L E ADI NG RE GE NE RAT I VE ME DI CI NE Ste m Ce lls - PowerPoint PPT Presentation

L E ADI NG RE GE NE RAT I VE ME DI CI NE Ste m Ce lls USA & Re ge ne r ative Bo sto n, MA Bo sto n, MA 20 Se pte mb e r 2012 20 Se pte mb e r 2012 Me dic ine Congr e ss

Cautionary Statement Concerning Forward ‐ Looking Statements This presentation is intended to present a summary of ACT’s (“ACT”, or “Advanced Cell Technology Inc”, or “the Company”) salient business characteristics. The information herein contains “forward ‐ looking statements” as defined under the federal securities laws. Actual results could vary materially. Factors that could cause actual results to vary materially are described in our filings with the Securities and Exchange Commission. You should pay particular attention to the “risk factors” contained in documents we file from time to time with the Securities and Exchange Commission. The risks identified therein, as well as others not identified by the Company, could cause the Company’s actual results to differ materially from those expressed in any forward ‐ looking statements. Ropes Gray 2

Multiple Plur ipote nt Ce ll Platfor ms Single Blastome r e -de r ive d E mbr yonic Ste m Ce ll L ine s Ge ne ra ting hE SC line s WIT HOUTDE ST RUCT ION OF E MBRYO Utilize s a oduc t De finition : hE SC-de rive d F inal Pr SINGL E CE L L BIOPSY pro duc ts will b e ma nufa c ture d using a c e ll line ma de in 2005 fro m sing le c e ll iso la te d witho ut the de struc tio n o f a ny e mb ryo s Induc e d Plur ipote nc y Ste m Ce lls (iPS) • E a rly I nno va to r in Pluripo te nc y (b e fo re iPS wa s e ve n a te rm!) • Co ntro lling F iling s (e a rlie st prio rity da te ) to use o f OCT 4 fo r induc ing pluripo te nc y 3

am ogr Clinic al Pr RPE

L ife Suppor t to Photor e c e ptor s retina Rod outer segments Cone outer segments RPE Bruch’s membrane Choroidal vessels 5

L ife Suppor t to Photor e c e ptor s ovide s c ritic a l nutrie nts, g ro wth Pr fa c to rs, io ns a nd wa te r pho to re c e pto rs se e no b lo o d • Re c yc le s Vita min A ma inta ins pho to re c e pto r • e xc ita b ility Rod outer segments Cone outer segments F unc tion of RPE L aye r De toxifie s pho to re c e pto r la ye r RPE Maintains Bruc h’ s Me mb ra ne Bruch’s membrane Choroidal vessels • na tura l a ntia ng io g e nic b a rrie r immune privile g e o f re tina • bs stra y lig ht / pro te c ts fro m UV Absor 6

L ife Suppor t to Photor e c e ptor s Dry AMD We t AMD L oss of RPE c e lls Br uc h’s Me m. de hisc e nc e Build up of toxic waste Chor oidal ne ovasc ular ization L oss of photor e c e ptor s 7

RPE T he r apy- Rationale • E asy to ide ntify – a ids ma nufa c turing • Small dosage size – le ss tha n 200K c e lls • Immune - pr ivile ge d site - minima l/ no immuno suppre ssio n • E ase of administr ation - no se pa ra te de vic e a ppro va l RPE c e ll the r apy may impac t ove r 200 r e tinal dise ase s 8

RPE T he r apy- Rationale ACT ’s RPE Ce ll T he r apy should addr e ss U.S. Patient Population the full r ange of dr y AMD patie nts. • Halt pro gre ssio n o f visio n lo ss in e arly Early Stage AMD stage patie nts (10-15M) • Re sto re so me visual ac uity in late r stage patie nts Dry AMD re pre se nts mo re tha n 90 c e nt o f a ll c a se s o f AMD pe r Intermediate AMD (5-8M) No rth Ame ric a a nd E uro pe a lo ne ha ve mo re tha n 30 Million dry AMD pa tie nts Late Stage AMD who sho uld b e e lig ib le fo r o ur RPE c e ll (1.75M) the ra py. 9

GMP Manufac tur ing oc e ss fo r diffe re ntia tio n a nd purific a tio n o f RPE • GMP pr – Virtua lly unlimite d supply fro m ste m c e ll so urc e – Optimize d fo r ma nufa c turing Pro duc t Co ld Cha in is E a sily Sc a le d fo r Glo b a l Sa le s Ide al Ce ll T he r apy Pr oduc t – Ce ntra lize d Ma nufa c turing Sma ll Do se s – E a sily F ro ze n a nd Shippe d – Simple Ha ndling b y Do c to r – 10

Char ac te r izing Clinic al RPE L ots • RPE c e lls a re de rive d fro m a n e xte nsive ly te ste d hE S MCB. E ntire pro c e ss is a spe tic ; no a ntib io tic s use d (~110 da ys). • • Cryo pre se rve d b ulk pro duc t is e xte nsive ly te ste d prio r to re le a se . • Bulk pro duc t is tha we d a nd fo rmula te d fo r the ra pe utic o n the da y o f use . • So me unique q ua lity te sts inc lude : Sc re e ning fo r the a b se nc e o f hE S c e lls (I F A) • In- Pr oc e ss Quality T e sting Asse ssing the e xte nt o f diffe re ntia tio n b y: • • F re q ue nt Mo rpho lo g ic a l • g e ne e xpre ssio n (q -RT -PCR) Asse ssme nts (1-2da ys) Pe rio dic Ste rility T e sting • pro te in de po sitio n (I F A sta ining ) • • Re g ula r K a ryo typing • mo rpho lo g ic a l e va lua tio n • I mmuno histo c he mic a l Sta ining • e xte nt o f pig me nta tio n (me la nin) fo r RPE Ma rke rs po te nc y b y pha g o c yto sis a ssa ys (F ACS) • 11

Char ac te r izing Clinic al RPE L ots Quantitative Pote nc y Assay RPE c e ll po te nc y o f e a c h lo t is a sse sse d b y pha g o c yto sis 4 ° C 37 ° C 12

E ffe c ts of Pigme ntation Quantitative Pigme ntation Assay Use me la nin c o nte nt to de te rmine o ptima l time to ha rve st a nd c ryo pre se rve RPE . 2.00 y = 0.0141x + 0.0007 Absorbance at 475nm 1.50 1.00 0.50 0.00 0 20 40 60 80 100120 µg/mL Melanin 13

Pr e c linic al - E xample s I nje c te d huma n RPE c e lls re pa ir mo no la ye r struc ture in e ye c o ntro l tre a te d pho to re c e pto r la ye r is o nly 0 to 1 c e ll thic k witho ut Pho to re c e pto r tre a tme nt la ye r 14

Phase I - Clinic al T r ial De sign SMD and dr y AMD T r ials appr ove d in U.S., SMD T r ial appr ove d in U.K. 12 Pa tie nts / tria l a sc e nding do sa g e s o f 50K , 100K , 150K a nd 200K c e lls. Re gular Monitor ing - inc luding high de finitio n imaging o f re tina Pa tie nt 1 Pa tie nts 2/ 3 150K Cells 200K Cells 50K Cells 100K Cells DSMB Re vie w DSMB Re vie w 15

Phase I – SMD e ndpoints The transplantation of hESC-derived RPE cells MA09-hRPE will be considered safe and tolerated PRIMARY ENDPOINTS: in the absence of:  Any grade 2 (NCI grading system) or greater adverse event related to the cell product ASSESSMENT OF  Any evidence that the cells are contaminated with an infectious agent SAFETY  Any evidence that the cells show tumorigenic potential Evidence of successful engraftment will consist of:  Structural evidence (OCT, fluorescein angiography, autofluorescense photography, slit-lamp examination with fundus photography) that cells have been implanted in the correct location  Electroretinographic evidence (mfERG) showing enhanced activity in the implant location SECONDARY Evidence of rejection will consist of :  Structural (imaging) evidence that implanted MA09-hRPE cells are no longer in the correct ENDPOINTS location or the presence of vascular leakage.  If enhanced electroretinographic activity is observed after the transplantation, subsequent electroretinographic evidence that activity has returned to pre-transplant conditions may be an indication of graft rejection 16 CONFIDENTIAL

Phase I – Dr y AMD e ndpoints The transplantation of hESC-derived RPE cells MA09-hRPE will be considered safe and tolerated PRIMARY ENDPOINTS: in the absence of:  Any grade 2 (NCI grading system) or greater adverse event related to the cell product ASSESSMENT OF  Any evidence that the cells are contaminated with an infectious agent SAFETY  Any evidence that the cells show tumorigenic potential Evidence of successful engraftment will consist of:  Structural evidence (OCT, fluorescein angiography, autofluorescense photography, slit-lamp examination with fundus photography) that cells have been implanted in the correct location  SECONDARY Electroretinographic evidence (mfERG) showing enhanced activity in the implant location ENDPOINTS Evidence of rejection will consist of :  Structural (imaging) evidence that implanted MA09-hRPE cells are no longer in the correct Additional secondary location or the presence of vascular leakage. endpoints will be  If enhanced electroretinographic activity is observed after the transplantation, subsequent evaluated as exploratory electroretinographic evidence that activity has returned to pre-transplant conditions may be an evaluations for potential indication of graft rejection efficacy endpoints. 17 CONFIDENTIAL

Par tic ipating Clinic al Site s World-leading eye surgeons and retinal • US Clinical Trial Sites clinics participate in clinical trials, DSMB • Jules Stein Eye (UCLA) and Scientific Advisory Board • Wills Eye Institute • Bascom Palmer Eye Institute • Massachusetts Eye and Ear Infirmary • European Clinical Trial Sites • Moorfields Eye Hospital ClinicalTrials.gov • Edinburgh Royal Infirmary US: NCT01345006, NCT01344993 UK: NCTO1469832 18

Sur gic al Ove r vie w e : Pr oc e dur 25 Ga ug e Pa rs Pla na • Vitre c to my • Po ste rio r Vitre o us Se pa ra tio n (PVD I nduc 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 • Air F luid E xc ha ng e 19