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

Bo sto n, MA 20 Se pte mb e r 2012 Bo sto n, MA 20 Se pte mb e r 2012

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

Ste m Ce lls USA & Re ge ne r ative Me dic ine Congr e ss

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

Cautionary Statement Concerning Forward‐Looking Statements

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

SINGL E CE L L BIOPSY

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 F inal Pr

• duc t De finition: hE

SC-de rive d 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

RPE Clinic al Pr

• gr

am

5

retina

L ife Suppor t to Photor e c e ptor s

Rod outer segments Cone outer segments RPE Bruch’s membrane Choroidal vessels

6

L ife Suppor t to Photor e c e ptor s

De toxifie s pho to re c e pto r la ye r Maintains Bruc h’ s Me mb ra ne

• na tura l a ntia ng io g e nic b a rrie r
• immune privile g e o f re tina

Absor bs stra y lig ht / pro te c ts fro m UV Pr

• vide s c ritic a l nutrie nts, g ro wth

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

F unc tion of RPE L aye r

Rod outer segments Cone outer segments RPE Bruch’s membrane Choroidal vessels

7

L ife Suppor t to Photor e c e ptor s

L

• ss of RPE

c e lls Build up of toxic waste L

• ss of photor

e c e ptor s

Dry AMD

Br uc h’s Me m. de hisc e nc e Chor

• idal ne ovasc ular

ization

We t AMD

• 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

• ve r

200 r e tinal dise ase s

8

RPE T he r apy- Rationale

9

RPE T he r apy- Rationale

Early Stage AMD (10-15M) Intermediate AMD (5-8M) Late Stage AMD (1.75M)

U.S. Patient Population ACT ’s RPE Ce ll T he r apy should addr e ss the full r ange of dr y AMD patie nts.

• Halt pro gre ssio n o f visio n lo ss in e arly

stage patie nts

• 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

pe r c e nt o f a ll c a se s o f AMD

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 who sho uld b e e lig ib le fo r o ur RPE c e ll the ra py.

• GMP pr
• c e ss fo r diffe re ntia tio n a nd purific a tio n o f RPE

– Virtua lly unlimite d supply fro m ste m c e ll so urc e – Optimize d fo r ma nufa c turing

Ide al Ce ll T he r apy Pr

• duc 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

GMP Manufac tur ing

10

Pro duc t Co ld Cha in is E a sily Sc a le d fo r Glo b a l Sa le s

Char ac te r izing Clinic al RPE L

• ts

11

• 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)

• Asse ssing the e xte nt o f diffe re ntia tio n b y:
• g e ne e xpre ssio n (q -RT
• PCR)
• pro te in de po sitio n (I

F A sta ining )

• mo rpho lo g ic a l e va lua tio n
• e xte nt o f pig me nta tio n (me la nin)
• po te nc y b y pha g o c yto sis a ssa ys (F

ACS)

In- Pr

• c e ss Quality T

e sting

• F

re q ue nt Mo rpho lo g ic a l Asse ssme nts (1-2da ys)

• Pe rio dic Ste rility T

e sting

• Re g ula r K

a ryo typing

• I

mmuno histo c he mic a l Sta ining fo r RPE Ma rke rs

Char ac te r izing Clinic al RPE L

• ts

12

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

E ffe c ts of Pigme ntation

13

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 .

y = 0.0141x + 0.0007 0.00 0.50 1.00 1.50 2.00 20 40 60 80 100120 Absorbance at 475nm µg/mL Melanin

Quantitative Pigme ntation Assay

Pr e c linic al - E xample s

14

c o ntro l tre a te d

I nje c te d huma n RPE c e lls re pa ir mo no la ye r struc ture in e ye

Pho to re c e pto r la ye r

pho to re c e pto r la ye r is o nly 0 to 1 c e ll thic k witho ut tre a tme nt

Phase I - Clinic al T r ial De sign

15

SMD and dr y AMD T r ials appr

• ve d in U.S., SMD T

r ial appr

• ve 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

50K Cells 100K Cells 150K Cells 200K Cells

Pa tie nt 1 Pa tie nts 2/ 3 DSMB Re vie w DSMB Re vie w

Phase I – SMD e ndpoints

16

PRIMARY ENDPOINTS: ASSESSMENT OF SAFETY

The transplantation of hESC-derived RPE cells MA09-hRPE will be considered safe and tolerated in the absence of:  Any grade 2 (NCI grading system) or greater adverse event related to the cell product  Any evidence that the cells are contaminated with an infectious agent  Any evidence that the cells show tumorigenic potential

SECONDARY ENDPOINTS

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 Evidence of rejection will consist of:  Structural (imaging) evidence that implanted MA09-hRPE cells are no longer in the correct 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

CONFIDENTIAL

Phase I – Dr y AMD e ndpoints

17

PRIMARY ENDPOINTS: ASSESSMENT OF SAFETY

The transplantation of hESC-derived RPE cells MA09-hRPE will be considered safe and tolerated in the absence of:  Any grade 2 (NCI grading system) or greater adverse event related to the cell product  Any evidence that the cells are contaminated with an infectious agent  Any evidence that the cells show tumorigenic potential

SECONDARY ENDPOINTS

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 Evidence of rejection will consist of:  Structural (imaging) evidence that implanted MA09-hRPE cells are no longer in the correct 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

Additional secondary endpoints will be evaluated as exploratory evaluations for potential efficacy endpoints.

CONFIDENTIAL

Par tic ipating Clinic al Site s

18

World-leading eye surgeons and retinal clinics participate in clinical trials, DSMB and Scientific Advisory Board

• US Clinical Trial Sites
• Jules Stein Eye (UCLA)
• Wills Eye Institute
• Bascom Palmer Eye Institute
• Massachusetts Eye and Ear Infirmary
• European Clinical Trial Sites
• Moorfields Eye Hospital
• Edinburgh Royal Infirmary

ClinicalTrials.gov US: NCT01345006, NCT01344993 UK: NCTO1469832

Sur gic al Ove r vie w

19

Pr

• c e dur

e:

• 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

Pr e liminar y Re sults

20

No Adve r se E ve nts No sig ns o f hype rpro life ra tio n, a b no rma l g ro wth, re je c tio n o r re tina l de ta c hme nt. Pe r siste nc e of c e lls Ana to mic a l e vide nc e o f hE SC-RPE surviva l a nd e ng ra ftme nt. I nc re a se d pig me nta tio n within the b e d

• f the tra nspla nt.

Impac t on Ac uity

Re c o rde d func tio na l visua l impro ve me nts in b o th pa tie nts.

Pr e liminar y Re sults – Initial Patie nts

21

Visual Ac uity Me asur e me nts

• SMD Pa tie nt: BCVA impro ve d fro m ha nd mo tio ns to 20/ 800 a nd

impro ve d fro m 0 to 5 le tte rs o n the E T DRS visua l a c uity c ha rt

• Dry AMD Pa tie nt: Visio n impro ve d in the pa tie nt with dry a g e -

re la te d ma c ula r de g e ne ra tio n (21 E T DRS le tte rs to 28)

One Ye ar F

• llow- up:
• Visua l a c uity g a ins re ma in re la tive ly sta b le fo r b o th pa tie nts
• SMD Pa tie nt c o ntinue s to sho w impro ve me nt.

U.K . SMD01 Pa tie nt (a t 6 mo nth fo llo w-up)

• E

T DRS: I mpro ve d fro m 5 le tte rs to 10 le tte rs

• Sub je c tive : Re po rts sig nific a ntly impro ve d a b ility to re a d te xt o n T

V

Cur r e nt Safe ty Pr

• file – Star

gar dt’s T r ial

22

7 SMD Patie nts T r e ate d (a s o f 7 Se pte mb e r 2012)

3 pa tie nts (50K c e lls c o ho rt) tre a te d a t UCL A – US T ria l 3 pa tie nts (50K c e lls c o ho rt) tre a te d a t Mo o rfie lds E ye – UK T ria l 1 pa tie nt (100K c e lls c o ho rt) tre a te d a t Wills E ye – US T ria l No r e por ts of any adve r se e ve nts or c omplic ations due to c e lls pe r se

• No e vide nc e o f infla mma tio n o r infiltra tio n
• No e vide nc e o f e c to pic tissue fo rma tio n
• No e vide nc e o f re tina l de ta c hme nt

Cur r e nt Safe ty Pr

• file – Dr

y AMD T r ial

23

4 dr y AMD Patie nts T r e ate d (a s o f 7 Se pte mb e r 2012)

3 pa tie nts (50K c e lls c o ho rt) tre a te d a t UCL A – US T ria l 1 pa tie nt (100K c e lls c o ho rt) tre a te d a t Wills E ye – US T ria l No r e por ts of any adve r se e ve nts or c omplic ations due to c e lls pe r se

• No e vide nc e o f infla mma tio n o r infiltra tio n
• No e vide nc e o f e c to pic tissue fo rma tio n
• No e vide nc e o f re tina l de ta c hme nt

Inte lle c tual Pr

• pe r

ty – RPE Pr

• gr

am

• T

r e atme nt - Dominant Pate nt Position for

T r e ating Re tinal De ge ne r ation

• Manufac tur

ing - Br

• ad Cove r

age for Manufac tur ing RPE Ce lls fr

• m hE

SC

• Pr

e par ations - Claims dir

e c te d to phar mac e utic al pr e par ations of RPE Ce lls fr

• m hE

SC, inc luding both c e ll suspe nsions and sc affolde d RPE laye r s.

• Sour

c e s – Issue d pate nts c ove r

RPE Ce lls de r ive d fr

• m othe r

plur ipote nt ste m c e lls (inc luding iPS c e lls)

• Vigilanc e – Re gular

ly F iling on Impr

• ve me nts
• E

xte nd pa te nt life c yc le , with sig nific a nc e to c o mme rc ia liza tio n

• I

nc lude c o mpo sitio n-o f-ma tte r c la ims (c e ll pre pa ra tio ns, pha rma c e utic a l pre pa ra tio ns, e tc .)

24

Pr ic e Justific ation

25

Unme t T he r ape utic Ne e d E ffic ac y Patie nt Pr e vale nc e Phar mac oe c onomic s Patie nt Advoc ac y

Pr ic ing Justific ation

a c ro ss a ll c a te g o rie s

• f c o nside ra tio n

RPE Pr

• gr

am - Inve stme nt T he sis

26

• Imme nse unme t me dic al ne e d
• Small Dose s
• Immunopr

ivile ge d – pe r mits c e ntr al (alloge ne ic ) sour c e of c e lls

• Noninvasive monitor

ing of r e tina Mar ke t pote ntial: Mo re tha n 50 millio n pa tie nts in ma jo r ma rke ts. 1% mar ke t pe ne tr ation may r e pr e se nt $5- 10B mar ke t oppor tunity. Orpha n indic a tio ns a re me a ning ful: E stima ting a 10% ma rke t pe ne tra tio n with re o c c urring tre a tme nts e ve ry 3-5 ye a rs, Sta rg a rdt’ s dise a se c a n b e a $100+ millio n/ ye a r pro duc t.

ACT MSC Pr

• gr

am

Me se nc hymal Ste m Ce lls in T he r apy

28

Me se nc hymal ste m c e lls (MSCs) r e gulate immune r e sponse s pr

• vide the r

ape utic pote ntial for tr e ating autoimmune or inflammator y dise ase s.

• Alloge ne ic - witho ut HL

A ma tc hing .

• Pote ntial
• Auto immune c o nditio ns, suc h a s MS, lupus, a nd Cro hn's/ I

BD.

• I

nfla mma to ry Dise a se s

• T

r ac k Re c or d - Adult-de rive d MSCs a lre a dy in 200+ c linic a l tria ls. An "off-the -she lf" c e llular dr ug r e ady for tr e atme nt of a wide r ange of inflammator y and autoimmune dise ase s.

Adult Me se nc hymal Ste m Ce lls

29

Impac ts on Ce ll Banking

• L

imita tio n o n the numb e r o f do se s tha t c a n b e g e ne ra te d fro m a dult do no rs

• Re q uire s c o nsta ntly c re a ting a nd va lida ting MSC b a nks

fro m ne w do no rs

Impac ts on Pote nc y

• Pa ssa g ing re duc e s immuno mo dula to ry po te nc y o f MSC’ s.

Re plic ative Capac ity - limits adult sour

c e s (bone mar r

• w,

fat, e tc ) for alloge ne ic MSC the r apie s.

Substantial ne e d for be tte r MSC pr

• duc ts

hE SC- and iPS – de r ive d MSC

30

ACT Pr

• pr

ie tar y Pr

• c e ss
• hE

SC-de rive d MSCs c a n b e e xpa nde d to la rg e numb e rs o f c e lls

• Ha ve q ua litie s simila r to fe ta l MSC’ s
• Avo id re plic a tive c a pa c ity pro b le m o f “o ld” a dult MSC’ s

Advantage s for Manufac tur ing

• Use Sing le Ma ste r Ce ll Ba nk
• Simplifie s F

DA/ re g ula to ry pro c e ss

• No ne e d fo r finding do no rs
• L

e ss la b o r-inte nsive

Pr e liminar y Data

31

Animal Mode ls te sting hE SC- de r ive d MSC’s

Sub sta ntia lly de c re a se a nd re ve rse dise a se c o nditio ns in a uto immune mo de ls.

• F

a r mo re po te nt tha n a dult (BM) de rive d MSCs.

• Ha ve lo ng e r dura tio n o f a c tio n c o mpa re d to a dult

(BM) de rive d MSCs.

Pote ntial implic ations of inc r e ase d pote nc y and dur ation…

• Bro ade r utility in range o f dise ase s.
• Re duc e d c e lls pe r do se – impro ve d safe ty pro file .
• L
• nge r duratio n be twe e n inje c tio ns.

Pote ntial applic ations

32

• >100 a uto immune dise a se s
• Multiple Sc le ro sis
• Oste o a rthritis
• Apla stic Ane mia
• Cro hn’ s Dise a se / I

BS

• Chro nic Pa in
• L

imb I sc he mia

• He a rt F

a ilure / MI

• Stro ke
• Gra ft-ve rsus-ho st Dise a se
• Spina l Co rd I

njury

• Pa rkinso n’ s Dise a se
• L

ive r Cirrho sis

• E

mphyse ma / Pulmo na ry Dise a se s

• Wo und he a ling

(ulc e rs/ de c ub itus/ b urns)

• HSC e ng ra ftme nt/ irra dia te d

c a nc e r pa tie nts

• E

ye dise a se s (uve itis, re tina l de g e ne ra tio n, g la uc o ma )

ACT Vasc ular Pr

• gr

am

He mangioblast Pr

• gr

am: Ove r vie w

34

T he He mangioblast c e ll is a multipote nt c e ll, and a c ommon pr e c ur sor to he matopoie tic and e ndothe lial c e lls.

He mangioblast c e lls c an be use d to pr

• duc e all c e ll type s in the

c ir c ulator y and vasc ular syste ms

Ge ne r ation of me gakar yoc tye s/ plate le ts

35

Human ES cells Hemangioblasts Megakaryocyte Pro‐platelets

CD41/vWF/DAPI

Char ac te r ization of Plate le ts

36

hE SC- and iPS- de r ive d plate le ts par tic ipate in c lot for mation and r e tr ac tion

Ne xt Ste ps

37



T e sting hE S/ hiPSC-pla te le ts in vitro

• Mo rpho lo g y
• Bio c he mic a l sta tus
• Physio lo g ic a l re spo nse s



T e sting hE S/ hiPSC-pla te le ts in vivo

• Co lla b o ra tio ns unde rwa y with se ve ra l le a ding g ro ups

(inc luding Ha rva rd Unive rsity, Co lumb ia Unive rsity, a nd Unive rsity o f I llino is Co lle g e o f Me dic ine )

• in vivo c irc ula tio n a nd ha lf-life
• in vivo func tio n

F inanc ial Update – Str

• ng Balanc e She e t

38

• Company e nde d 2012 Q2 with $10 million c ash on hand
• $35 million mor

e available unde r e quity line

• Vir

tually de bt- fr e e

• Re c e ive d shar

e holde r appr

• val for

r e ve r se split

• F

ile d applic ation for NASDAQ uplisting and have initial c omme nts Othe r 2012 Mile sto ne s (so fa r)

• I

RB a ppro va ls fro m Wills E ye I nstitute , Ba sc o m Pa lme r E ye Ho spita l a nd Ma ssa c huse tts E ye & E a r

• I

nitia te d E uro pe ’ s first huma n E SC-de rive d tra nspla nt a t Mo o rfie lds E ye Ho spita l

• Pub lishe d first re po rt o f hE

SC-de rive d c e lls tra nspla nte d into huma ns in to p me dic a l jo urna l, T he L anc e t.

• Co mple te d Do se Co ho rt 1 o f pa tie nts in b o th U.S. tria ls;
• Do se d first SMD a nd dry AMD pa tie nts in 100,000 c e ll c o ho rts – no AE

’ s o b se rve d.

ACT Manage me nt T e am

Highly E xpe r ie nc e d and T ightly Inte gr ate d Manage me nt T e am

Gar y Rabin – Chair man & CE O Dr . Robe r t L anza, M.D. – Chie f Sc ie ntific Offic e r E dmund Mic kunas – Vic e Pr e side nt of Re gulator y Affair s Dr . Ir ina Klimanskaya, Ph.D. – Dir e c tor

• f Ste m Ce ll Biology

Dr . Shi-Jiang (John) L u, Ph.D. – Se nior Dir e c tor

• f Re se ar

c h Dr . Roge r Gay, Ph.D. - Se nior Dir e c tor

• f Manufac tur

ing Kathy Singh - Contr

• lle r

Rita Par ke r – Dir e c tor

• f Ope r

ations Dr . Matthe w Vinc e nt, Ph.D. – Dir e c tor

• f Busine ss De ve lopme nt

Bill Douglass – Dir . of Cor por ate Communic ations & Soc ial Me dia

39

T ha nk yo u F

• r mo re info rma tio n, visit www.a dva nc e dc e ll.c o m