L E ADI NG RE GE NE RAT I VE ME DI CI NE 1 ooking State - PowerPoint PPT Presentation

L E ADI NG RE GE NE RAT I VE ME DI CI NE 1

ooking State me nts Cautionar y State me nt Conc e r ning F or war d- L T his pre se ntatio n is inte nde d to pre se nt a summary o f ACT ’ s (“ACT ”, o r “Advanc e d Ce ll T e c hno lo g y I nc ”, o r “the Co mpany”) salie nt b usine ss c harac te ristic s. T he info rmatio n he re in c o ntains “fo rwa rd-lo o king state me nts” as de fine d unde r the fe de ral se c uritie s la ws. Ac tual re sults c o uld vary mate rially. F ac to rs that c o uld c ause ac tual re sults to vary mate rially are de sc rib e d in o ur filing s with the Se c uritie s and E xc hang e Co mmissio n. Yo u sho uld pay partic ular atte ntio n to the “risk fac to rs” c o ntaine d in do c ume nts we file fro m time to time with the Se c uritie s and E xc hang e Co mmissio n. T he risks ide ntifie d the re in, as we ll as o the rs no t ide ntifie d b y the Co mpany, c o uld c ause the Co mpany’ s ac tual re sults to diffe r mate rially fro m tho se e xpre sse d in any fo rward-lo o king state me nts. Ro pe s Gray 2

Se ve r al Ke y Infle c tion Points Pr ovide Ne ar - te r m and L ong- te r m Gr owth Oppor tunitie s ge unme t me dic al ne e ds T hr e e c linic al tr ials aime d at ve r y lar • Dry Ag e re la te d Ma c ula r De g e ne ra tio n a nd Sta rg a rdt’ s Dise a se a ffe c t ne a rly 30 millio n pe o ple in the US a nd E U, e xpe c te d to g ro w b y 50% o ve r ne xt 10 ye a rs ld- c lass c e ll biology c apabilitie s Wor • ACT sc ie ntific te a m c o ntinue s to de ve lo p b e st-in-c la ss, a nd o nly-in-c la ss c e ll line s whic h c re a te se ve ra l pre c linic a l o ppo rtunitie s a c ro ss ma ny dise a se a re a s state Str ong Inte lle c tual Pr ope r ty E • 190 pa te nts file d, 37 issue d whic h pro vide ACT with susta ina b le c o mpe titive a dva nta g e fo r de c a de s to c o me e asse ts Ac tive par tne r ing pr ogr am to mone tize non- c or • ACT ma na g e me nt is de dic a te d to mo ne tizing no n-c o re pre -c linic a l a sse ts a nd c o ntinue s to o ptimize po rtfo lio o f o ppo rtunitie s to fue l future c linic a l pro g ra ms 3

Robust De ve lopme nt Pipe line Pr ovide s Multiple Oppor tunitie s to Comme r c ialize and Par tne r Pre-clinical/ POC – in vitro Animal Studies IND Approved Phase I Phase II Phase III Approval Dry AMD ams F irst Prio rity Ba se d On Curre nt SMD ogr F unding Ophthalmology Pr MMD Pho to - re c e pto rs Adva nc e into Ga ng lio n Pha se I a nd Ne uro ns Pa rtne r Co rne a Po te ntia l Go v’ t F und ing Pla te le ts Ba se d o n POC re sults, Me se nc hymal Ste m Ce lls pursue a ppro pria te fund ing a nd c o lla b o ra tio ns 4

Struc ture of the Re tina T he Re tina the lig ht-se nsitive tissue lining the inne r surfa c e o f the e ye Re tina 5

L ife Support for Photore c e ptors Provide s nutrie nts a nd g ro wth fa c to rs RPE L a ye r ha s • pho to re c e pto rs se e no b lo o d multiple c r itic al r ole s Re c yc le s Vita min A in the • ma inta ins pho to re c e pto r e xc ita b ility he alth and De toxifie s pho to re c e pto r la ye r func tion o f pho to re c e pto rs a nd Ma inta ins Bruc h’ s Me mb ra ne the re tina a s a who le . • na tura l a ntia ng io g e nic b a rrie r • immune privile g e o f re tina Absorbs stra y lig ht / pro te c ts fro m UV 6

L ife Support for Photore c e ptors F a ilure o f RPE c e lls re sults in ma ny de g e ne ra tive dise a se s Sta rg a rdt’ s dise a se Myo pic Ma c ula r Dystro phy Ag e -re la te d ma c ula r de g e ne ra tio n (AMD) 7

xpone ntially with Age Pr e vale nc e of AMD Inc r e ase s E E xpo ne ntia l rise in pre va le nc e a nd inc ide nc e ra te s with a g e , with pre va le nc e ra te s o f la te AMD q ua drupling pe r de c a de 60% De ve lo pe d Co untrie s % Pre va le nc e (U.S.) 80+ 50% 65-79 L a te AMD 40% 121 105.3 81.9 Inte rme diate AMD 64.8 30% 52.9 37.4 207.4 205.5 202.7 173.4 20% 142.2 133.7 10% 2000 2010 2020 2030 2040 2050 40-49 50-59 60-69 70-79 80+ Ag e “ma c ula r de g e ne ra tio n will so o n ta ke o n a spe c ts o f a n e pide mic ” - fo rme r Dire c to r o f the Na tio na l E ye Institute Dr Ca rl K upfe r Data fro m http:/ / www.ne i.nih.g o v/ e ye data/ and U.S . Ce nsus Bure au Pub lic atio n “65+ in the Unite d State s”, P23-209 8

xpone ntially with Age Pr e vale nc e of AMD Inc r e ase s E E xpo ne ntia l rise in pre va le nc e a nd inc ide nc e ra te s with a g e , with pre va le nc e ra te s o f la te AMD q ua drupling pe r de c a de T he c urre ntly 30 Million Ame ric a n a nd E urope a n AMD pa tie nts a re proje c te d to be c ome 45 Million pa tie nts by 2025 9

RPE T he r apy- Rationale • Ma ssive unme t me dic a l ne e d • Sma ll dosa g e size – le ss tha n 200K c e lls • Immune - privile g e d site – minima l immuno suppre ssio n • E a se of a dministra tion – no se pa ra te de vic e a ppro va l • Unique me a suring a nd obse rva tion e nvironme nt 10

Sur gic al Ove r vie w Proc e dure : • 25 Ga ug e Pa rs Pla na Vitre c to my • Po ste rio r Vitre o us Se pa ra tio n • Sub re tina l hE SC-de rive d RPE c e lls inje c tio n • Ble b Co nfirma tio n • Da y Surg e ry/ Se da tio n o nly 11

Clinic al T r ials be ing le d by Wor ld L e ade r s in Ophthalmology Mass Eye & Ear Infirmary Edinburgh Royal Infirmary Moorfields Jules Stein Eye Wills Eye (UCLA) Hospital Institute Bascom Palmer Eye Institute Wor ld r e nowne d le ade r ship to he lp us navigate the c linic al path and ultimate ly suppor t mar ke t launc h 12

siste nc e of c e lls Phase I T r ials E xc e e ding E xpe c tations – no adve r se e ve nts and pe r • ve nts No Adve r se E • Pe r siste nc e of c e lls • Impac t on Ac uity Re c o rde d func tio na l visua l impro ve me nts in ma jo rity o f pa tie nts. • I nc re a se d le tte rs o n E T DRS Cha rts • Co lo r pe rc e ptio n • Co ntra st • L o w lig ht visio n 13

aging Re sults Ac tive Clinic al Pr ogr ams in AMD and SMD Indic ate E nc our IND 50% Pa tie nt 100% Pa tie nt Appr ove d E nr ollme nt E nr ollme nt 12/16 patie nts tre ate d U.S. – Dr y AMD U.S. – SMD 10/16 patie nts tre ate d U.K. – SMD 8/12 patie nts tre ate d E nro lling – 12 patie nts to tal U.S. – MMD 2 ye a rs sinc e the first pa tie nts we re tre a te d Me asur able Impr ove me nts in Visual Ac uity for Major ity of T r e ate d Patie nts 14

F irst T re a tme nts informe d a more a g g re ssive stra te g y to tre a t “be tte r vision” c ohort, c ould le a d to broa de r la be l a nd/ or e a rlie r a pprova l Ja nua ry 2013: F DA a ppro ve d a dditio na l 4 pa tie nt “b e tte r visio n” c o ho rts in e a c h tria l. F o r Co ho rt 2a – c a n e nro ll pa tie nts with visio n a s g o o d a s 20/ 100 . Co ho rt 1 Co ho rt 2 Co ho rt 3 Co ho rt 4 50K Ce lls 100K Ce lls 150K Ce lls 200K Ce lls Co ho rt 2a 100K Ce lls 15

Se ve ra l Importa nt c linic a l mile stone s 2H 2013, 1H 2014 Pha se I 150K 200K Pa tie nt fo llo w-up Dry AMD Co ho rt 2a & SMD T ria ls 100K Pha se II PII de sig n Pa tie nt T re a tme nt Se p 2013 Ja n 2014 July 2014 Ja n 2015 Pha se I MMD T ria l Pa tie nt T re a tme nt 16

E xpanding Clinic al Pr ogr ams Myo pia c re a te s a hig he r risk o f pe rma ne nt visio n lo ss due to Myopic Ma c ula r De g e ne ra tion (MMD) • Se ve re ne a r-sig hte dne ss c a use s e lo ng a tio n o f the e ye b a ll -- whic h c a n c a use fissure s in RPE la ye r. Januar y 2013 - F DA Appr ove d MMD Phase I/ II study Jule s Ste in E ye I nstitute (UCL A) a nd ACT 17

Inte lle c tual Pr ope r ty – RPE Pr ogr am Dominant Pate nt Position for T r e ating Re tinal De ge ne r ation Br oad Cove r age for Manufac tur ing RPE Ce lls Br oad pr ote c tion of phar mac e utic al pr e par ations • RPE c e ll suspe nsio ns • sc a ffo lde d RPE la ye rs. RPE Ce lls de r ive d fr om othe r plur ipote nt ste m c e lls Vig ila nt filing on improve me nts 18

T he r ape utic Pipe line Re tina l Ne ura l Prog e nitor c e lls & Isola te d Prote c tive F a c tors  Pho to re c e pto r L o ss, Mo dula tio n o f Mülle r Ce lls  Pro te c tio n o f Re tina l Ga ng lio n c e lls (Gla uc o ma ) Corne a l E ndothe lium  Co rne a l Dise a se He ma ng iobla st c e lls  I sc he mic re tino pa thy – dia b e tic re tino pa thy, va sc ula r o c c lusio ns Me se nc hyma l Stroma l Ce lls  Oc ula r - Gla uc o ma , Uve itis, Re tinitis Pig me nto sa  Auto immune Dise a se s  I nfla mma to ry Dise a se s o r diso rde rs 19

B Y PRODUCI NG T HE DE E OF QUAL Y HIGHE ST GRE IT NARY T CS VE T E RI HE RAPE UT I WE I ND T O BE Se pte mb e r 19, 2013 – NT E A L R I N E ADE “ACT F ile s I nve stig a tio na l Ne w Anima l V E RINARY Drug (I NAD) Applic a tio n with F DA to T re a t T E 10 Diffe re nt Dise a se I ndic a tio ns Using R IVE M E DICINE E GE NE RAT Pluripo te nt Ste m Ce lls” 20

ACT Cor por ate Ove r vie w 21