Lineage Cell Therapeutics, Inc. · AMEX:LCTX
Lineage Cell Therapeutics — Biotime — Technical Presentation (May 2019)
44 slides from Lineage Cell Therapeutics's technical presentation, May 2, 2019
Slide 1: Phase I/IIa Study of hESC-Derived RPE Cells in Dry AMD: Interim Results
Phase I/lla Study of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium Cells Transplanted Subretinally in Subjects with Advanced Dry-Form Age-Related Macular Degeneration: Interim Results Eyal Banin, MD, PhD Center for Retinal and Macular Degenerations (CRMD) Department of Ophthalmology,
Slide 2: Financial disclosures
Financial disclosures Eyal Banin: Patent, Consultant; Adiel Barak: Investigator; David Boyer: Investigator, Consultant; Diana V. Do: Investigator, Consultant; Rita Ehrlich: Investigator; Tareq Jaouni: Investigator; Richard McDonald: Investigator; David G. Telander: Investigator; Maria Gurevich: Cell
Slide 3: Participating principal investigators and sites
Participating principal investigators and sites Adiel Barak, Sourasky Medical Center, Tel Aviv, Israel David Boyer, Retina Vitreous Associates Medical Group Los Angeles, CA, USA Diana V. Do, Byers Eye Institute, Stanford, Palo Alto, CA, USA Rita Ehrlich, Rabin Medical Center, Petah Tikva, Israel Tar
Slide 4: hESC-Derived RPE Cells - OpRegen
Human Embryonic Stem Cells (hESC) Derived Retinal Pigmented Epithelial (RPE) Cells - OpRegen® Directed differentiation of hESC to RPE under GMP conditions RPE cells Clinical grade Embryonic Neural Spheres w/ stem cell clusters pigmented areas
Slide 5: In Vitro Pre Clinical Data: Identity and Functionality
In Vitro Pre Clinical Data: Identity and Functionality In-Vitro Immuno- hESCs OpRegen Identity And Purity Assay a 10" 0.06% CRLBP 99.5% CRLBP | 2 2 PMEL17 y PMELI7~— z Positive 1 Positive =) 10° 10 r T rT 10' 10! 10° 1c 10° PMEL 17 Functionality: Phagocytosis Assay 10 0.7% POS Positive ai? 99.4% POS
Slide 6: In-Vivo Pre Clinical Data: Efficacy
In-Vivo Pre Clinical Data: Efficacy Optomotor Tracking Threshold In RCS Rats Untreated =u BSS+ = 25K = 100K = 200K Spatial frequency (cycles per degree) os 0.4 0.3 0.2 04 P100 Age tii P150 Untreated =Bss+ = 28K Cells, = 100K Cells = 200K Cells i P200 a ao Cones per image (775 um) TJ McGill, et al. T
Slide 7: RCS rat and pig retina post transplantation
RCS rat Pig retina 19 weeks post transplantation 3 months post transplantation anti- human Nuclei Human specific marker Tra-1-85 Nuclei were counter-stained with DAPI
Slide 8: Study design, population, management
Study design, population, management Parameter Cohort 1-3 Cohort 4 N=12 N=12 Phase/design Phase I-lla; staggered design; IND (NCTO2286089) Duration Screening up to 8 Weeks; FU — 1 year; long term FU — 4 years Management Central reading/central labs/ Independent DSMB/Advisory Committees Treated disea
Slide 9: Study assessments
Study assessments [Endpoints Assessments Primary: Safety Adverse Events Secondary: Anatomical and Functional Clinical / Imaging Outcomes Ocular findings * BCVA * OCT ° FAF ¢ Fundus Photography « FQ25 00I" ° Reading Speed Test* * Microperimetry* * Ongoing in Cohort 4 subjects
Slide 10: OpRegen Transplantation
OpRegen® Transplantation a ys a ny) ‘ sie bo
Slide 11: Representative Color Fundus Imaging
Representative Color Fundus Imaging
Slide 12: Rapid Healing of Injection Site
Rapid Healing of Injection Site Subject 1 Subject 2 Subject 3 Baseline ; Precise location of subretinal injection indicated by red arrow 1 Day Post-op 2 Weeks Post-op 3m 1 Year Post-op
Slide 13: Study Update
Study Update 13
Slide 14: Study status
Study status * Cohort 1-3 recruitment completed * Cohort 4 recruitment ongoing [cohort N (%) of subjects screened 54 (100%) N (%) of screening failures 42 (78%) N (%) subjects treated 12 (22%) N (%) subjects dropout 1(8 %) Post-implantation cumulative FU period 15.1 years Mean FU (days) 339.3 (SE 29
Slide 15: Baseline characteristics for cohorts
Baseline characteristics for cohorts 1-3 and 4 Age: mean (SD/min-max) 78.3 (+ 8.2/64.8-92.2) years 77.1 (+ 3.1/74.6-80.6) years ETDRS BCVA: mean (SD/min-max) 23.7(+ 11.7/0-39) letters* 55 (+ 13.5/42-59) letters* GA area: mean (SD/min-max) 12.7(+ 7/6-30) mm? 7.1 (+ 1.4/5.5-8.3) mm? Known duration of
Slide 16: Primary endpoints: safety and tolerability - Part I
Primary endpoints: systemic and ocular safety and tolerability-Part | ¢ Safety and Tolerability ¢ BCVA remained largely stable over time in treated eyes * One cohort 4 subject experienced a marked improvement * One cohort 4 subject experienced a sharp decline due to ERM, BCVA returned to few letters
Slide 17: Primary endpoints: safety and tolerability - Part II
Primary endpoints: systemic and ocular safety and tolerability-Part II * Ocular Safety and Tolerability * The most reported AEs were related to Eye Disorders System; most frequent were: Conjunctival Hemorrhage after surgery — reported by 8/ 15, recovered rapidly Eye irritation — reported by 1 subjec
Slide 18: Cohorts 1-3: BCVA change from baseline over time
Cohorts 1-3: BCVA change from baseline over time (n=12) BCVA MEAN CHANGE FROM BASELINE - TREATED AND FELLOW EYE & | BCVA Change (# of ETDRS lettes) | Nn o Ly q N o é o uw 10 15 20 25 Time post implantation (months) —Treated Eye Average —Fellow Eye Average
Slide 19: Cohorts 1-3: GA area change from baseline over time
Cohorts 1-3: GA area change from baseline over time (n=12) MEAN GA AREA CHANGE OVER TIME - TREATED AND FELLOW EYE 15 = bo c 10 o S — ee ve <q <x 0 = 1U) 5 0 5 10 15 20 25 30 35 Time (months) —tTreated Eye Average —-Fellow Eye Average GA area as measured from FAF images by central reading center
Slide 20: Cohort 4: BCVA change from baseline over time
Cohort 4: BCVA change from baseline over time (n=3) BCVA CHANGE FROM BASELINE -TREATED EYE x 8 Treated Eye BCVA Change (# of ETDRS lettes) rr) 0 1 2 3 4 5 6 7 8 9 Time post implantation (months) ft —Pt2 —Pts BCVA CHANGE FROM BASELINE -FELLOW EYE 30 8 Fellow Eye BCVA Change (# of ETDRS lettes) S | Ti
Slide 21: Cohort 4: GA area change from baseline over time
Cohort 4: GA area change from baseline over time (n=3) GA AREA CHANGE OVER TIME - TREATED EYE Treated Eye GA Area Change (mm?) ° 0 1 ial } 4 5 6 7 8 9 10 Gy Time Point (months) GA AREA CHANGE OVER TIME - FELLOW EYE Fellow Eye GA Area Change (mm?) ° | 0 1 2 > 4 5 6 7 8 = 10
Slide 22: Study outcomes of secondary endpoints
Study outcomes of secondary endpoints: Imaging findings that may support presence and survival of transplanted cells ¢ As per Reading Center, 10 out of 15 subjects show new subretinal hyperpigmentation after hESC-RPE transplantation ¢ In 7 out of 15 cases, irregular hyper-reflectivity at RPE level o
Slide 23: Baseline Months
IR Baseline 12 Months 23
Slide 24: Baseline
Baseline ie i clea a 1 Month GA border, Irregular hyper-reflectivity
Slide 25: Baseline
Baseline Baseline
Slide 26: Months
24 Months GA border, Irregular hyper-reflectance =
Slide 27: OpRegen engraftment and survival in swine
OpRegen engraftment and survival in swine 27
Slide 28: Subject
Subject 2 GA at baseline (red-violet) Versus 36 months (light blue)
Slide 29: Subject
Subject 9 GA at baseline (red-violet) Versus 12 months (light blue)
Slide 30: Subject
Subject 8 Baseline Baseline a 12 Months Bleb border, Subretinal injection location,
Slide 31: Selected images of Drusen reduction
Selected images of Drusen reduction Treated Area 15 months , Subretinal injection location,
Slide 32: Subject 8: Baseline vs months
Subject 8: Baseline vs 12 months — Shows changes are being maintained
Slide 33: Case Report - Cohort 4, Subject
. Case Report- Cohort 4, Subject 14 Baseline Intra OP bleb 2 months 3 months (2 weeks before ERM peel) (2 weeks after ERM peel)
Slide 34: Months before and after ERM peel
2 months (2 weeks before ERM peel) 3 months (2 weeks after ERM peel)
Slide 35: Case Report
un x= = ‘= ° € a Baseline Case Report
Slide 36: Case Report
Case Report
Slide 37: Case Report months
Case Report 9 months Baseline
Slide 38: Baseline - Nasal Border of GA
Baseline oA Nasal Border of GA
Slide 39: Case Report
Case Report
Slide 40: Case Report - Superior Border of GA
Case Report Superior Border of GA
Slide 41: Case Report - Inferior Border of GA
Case Report Baseline = Inferior Border of GA
Slide 42: Summary (I)
Summary (I) * Following subretinal transplantation of OpRegen (hESC-RPE) in suspension there is rapid healing of the injection sites, and visual acuity remained largely stable throughout the study with follow-up of up to 36 months in the first-treated subjects * Subretinal pigmentation in the treate
Slide 43: Summary (II)
Summary (II) In general, subretinal transplantation of OpRegen appears well tolerated to date and there are signs indicative of improved retinal structure in the treated areas in some cases. This requires additional follow-up and observation Cohort 4 is ongoing, treating subjects with better vision,
Slide 44: Thank you!
Thank you!