Leading Regenerative Medicine World Stem Cells & Regenerative Medicine Congress May 2012
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 Pluripotent Cell Platforms • Single Blastomere-derived Embryonic Stem Cells • Generating hESC without Destruction of Embryo • Utilizes a single cell biopsy • Our hESC lines exhibit all the standard characteristics and the Final Product Definition: hESC-derived ability to differentiate into the cells of all three germ layers products will be manufactured using a cell both in vitro and in vivo. line made in 2005 from single cell isolated without the destruction of any embryos • Induced Pluripotency Stem Cells (iPS) • Early Innovator in Pluripotency (before iPS was even a term!) • Recipient of National Institutes of Health Director's Opportunity Award • Seminal paper identifying replicative senescence issue for vector-derived iPS cells • Leading publication on protein induced iPS lines - avoids genetic manipulation with nucleic acid vectors • Controlling Filings (earliest priority date) to use of OCT4 for inducing pluripotency 3
RPE Clinical Program
Retinal Pigment Epithelial Cells - Rationale The RPE layer is critical to the function and health of photoreceptors and the retina as a whole. – RPE cells recycle photopigments, deliver, metabolize and store vitamin A, transport iron and small molecules between retina and choroid and maintain Bruch’s membrane – RPE loss leads to photoreceptor loss and eventually blindness, such as dry-AMD – Loss of RPE layer and appears to lead to decline of Bruch’s membrane, leading progression from dry-AMD to wet-AMD RPE cell as Target • Discrete differentiated cell population as target • Failure of target cells results in disease progression 5
Retinal Pigment Epithelial Cells - Rationale • Pigmented RPE cells are easy to identify – aids manufacturing • Small dosage vs. other therapies • The eye is generally immune-privileged site, thus minimal immunosuppression required • Ease of administration, with no separate device approval and straightforward surgical procedure RPE cell therapy may impact over 200 retinal diseases 6
The Unmet Medical Need Probability of progression U.S. Patent Population to late stage AMD within 5 yrs Few Drusen Deposits Grade 0 0.5% Small in size Early Stage AMD (10-15M) Grade 1 3% We process 80 percent of Grade 2 9% all our information Large Drusen Deposits Pigment Change through our eyes. AMD Grade 3 27% Intermediate AMD represents a huge impact (5-8M) Grade 4 43% on QOL in later life Geographic Atrophy: 1M Late Stage AMD CNV Occurrence: 1.2M (1.75M) Risk : Middle-aged adults have about a 2% risk of developing AMD - the risk increases to almost 30% in adults over age 75. Expense : In 2012, the worldwide financial burden of vision loss due to AMD is estimated at >US$350 billion, with >US$250 attributed to direct health care expenditures. On the Rise : Population demographics (“baby boomers”) combined with increased longevity predicts an increase of 50 percent or more in the incidence rate of AMD. 7
RPE Engraftment and Function – Pre-clinical Human RPE cells engraft and align with mouse RPE treated cells in mouse eye treated control RPE cells rescued photoreceptors and slowed decline in acuity in RCS rat 8
GMP Manufacturing • Established GMP process for differentiation and purification of RPE – Virtually unlimited supply – Pathogen-free GMP conditions – Minimal batch-to-batch variation – Characterized to optimize performance – Virtually identical expression of RPE-specific genes to controls Ideal Cell Therapy Product • Centralized Manufacturing • Small Doses • Easily Frozen and Shipped • Simple Handling by Doctor 9
Characterizing Clinical RPE Lots Up-regulation of RPE markers and down-regulation of hESC markers Normal female (46 XX) karyotype of the clinical RPE lot. 10
Characterizing Clinical RPE Lots Quantitative Potency Assay Flow cytometry histogram showing phagocytosis of pHrodo bioparticles Each lot is assessed by phagocytosis (critical function in vivo) of fluorogenic bioparticles. 4 ° C 37 ° C 11
Effects of Pigmentation Melanin content can be measured spectrophotometrically and used to determine the optimal time to harvest and cryopreserve RPE. 2.00 Absorbance at 475nm y = 0.0141x + 0.0007 1.50 1.00 0.50 0.00 0 20 40 60 80 100 120 µg/mL Melanin 12
Phase I - Clinical Trial Design SMD and dry AMD Trials approved in U.S., SMD Trial approved in U.K. 12 Patients for each trial, ascending dosages of 50K, 100K, 150K and 200K cells. • Patients are monitored - including high definition imaging of retina • RPE and photoreceptor activity High Definition Spectral Domain Optical Coherence Tomography (SD-OCT) compared before and after surgery Retinal Autofluorescence Patient 1 Patients 2/3 150K Cells 200K Cells 50K Cells 100K Cells DSMB Review DSMB Review 13
Phase I – Endpoints Safety Assessment acceptable, in the absence of: PRIMARY ENDPOINTS: Adverse event related to cell product Any contamination with an infectious agent Cells exhibiting tumorigenic potential Successful engraftment via: OCT, fundus and other similar imaging evidence ERG showing enhanced activity Evidence of rejection : SECONDARY Imaging evidence that cells are no longer in the correct location ERG showing that activity has returned to pre-transplant conditions ENDPOINTS 14
RPE Clinical Program – to date • US Clinical Trial Sites World-leading eye surgeons and retinal Jules Stein Eye (UCLA) • clinics participate in clinical trials, DSMB Wills Eye Institute • and Scientific Advisory Board Bascom Palmer Eye Institute • • Massachusetts Eye and Ear Infirmary Stargardts: 1st cohort complete, cleared to treat next cohort • Dry AMD: 1st cohort complete, will submit data on patients 2 • & 3 to DSMB in late May • European Clinical Trial Sites • Moorfields Eye Hospital • Aberdeen Royal Infirmary ClinicalTrials.gov US: NCT01345006, NCT01344993 1st SMD patient treated, about to treat patients 2 & 3 • UK: NCTO1469832 15
Surgical Overview • Subretinal injection of 50,000 RPE cells in a volume of 150µl delivered into a pre-selected area of the pericentral macula • Procedure: • 25 Gauge Pars Plana Vitrectomy • Posterior Vitreous Separation (PVD Induction) • Subretinal hESC-derived RPE cells injection • Bleb Confirmation • Air Fluid Exchange Straight-forward surgery that is performed on outpatient basis Drs. Steven Schwartz and Robert Lanza 16
Preliminary Results • Structural evidence confirmed cells had attached and persisted • No signs of hyperproliferation, abnormal growth, or rejection • Anatomical evidence of hESC-RPE survival and engraftment . • Clinically increased pigmentation within the bed of the transplant 17
Preliminary Results Recorded functional visual improvements in both patients. • SMD Patient: BCVA improved from hand motions to 20/800 and improved from 0 to 5 letters on the ETDRS visual acuity chart Dry AMD Patient: Vision improved in the patient with dry age-related macular • degeneration (21 ETDRS letters to 28) Nine Month Follow-up: • Visual acuity gains remain stable for both patients; SMD Patient continues to • show improvement. Similar trends observed for latest AMD and SMD patients • • Update on U.K. SMD01 Patient (3 month follow-up) ETDRS: Improved from 5 letters to 10 letters • Subjective: Reports significantly improved ability to read text on TV • 18
Images of hESC-RPE transplantation site in SMD Patient 1wk post-op pre-transplant 6wk post-op Color fundus photographs Clinically increased pigmentation within the bed of the transplant 19
Images of hESC-RPE transplantation site in SMD Patient 3mo post-op SD-OCT image collected at month 3 show survival and engraftment of RPE Migration of the transplanted cells to the desired anatomical location 20
Phase II/III Design • Design of future studies dependent upon information gathered throughout PI/II study • Efficacy • Patient population less VA impact 20/200? • Multiple Injections • Sub macular Injections Working with our • Further evaluation of I/E criteria experts/investigators in • Potentially less immunosuppression design of studies • Other considerations of efficacy: • New or more sensitive technologies • Possible saline placebo injection (same eye) 21
Recommend
More recommend
