L E ADI NG RE GE NE RAT I VE ME DI CI NE May 2014 pr - - PowerPoint PPT Presentation

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

May 2014

pr e se nte d at:

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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

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Ophthalmology Autoimmune/ Inflammation Drug Delivery

Transplantable Photoreceptor Progenitors Transplantable Ganglion Nerve Progenitors DSEK Corneal Transplant Tissue

Neuroprotective/Neuroregulatory

Biologics Multiple Sclerosis Alzheimer’s Disease Inflammatory Bowel Disease Sepsis Wound Healing Engineered Platelets & MK

• Factor XIII • Wound Healing
• Anti-cancer

Engineered RPE

Robust Clinic al and Pr e c linic al Pr

• gr

ams

Lupus Engineered Photoreceptors Transplantable RPE Cells

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Ophthalmology

Robust Clinic al and Pr e c linic al Pr

• gr

ams

Pre-clinical Development Phase 1 Phase 2 Transplantable Photoreceptor Progenitors Transplantable Ganglion Nerve Progenitors DSEK Corneal Transplant Tissue

Neuroprotective/Neuroregulatory

Biologics Dry Age-Related Macular Degeneration (US) Stargardt’s Macular Dystrophy (US & UK) Myopic Macular Degeneration (US) Dry AMD (US) Projected 2H-2014/1H-2015 SMD (US & UK) Projected 2H-2014

Adva nc e d Ce ll T e c hno lo g y’ s

Re g e ne ra tive Ophtha lmolog y Prog ra ms

fo c us o n pre se rving a nd re pa iring ne uro se nso ry re tina a nd c o rne a func tio n

Engineered RPE

TM

Re tina

Struc ture of the Re tina

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L ife Suppor t to Photor e c e ptor s

Provide s nutrie nts a nd g ro wth fa c to rs

• 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

De toxifie s pho to re c e pto r la ye r Ma inta ins 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

Absorbs stra y lig ht / pro te c ts fro m UV

RPE L a ye r ha s

multiple c r itic al r

• le s

in the

he alth and func tion

• f pho to re c e pto rs a nd

the re tina a s a who le .

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L ife Suppor t to Photor e c e ptor s

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 (SMD) Myo pic Ma c ula r Dystro phy (MMD) Ag e -re la te d ma c ula r de g e ne ra tio n (AMD)

Age - Re late d Mac ular De ge ne r ation will Soon T ake on Aspe c ts of an E pide mic

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

E xpone ntial r ise in pr e vale nc e and inc ide nc e r ate s with age . Pr e vale nc e r ate s of late AMD quadr uple pe r de c ade

40% 30% 20% 10% 50-59 40-49 60-69 70-79 80+ Ag e Inte rme diate AMD L a te AMD % Pre va le nc e (U.S.)

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T he pr

• je c te d numbe r
• f pe o ple wo r

ldwide with age - r e late d mac ular de ge ne r atio n in 2020 is 196 millio n, inc r e asing to 288 millio n in 2040 - Wo ng e t al. L

anc e t January 2014

Dissoc iate d RPE Ce lls c a n b e inje c te d into the sub re tina l

spa c e a nd will re b uild func tio na l RPE mo no la ye r whe re na tive RPE is c o mpro mise d o r lo st.

• Simple Ha ndling
• Optimize d fo r la rg e sc a le a nd c e ntra lize d ma nufa c turing
• Sma ll Do se Size tra nsla te s into ACT

’ s a b ility to ma nufa c ture 50,000-100,000 pe r ye a r in e xisting fa c ilitie s.

T he r ape utic T he sis

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

• RPE

la ye r is surg ic a lly a c c e ssib le -

• le a st inva sive me a ns to lo c a lly de live r c e lls
• Adult RPE

tra nslo c a tio n studie s inc lude d disso c ia te d c e ll fo rma ts

• hE

SC-de rive d RPE suppo rte d b y b o th I n Vitro a nd I n Vivo Studie s a t ACT a nd OHSU

Ce ll T he r apy for RPE , Ac hie vable by a Small Company

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Sma ll dosa g e size

• le ss tha n 200K

c e lls

Re la tive ly 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

• me a sura b le a na to mic a l a nd func tio na l e ndpo ints

Ja n 2013: F DA a ppro ve d a dditio na l 4 sub je c t “b e tte r visio n” c o ho rts in e a c h tria l. F

• r Co ho rt 2a – c a n e nro ll sub je c ts with visio n a s g o o d a s 20/ 100.

Co ho rt 1

50K Ce lls

Co ho rt 2

100K Ce lls

Co ho rt 3

150K Ce lls

Co ho rt 4

200K Ce lls

Co ho rt 2a

100K Ce lls

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

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Initial T r ial De sign is Asc e nding Dosage Safe ty Study 12 Subje c ts – F

• ur

Cohor ts of 3 subje c ts e ac h

Inc lusio n Crite ria BCVA: 20/ 800 o r wo rse Inc lusio n Crite ria BCVA: 20/ 400 o r wo rse Inc lusio n Crite ria BCVA: 20/ 100 o r wo rse Inc lusio n Crite ria BCVA: 20/ 400 o r wo rse Inc lusio n Crite ria BCVA: 20/ 400 o r wo rse

IND Appr

• ve d

50% Pa tie nt E nr

• llme nt

100% Pa tie nt E nr

• llme nt

U.S. – Dr y AMD U.S. – SMD U.K. – SMD U.S. – MMD

12/16 patie nts tre ate d 12/16 patie nts tre ate d 10/12 patie nts tre ate d E nro lling – 12 patie nts to tal

Curre nt Sta tus of P1 T ria ls e na ble s Pla nning for P2

34 Patients Treated to Date

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E a rly Hypo the sis De ve lo pe d fo r PI I , Ve tte d with I nve stig a to rs, Dia lo g ing with MHRA a nd F DA

Jule s Ste in (UCL A) Ma ss E ye & E a r Infirmary Wills E ye Institute Ba sc o m Pa lme r E ye Institute Mo o rfie lds E ye Ho spita l

E dinb urg h Ro ya l I nfirma ry

Clinic al T r ials be ing le d by Wor ld L e ade r s in Ophthalmology

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Wo rld Re no wne d L e a de rship to he lp us na vig a te the Clinic a l Pa th a nd Ultima te ly Suppo rt Ma rke t L a unc h

De live ry of Ce lls Builds on Common Surg e ry

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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

Vitre c to my is the 3rd Mo st F re q ue ntly Pe rfo rme d Ophtha lmic Surg e ry; 1.1m g lo b a lly, 300k in US, pe r ye a r

E la pse d T ime Sinc e T ra nspla nt – a s Ma y 2014

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US Dr y AMD US SMD UK SMD

Inte rim Da ta Ana lysis Inte rim Da ta Ana lysis 2 ye a rs 3 ye a rs 1 ye a r

* US AMD & SMD Co ho rt 2a sub je c ts ra ng e fro m 1-12 mo nths po st-tra nsplant

Cohor t 2a

Ove rvie w of Inte rim Da ta

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Ma nusc ript de ta iling inte rim da ta unde r re vie w a t impa c tful jo urna l Co -autho re d b y partic ipating surg e o ns and c o mpany

• Cle a n sa fe ty pro file
• E

vide nc e o f e ng ra ftme nt a nd pe rsiste nc e o f tra nspla nte d RPE c e lls

• Pe rsisting I

mpro ve me nt o f Visua l Ac uity fo r ma ny pa tie nts

A numb e r o f patie nts with c linic ally sig nific ant impro ve me nts in BCVA AMD-207 impro ve d 20/ 400 to 20/ 40

• Impro ve me nt ha s pe rsiste d thro ug h fo llo w-up visits (> 1 ye a r)

SMD-001 impro ve d fro m HM to 20/ 500

• Impro ve me nt (with furthe r g a ins) ha s pe rsiste d thro ug h fo llo w-up visits (>2 ye a r)

Base d on advic e fr

• m all 5 c linic al tr

ial site s and par tic ipating sur ge ons, as we ll as input fr

• m r

e gulator s, we ar e advanc ing to phase 2 studie s › Ac tive dia lo g with MHRA a nd F DA › Antic ipa te P2 c o mme nc e me nt in 2H2014

E xe mplar s o f Patie nts With Impr

• ve d

Visual Ac uity

E xpanding RPE Pr

• gr

am to Addr e ss an Additional L e ading Cause of Blindne ss

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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.

As the cause of legal blindness, MMD is ranked:

• 7th in the United Sates
• 4th in Hong Kong
• 2nd in mainland China and Japan

Jule s Ste in E ye (UCL A) a nd ACT to I nitia te Pha se I / I I Study

Second Generation RPE Cell Therapy Products

By e ngine e r ing the maste r ste m c e ll bank use d to manufac tur e RPE c e lls, the tr ansplante d RPE c e lls c an e xpr e ss

• Anti- a ng iog e ne ic a g e nts

Re duc e o c c urre nc e o f c ho ro ida l ne o va sc ula riza tio n (we t AMD).

• Comple me nt fa c tor D, F

a c tor C5 a nd/ or F a c tor C3 Inhibitors

Ac tiva tio n o f a lte rna tive c o mple me nt pa thwa y implic a te d in dise a se pro g re ssio n fo r c e rta in pa tie nts

• Anti β- a myloid a g e nts

Druse n de po sits re se mb le a mylo id de po sits.

• Anti- Infla mma tory a g e nts

I L

• 1, I

L

• 2, I

L

• 3, a nd T

NF

• α a nta g o nists

Re c o mb ina nt L ipo c o rtin – a po te nt a nti-infla mma to ry pro te in

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Inte lle c tual Pr

• pe r

ty – RPE Pr

• gr

am

Dominant Pate nt Positions in Major Mar ke ts for Platfor m T e c hnology and T r e atme nts

• Br
• ad Cove r

age for Manufac tur ing RPE Ce lls

• Br
• ad pr
• te c tion of phar

mac e utic al pr e par ations of RPE c e lls

Co ve rs RPE c e ll suspe nsio ns fo r inje c tio n Co ve rs sc affo lde d RPE laye rs fo r implantatio n Co ve rs po larize d mo no laye rs o f c e lls

• Cove r

s RPE Ce lls de r ive d fr

• m any plur

ipote nt ste m c e ll sour c e

• F

ro m hE SC to iPS c e lls to pluripo te nt ste m c e lls ye t to b e inve nte d

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F ir st Move r and F ir st- in- Clinic E ffor ts T r anslate into Br

• ad F

ir st- to- F ile Pate nts

E ve r y pr ac tic al for mulation for mat for use in human patie nts

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T he r ape utic Pipe line - Othe r Oc ular Pr

• gr

ams

R e tina l Pig me nt E pithe lia l Ce lls

 Ma c ula r De g e ne ra tio n - dry AMD  Re tinitis Pig me nto sa  Pho to re c e pto r pro te c tio n

He ma ng ioblast c e lls

 Isc he mic re tino pa thy

– dia b e tic re tino pa thy, va sc ula r o c c lusio ns

R e tina l Ne ur a l Pr

• g e nitor

c e lls Isola te d Pr

• te c tive F

a c tor s

 Pho to re c e pto r L

• 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 )

Cor ne a l E ndothe lium, Cor ne a l E pithe lium, De sc e me t’s Me mbr a ne

 Co rne a l Dise a se

Me se nc hyma l Str

• ma l Ce lls

 Gla uc o ma , Uve itis  Re tinitis Pig me nto sa  Ma na g e me nt o f Oc ula r Surfa c e s

21 Re tina

Ophtha lmolog y Pipe line E xte nds Be yond RPE

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Plur ipote nt Ste m Ce ll E ye F ie ld Ste m Ce ll RPE

Photore c e ptor Ga ng lion

Proprietary Methods for Deriving Various Cell Types of the Retina

Purity of Resulting Cell Preparations Approaches 100%

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Ce ll line s Pe rc e nta g e of PAX6 + ne ura l ste m c e lls Pe rc e nta g e of Ne stin + ne ura l ste m c e lls

E S line s (N=3) 92%-98% 95%-99% E S line s, b la sto me re te c hno lo g y (N=2) 94%-99% 95%-99% iPS line s, E piso ma l Ve c to r (N=4) 90%-99.6% 96%-100% iPS line s, mRNA (N=2) 92%-98% 96%-100%

• E

va lua te d in multiple hE SC a nd iPS c e lls line s

• Hig hly sync hro nize d c ulture

Highly Reproducible with Various Pluripotent Stem Cell Sources

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Neurosensory Retina – Photoreceptor Replacement

We ha ve de mo nstra te d tha t sub re tina lly inje c te d hE SC- a nd iPSC-de rive d pho to re c e pto r pro g e nito rs c a n

migr ate to c or r e c t anatomic al site in re tina , diffe re ntia te ,

a nd func tionally r

e sc ue vision.

Ca rrying o ut dise a se mo de l POC studie s fo r de mo nstra ting utility in tre a tme nt o f:

• L

a te sta g e ma c ula r de g e ne ra tio n

• Re tinitis Pig me nto sa (RP)
• Nig ht Blindne ss

Unique photore c e ptor prog e nitor (“PhRP- x”) ma inta ins pla stic ity to form both rods a nd c one s

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Whe n de live r e d syste mic ally

• Sc o to pic (sho wn) a nd Pho to to pic E

RG pre se rva tio n o f ro d a nd c o ne func tio n

• E

RG re c o ve ry is c e ll-de pe nde nt (CSA re mo va l re ve rse s E RG re c o ve ry)

• Also o b se rve d pre se rva tio n o f ONL

thic kne ss re la tive to c o ntro l.

Only the PhRP-x pro g e nito rs have

par ac r ine ne ur

• pr
• te c tive ac tivity

– e arlie r stag e hig h purity re tinal pro g e nito rs do no t.

Neurosensory Retina – Neuroprotection

A diffe r e ntiate d func tional phe notype PhRP-x a re pho to re c e pto r pro g e nito rs whic h:

• fo rm b o th ro ds a nd c o ne s
• func tio na lly inte g ra te in ONL
• se c re te a ne uro pro te c tive a g e nt(s)
• ha ve pha g o c ytic a c tivity fo r OS

E d wa rd Myle s – Inte rim Pre sid e nt, CF O a nd E VP o f Co rp De ve lo pme nt

• Dr. Ma tthe w Vinc e nt, Ph.D. – Dir., Busine ss De ve lo pme nt
• Dr. Ro b e rt L

a nza , MD – Chie f Sc ie ntific Offic e r

• Dr. Irina K

lima nska ya , Ph.D. – Dir., Ste m Ce ll Bio lo g y

• Dr. Shi-Jia ng (Jo hn) L

u, Ph.D. – Se nio r Dire c to r o f Re se a rc h E d d y Ang la d e , M.D. – E VP, Clinic a l De ve lo pme nt

• Dr. Ro g e r Ga y, Ph.D. - Se nio r Dire c to r o f Ma nufa c turing

Prove n busine ss le a de rs who c a n de ve lop a nd imple me nt c orpora te stra te g y a nd mone tize a sse ts to ma ximize sha re holde r va lue World- re nowne d sc ie ntific thoug ht le a de rs pushing the c utting e dg e of sc ie nc e to de ve lop importa nt the ra pie s

De e p e xpe r ie nc e in c linic al de ve lopme nt pr

• gr

ams for

• phthalmology dr

ug pr

• duc ts fr
• m

e ar ly thr

• ugh late - and post- mar

ke ting stage s GMP manufac tur ing to e nsur e the highe st quality pr

• duc ts ar

e de live r e d to our patie nts

An E xpe r ie nc e d and De dic ate d Manage me nt T e am

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Mic ha e l He ffe rna n, Cha irma n CE O – Co lle g ium Pha rma c e utic a ls Ro b e rt S. L a ng e r, Sc .D. Institute Pro fe sso r, MIT Zo ha r L

• shitze r

CE O – Pre sb ia , Inc ., & Princ ipa l in Orc ha rd Ca pita l Gre g Pe rry E VP & CF O – E le ve n Bio the ra pe utic s Ala n C. Sha piro F ina nc e Pro fe sso r a nd Cha irma n o f the De pa rtme nt o f F ina nc e a nd Busine ss E c o no mic s (re tire d ) – Unive rsity o f So uthe rn Ca lifo rnia

A World- Cla ss Boa rd of Dire c tors

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