscient i fic areas. I n order for the research to be approved, i t shall rece i ve the approval of a major i ty of those members present at the meet i ng. f 1 . .E . f! . . . ! Jan. 27, 1981, as amended at . .E . . ? . ? . . Q ? . t June 18, 199 1 ; .!. . .E. . . † . ? . . Mar. 4, 2002} † 5 6 . 1 0 9 IRB review of researc h . (a) An I RB shall rev i ew and have author i ty to approve, requ i re mod i ficat i ons i n ( to secure approva l ) , or d i sapprove all research activ i t i es covered b y these regu l at i ons. (b) An I RB shall requ i re that i nformat i on g i ven to subjects as part of i nformed consent i s i n accordance w i th † . . . Q : ?.:?. · The I RB may requ i re that i nformat i o n , i n add i tion to that spec i fically me n t i oned i n † . . ?. Q . - . f. : † . , be g i ven to the subjects when i n the I RB's judgment the i nformat i on wou l d mean ingfully add to the protect i on of the r i ghts and we l fare of subjects. (c) An I RB shall requ i re documentation of i nformed consent i n accordance w i th † . . Q . . . ? . :? . . 2 f. . ! . ! . h .P . ! t · exce p t as follows: (1) The I RB ma y , for some or all subjects , wa i ve the requi reme n t that the subjec t , or the subject's l egally a u thor i zed represe n tat i v e , s i gn a wr i tten consent form if i t finds that the research presents no more than m i n i mal r i sk of harm to subjects and i nvolves no procedures for wh i ch wr i tten conse n t i s normally requ i red o u ts i de the research context; or (2) The I RB ma y , for some or all subjects , find that the requ i reme n ts i n † . .. Q . . . ?.: 4 . . 2 f . ! . ! .. h . P . ! . r. for an exception from i nformed conse n t for emergency research are met. (d) I n cases where the documentat i on requ i reme n t i s wa i ved under P . . ! . 9 ! P. b . . .C 9 X J of th i s sect i o n , the I RB may requ i re the i nvest i gator to prov i de subjects w i th a wr i tten stateme n t regard i ng the researc h . (e) An I RB shall notify i nvest igators and the i nst i t u t i on i n wr i t i ng o f i ts deci s i on to approve or d i sapprove the proposed research act i v i t y , or of modificat i ons requ i red to secure I RB approval of the research act i v i ty. I f the I RB dec i des to d i sapprove a research act i v i t y , i t shall i nc l ude i n i ts wr i tten not i ficat i on a statement of the reasons for i ts deci s i on and g i ve the i nvest i gator an opportunity to respond i n person or i n wr i t i ng. F or i nvest i gat i ons i nvo l v i ng an except i on to i nformed conse n t under . † . . . 9 : . ? . . 4 . . f.! . ! . . b . P . . t . an I RB shall prom p t l y notify i n wr i t i n g the i nvest i gator and the sponsor of the research when an I RB determ i nes that i t

21CFR 5 6 . l l O(d.) ( enhanced display ) pa g e9of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 5 6 . 1 0 9 (f) cannot approve the research because i t does not meet the criteri a i n the except i on prov i ded under † . . 9 : ?.4 ( ) . . 5 ? .f.. . ! .. . P. . . or because of other re l evant ethi cal concerns. The wr i tten not i f i cat i on shall i nclude a statement of the reasons for the I RB' s determ i nat i on. ( f) An I RB shall conduct cont i nu i ng rev i ew of research covered b y these re g u l at i ons at i nterva l s appropr i ate to the degree of risk, but not l ess than once per yea r , and shall have author i ty to observe or have a t h i rd party observe the consent process and the research . (g) An I RB shall prov i de i n wr i ting to the sponsor of research i nvo l v i ng an except i on to i nformed consent under † . . ?. 9 : . ?.4 . . . f. . . ! ... . P. . E a copy of i nformat i on that has been public l y disc l osed u nder † . . 9 : . ? . . . ( ) ( ?} . ( ! .! ) . and ( ) . ( !. l . Q . ! . ! l. f. . . ! .. . P ! . - The I RB shall prov i de th i s i nformat i on to the sponsor prompt ly so that the sponsor i s aware that such d i sc l osure has occurred. Upon rece i pt, the sponsor shall prov i de cop i es of the i nformat i on d i sc l osed to FDA. (h) When some or all of the subjects i n a study are children , an I RB must determ i ne that the research study i s i n comp l i ance w i th P . r. ! . . ? . . Q , ... . . f? . . . t ! ? . . . 2 J . . ! .. . 9 . . . f ? ! . . · at the t i me of i ts i n i t i al rev i ew of the research. When some or all of the subjects i n a study that was ongo i ng on Apr i l 30, 2001 , are ch i l dre n , an I RB must conduct a review of the research to determ i ne compliance w i th P . r. ! . . ? . . Q , ... . . P . . . . . !? . . . 2 ! . . . ! .. . . P. . . . e i ther at the t i me of cont i nu i ng rev i ew o r , at the d i scret i on of the I R B , at an earlier dat e . f 1 .E . ! i . . !. Jan. 27, 198 1 , as amended at . . 1.E . ! i .. . ? . . ? . . 1 Oc t . 2, 1996 ; . . . F B . . ? . 9 . . . 1 Apr. 24, 2007; .? . .E . ! i . . ? . ? . . . ? . . ? . 1 Feb. 26, 2013] † 5 6 . 1 1 0 Expedited review procedures fo r certain kinds of re s earc h i n volving no more than minimal risk, and fo r minor chan g e s i n approved re s earch. (a) The Food and Drug Adm in i strat i on has estab l ishe d , and published i n the FEDERAL REG I STER, a l ist of categor i es of research that may be rev i ewed by the I RB through an exped i ted rev i ew procedure. The list will be amended, as appropr i at e , through per i od i c repub l i cat i on i n the FEDERAL REG I STER. (b) An I RB may us e the exped i ted rev i ew procedure to rev i ew e i ther or both of the fol l ow ing: (1) Some or all of the research appear i ng on the l i st and found by the rev i ewer( s ) to i nvolve no more than m i n i mal r i sk, (2) m i nor changes i n prev i ous l y approved research dur i n g the peri od (of 1 year or l es s ) for wh ich approval is author i ze d . Under an expedi ted rev i ew proced u r e , the rev i ew may be carr i ed out by the I RB cha i rperson or by one or more exper i enced rev i ewers des i gnated by the I RB cha i rperson from among the members of the I RB. I n rev i ew i n g the researc h , the rev i ewers may exercise all of the author i t i es of the I RB except that the rev i ewers may not disapprove the research. A research act i v i ty may be d i sapproved on l y after rev i ew i n accordance w i th the nonexped i ted rev i ew procedure set forth i n † . . . ? . † .: J . . 9. . { !?. ) . - (c) Each I RB wh i ch uses an exped i ted rev i ew procedure shall adopt a method for keep i ng all members advi sed of research proposa l s wh i ch have been approved under the procedur e . (d) The Food and Drug Adm in i strat i on may restr i ct, suspend , or term i nate an i nst i tuti o n ' s or I RB' s use of the expedi ted rev i ew procedure when necessary to protect the r i ghts or we l fare of subjects. £ 1 . . E B . . . ! Jan. 27, 7987, as amended at . . . EB . ?. . . Q ?,g June 18, 1991]

research i f i t has not been approved by an I RB. 21CFR 5 6 .11 2 { enhanced display ) page 1 0of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 5 6 . 111 † 5 6 . 1 1 1 Criteria for IRB approval o f re search. (a) I n order to approve research covered b y these regu l at ions the I RB shall determ i ne that all of the follow i ng requ i rements are satisfied: (1) Risk s to s u bjects are m i n i m i zed: (i) By using procedures whi ch are consistent w i th sound research des i g n and wh ich do not unnecessar i l y expose subjects to risk, and (ii) whenever appropr i ate, by us i ng procedures already be i ng performed on the subjects for d i agnost i c or treatment purpose s . (2) Risk s to s u bjects are reasonab l e i n re l at i on to anti c i pated bene f i t s , i f an y , to subject s , and the i mportance of the know l edge that may be expected to resu l t. I n eva l uat i ng r i sks and benef i ts, the I RB shou l d cons i der on l y those risks and benefits that may resu l t from the research (as distin g uished from risks and benefits of therap i es that subjects wou l d rece i ve even i f not part i c i pat i ng i n the research) . The I RB shou l d not cons i der possi b l e l ong - range effects of app l y i ng know l edge ga i ned i n the research ( for example, the poss i b l e effects of the research on public pol i c y ) as among those research r i sks that fall w i th i n the p u rv i ew o f i ts respons i bil i ty . (3) Se l ect i on of subjects is equ i tab l e . I n mak i ng this assessment the I RB shou l d take i nto account the purposes of the research and the sett i ng i n wh i ch the research will be conducted and shou l d be part i cu l ar l y cogn i zant of the speci al prob l ems of research i nvolv i ng vu l nerab l e popu l at i ons, such as ch i l dre n , prisoner s , pregnant wome n , hand i cappe d , or mentally d isab l ed person s , or econom i cally or educat i onally d i sadvantaged person s . (4) I nformed consent will be sought from each prospect i ve subject or the subject ' s l egally authorized representat i v e , i n accordance w i th and to the extent requi red by part 50. (5) I nformed consent will be appropr i ate l y documente d , i n accordance w i th and to the extent requ i red by . † . . ? . 9 : ?.:? . .. (6) Where appropr i at e , the research p l an makes adequate prov i s i on for mon i tor i ng the data collected to ensure the safety of subject s . ( 7 ) Where appropr i at e , there are adequate prov i s i ons to protect the privacy of subjects and to ma i ntai n the confident i ality of data. (b) When some or all of the subject s , such as ch i ldren, pr i soners, pregnant wome n , hand i capped, or mentally d i sab l ed person s , or econom i cal l y or educat i onally disadvantaged persons, are l i ke l y to be vul nerab le to coerc i on or undue i nfluence add i t i onal safeguards have been i nc l uded i n the study to protect the r i ghts and welfare of these subjects. (c) I n order to approve research i n wh i ch some or all of the subjects are children , an I RB must determ i n e that all research is i n comp l i ance w i th P . r. ! .. . Q , ... !:. ' . P . . . . Q . . 2 . . . ! .. 2 . . P . ! . · { 1 . . E B . . !. Jan. 27. 198 1 , as amended at . . .fB . . ?..? . .Q? . g June 1 8 , 7997; † . . . r n . ?..9 . . ? . ? . . , Apr. 2 4 , 2001] † 5 6 . 1 1 2 Review b y institut i on. Research covered by these regul at ions that has been approved by an I RB may be subject to further appropr i ate rev i ew and approval or d i sapproval by offic i a l s of the i nst i tuti on. Howeve r , those offic i a l s may not approve the

pagellof13 21CFR5 6 . ll S ( c ) ( enhanced di s pla y ) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR5 6 . 113 † 5 6 . 1 1 3 Suspension o r termination of IRB approval of research. An I RB shall have author i ty to suspend or term i nate approval of research that i s not be i ng conducted i n accordance w i th the I RB ' s requ i reme n ts or that has been associated w i th unexpected ser i ous harm to subjects. A n y suspens i on or term i nat i on of approval shall i nc l ude a stateme n t of the reasons for the I RB ' s act i on and shall be reported prompt l y to the i nvest i gato r , appropr i ate i nst i t u t i onal officia l s , and the Food and Drug Admi n i stratio n . † 5 6 . 1 1 4 C ooperative re s earch. I n comp l y i ng w i th these regu l at i ons. i nst i t u t i ons i nvo l ved i n mu l t i - i nst i t u t i onal studi es may use jo i nt rev i e w . reliance u pon the rev i ew of another qualified I RB, or s i milar arrangeme n ts a i med at avoi dance of duplicat i on of effort. S ubpart D - Re c ords and Reports † 5 6 . 1 1 5 IRB record s . (a) An i nst i tut i o n , or where appropr i ate an I RB, shall prepare and ma i n ta i n adeq u ate docume n tat i on of I RB act i v i t i e s , i nc l ud i ng the fol l ow i ng: (1) Cop i es of all research proposa l s rev i ewed, sc i e n t i f i c eval uat i on s , if an y , that accompa n y the proposal s , approved samp l e consent documents , progress reports subm i tted by invest i gator s , and reports of i njur i es to subjects. (2) M i n u tes of I RB meetings wh i ch shall be i n suffici e n t deta i l to show attendance at the meet i ng s ; act i ons taken b y the I R B ; the vote on these act i ons i nc l ud i ng the nu m ber of members vot i ng fo r , aga i nst, and absta i n i ng; the bas i s for requ i r i ng changes i n or d i sapprov i ng research; and a wr i tten summary of the d i scuss i on of controverted i ss u es and the i r reso l ut i on. (3) Records of cont inu i ng rev i ew act i v i t i es. (4) Cop i es of all correspondence between the I RB and the i nvest i gators. (5) A list of I RB members i de n t i f i ed by nam e ; earned degrees; representati ve capac i ty; i nd i cat i ons of exper i ence such as board certificat i ons, license s , etc . , suffici ent to descr i be each member ' s ch i ef a n t i c i pated co n tr i but i ons to I RB de l i berat i ons; and a n y emp l oyment or other re l at i onsh i p between each member and the i nst i t u t i o n ; for examp l e: ful l - t i me empl oyee, part - t i me emp l oyee, a member of govern i ng panel or boar d , stockho l de r , pa i d or unpa i d consu l ta n t. (6) Wr i tten procedures for the I RB as requ i red by . † . . ? . . : J . . Q . . . C ) and. { ) . ( 7 ) Stateme n ts of s i gn i ficant new find i ngs prov i ded to s u bject s , as requ i red b y † . . ? . 9 : . ? : (b) The records requ ired b y th i s regu l at i on shall be reta i ned for at l east 3 years after comp l et i on of the researc h , and the records shall be access i b l e for i nspect i on and copy i ng by author i zed represe n tatives of the Food and Drug Adm i n i strat i on at reasonab l e t i mes and i n a reasonab l e manne r . (c) The Food and Drug Admi n i strati on may refuse to cons i der a cl i n i cal i nvest i gat i on i n support of an app l i cat i on for a research or market i ng perm i t if the i nst i tut i on or the I RB that rev i ewed the i nvest i gat i on refuses to allow an i nspect i on under t h i s sect i on. £ 1 . . E B . !J . ?. Jan. 27, 198 1 , as amended at - ..f. _ ?..f ! . . 9. . ? . . ! June 1 8 , 199 1 ; † 7...f. . . . † . f! . _ ? ! . Mar. 4, 2002} S ubpart E - Administrat i ve A ctions for Nonc omplian c e

21CFR5 6 . 1 2 1 ( c ) ( enhanced dis p lay) page12of13 Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 21CFR 5 6 . 120 † 5 6 . 1 2 0 L e sser administrative action s . (a) I f apparent nonco m pliance w i th these regu l at i ons i n the operati on of an I RB i s observed b y an FDA i nvest i gator dur i ng an i nspect i o n , the i nspector will present an oral or wr i tten summary of observat i ons to an appropr i ate represe n tative of the I RB. The Food and Drug Ad m i n i strat i on may subsequen tly send a l etter descr i b i n g the noncompliance to the I RB and to the parent i nst i t u t i on. The agency will requ i r e that the I RB or the parent i nst i t u t i on respond to th i s l etter w i th i n a t i me per i od specified by FDA and descr i be the correct i ve act i ons that will be taken by the I R B , the i nst i t u t i o n , or both to ach i eve compliance w i th these regu l at i ons. (b) On the bas i s of the I RB ' s or the i nst i t u t ion ' s respons e , FDA may schedu l e a re i nspect i on to confi rm the adequacy of correct i ve act i ons. I n add i t i on, u n til the I RB or the pare n t i nst i tut i on takes appropr i ate corrective act i o n , the Agency may requ i re the I RB to: (1) W i thho l d approval of new stud i es subject to the requ i rements of t h i s part that are conducted at the i nst i tut i on or rev i ewed b y the I R B ; (2) D i rect that no new subjects be added to ongo i ng stud i es subject to th i s part; or (3) T erm i nate ongo i ng studi es subject to th i s part when do i ng so wou l d not endanger the s u bjects. (c) When the apparent noncompliance creates a s i gn i fica n t threat to the r i ghts and we l fare of human subjects , FDA may not i fy re l eva n t State and Federal regu l atory agenc i es and other parti es w i th a d i rect i nterest i n the Agency's act i on of the def i c i enci es i n the operation of the I RB. (d) The pare n t i nst i tut i on i s presumed to be respons i b l e for the operati on of an I R B , and the Food and Drug Admi n i strat i on will ord i narily d i rect any a d m i n i strat i ve act i on under th i s subpart aga i nst the i nst i t u t i o n . Howeve r , depend i ng on the ev i dence of respons i bil i ty for deficienci es, determ i ned dur i n g the i nvest i gat i o n , the Food and Drug Admi n i strati on may restr i ct i ts adm i n i strative act i ons to the I RB or to a compone n t of the pare n t i nst i t u t ion determ i ned to be respons i b l e for formal des i gnat i on of the I RB. f . . . f. . !i . . ! Jan. 27. 198 1 , as amended at J .. . f. . !i..! . . Q ? . . 1 Apr. 4, 2016] † 5 6 . 1 2 1 Disqualif i cation of an IRB or an inst i tution. (a) Whenever the I RB or the i nst i t u t ion has fai l ed to take adequate steps to correct the noncompliance stated i n the l etter sent b y the agency under † ... f?. J . ? . . Q . ( ) .. and the Comm i ssioner of Food and Drugs determ ines that th i s noncompliance may just i fy the d i squa l i fication of the I RB or of the parent i nst i t u t io n , the Comm i ss i oner will i nst i tute proceed i ngs i n accordance w i th the requ i rements for a regu l atory hear i ng set forth i n part 1 6. (b) The Comm i ss ioner may d i sq u alify an I RB or the pare n t i nst i tut i on i f the Comm i ss i oner determ i nes that: ( 1 ) The I RB has refused or repeated l y failed to comp l y w i th any of the regu l ations set forth i n th i s par t , and ( 2 ) The noncomp l i ance adverse l y affects the r i g h ts or welfare of the human subjects i n a c l i n i cal i nvest i gat i o n . (c) I f the Comm i ss i oner deter m i nes that d i squalificati on i s appropri at e , the Comm i ss ioner will i ssue an order that exp l a i ns the bas i s for the determ i nat i on and that prescr i bes any act i ons to be taken w i th regard to ongoi ng cl i n i cal research conducted under the rev i ew of the I RB. The Food and Drug Adm i n i stration will

page13of13 21CFR5 6 . 12 4 ( enha n ced display) Docus i gn Enve l ope I D: 588FFC7A - 151D - 447B - B8D1 - B848987D 1 C68 21CFR P art56 \ u p to da te as or 9/25/2025 1 In s t i tutional Review Boards 2 1 CFR 56J2 1 (d) send not i ce of the d i squa l ificat i on to the IRB and the parent i nst i tut i o n . Other part i es w i th a d i rect i nterest, such as sponsors and cl i n i cal i nvesti gators, may a l so be sent a not i ce of the disqua l i ficat i on. I n add i t i on, the agency may e l ect to publ i sh a not i ce of i ts act i on i n the FEDERAL REG I ST E R. ( d ) The Food and Drug Adm in i strat i on will not approve an app l i cat i on for a research perm i t for a c l i n i cal i nvest i gat i on that i s to be under the rev i ew of a d i squalified I RB or that i s to be conducted at a d i squali f i ed i nst i tut i o n , and i t may refuse to cons i der i n support of a market i ng perm i t the data from a clin i cal i nvest i gat i on that was rev i ewed by a d isqualified I RB as conducted at a disqual i fied i nst i tuti o n , un l ess the I RB or the parent i nst i tuti on i s re i nstated as prov i ded i n † . . ? . † . : 1 . ? . .. † 5 6 . 12 2 Publ i c disc l osure of information re g arding revocat i on. A determ i nat i on that the Food and Drug Adm i n i strat i on has disqual i fied an i nst i tut i on and the adm i n i strat i ve record regard i ng that determ i nat i on are d i sc l osab l e to the pub l i c under part 2 0 . † 5 6 . 1 2 3 Reinstatement of an IRB or an institution. An I RB or an i nst i tuti on may be re i nstated if the Comm i ss i oner deter m i nes, upon an eva l uat i on of a wri tten subm i ss ion from the I RB or i nstitut i on that exp l a i ns the correct i ve act i on that the i nstitut i on or I RB p l ans to tak e , that the I RB or i nst i tut i on has prov i ded adequate assura n ce that i t will operate i n comp l i ance w i th the standards set forth i n this part. Not i ficat i on of re i nstatement shall be prov ided to all persons not i fied under † .. . ?. † . : . . ? . . H2 ) : † 5 6 . 12 4 Act i ons alternative or addit i onal to disqualifi c ation. D i squa l ificat i on of an I RB or of an i nst i tut i on is i ndependent of, and ne i ther i n lieu of nor a precond i t i on to, other proceed i ngs or act i ons author i zed by the act. The Food and Drug Adm i nistrat i on ma y , at any t i m e , through the Department of Just i ce i nst i tute any appropr i at e jud i c i al proceed i ngs (c i v i l or cr i m i nal) and any other appropr i ate regul atory act i o n , i n add i t i on to or i n l i eu of, and befor e , at the t i me of, or afte r , disqualificat i o n . The agency may a l so refer perti nent matters to another Federal, Stat e , or l ocal government agency for any act i on that that agency determ i nes to be appropr i ate.