Leading the Regenera-ve Medicine Revolu-on Hayflick Rewound: Implica-ons of Reversing the Aging of Human Cells Michael D. West, Ph.D. Mensa Annual Gathering June 29, 2016 NYSE MKT: BTX Safe Harbor Statement The maUers discussed in this presenta-on include forward looking statements which are subject to various risks, uncertain-es, and other factors that could cause actual results to differ materially from the results an-cipated. Such risks and uncertain-es include but are not limited to the success of BioTime in developing new stem cell products and technologies; results of clinical trials of BioTime products; the ability of BioTime and its licensees to obtain addi-onal FDA and foreign regulatory approval to market BioTime products; compe--on from products manufactured and sold or being developed by other companies; the price of and demand for BioTime products; and the ability of BioTime to raise the capital needed to finance its current and planned opera-ons. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "an-cipates," "expects," "es-mates") should also be considered to be forward-­‐looking statements. Forward-­‐looking statements involve risks and uncertain-es, including, without limita-on, risks inherent in the development and/or commercializa-on of poten-al products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. As actual results may differ materially from the results an-cipated in these forward-­‐looking statements they should be evaluated together with the many uncertain-es that affect the business of BioTime and its subsidiaries, par-cularly those men-oned in the cau-onary statements found in BioTime's Securi-es and Exchange Commission filings. BioTime disclaims any intent or obliga-on to update these forward-­‐looking statements. 2 The Immortal Renewal of Life 3 The Immortal Renewal of Life The Evolution of Aging
From: August Weismann (1891) 4 The Immortal Renewal of Life The Evolution of Aging
5 The Immortal Renewal of Life The Evolution of Aging
6 The Immortal Renewal of Life The Evolution of Aging
7 Origins of Cellular Gerontology 8 Origins of Cellular Gerontology 9 Origins of Cellular Gerontology Alexis Carrel: First U.S. Nobel Laureate
10 Origins of Cellular Gerontology Carrel, Lindbergh, & Regenerative Medicine
11 Origins of Cellular Gerontology Leonard Hayflick’s Discovery
12 Origins of Cellular Gerontology 13 Origins of Cellular Gerontology “The inference that death of the cells in some of the un-­‐ infected cultures is due to “senescence” at the cellular level” seems notably rash. The largest fact to have come out from -ssue culture in the last fily years is that cells inherently capable of mul-plying will do so indefinitely if supplied with the right milieu in vitro.” 14 Origins of Cellular Gerontology 15 Origins of Cellular Gerontology 16 Origins of Cellular Gerontology Evidence Aging is not that Complex
Werner Syndrome Progeria 17 Origins of Cellular Gerontology Telomeres as a Clocking Mechanism
18 Origins of Cellular Gerontology Telomeres as a Clocking Mechanism
19 Origins of Cellular Gerontology Telomeres as a Clocking Mechanism
TRF Length
(kbp)
Population Doublings
15
Somatic
(Telomerase -)
10
5
Neonatal
Age
20 Hayflick
Limit
22 34 43 55 65 72 82 90
Decreasing Telomere Length With Age
Germ-Line
(Telomerase +)
Origins of Cellular Gerontology Telomerase as the Immortality Enzyme
21 Origins of Cellular Gerontology Telomerase as the Immortality Enzyme
22 Origins of Cellular Gerontology Telomerase as the Immortality Enzyme
23 Origins of Cellular Gerontology Telomerase as the Immortality Enzyme
24 Origins of Cellular Gerontology Rescue with T’ase & Reprogramming WRN 25 TRF2 Telomeric Repeats LMNA TRF2 Origins of Regenera-ve Medicine Can We Culture Immortal Germ-Line Cells?
Germ-­‐Line Cells EG
ES
EG
ES
Mortal Soma-c Cells 26 Origins of Regenera-ve Medicine Can We Culture Immortal Germ-Line Cells?
ES
27 Origins of Regenera-ve Medicine Can We Culture Immortal Germ-Line Cells?
28 Origins of Regenera-ve Medicine Can We Culture Immortal Germ-Line Cells?
29 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through Cloning?
30 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through Cloning?
31 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through Cloning?
32 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through Cloning?
“I recall when the news first came out, somebody said that Dolly was a sheep in lamb’s clothing. I think that’s an appropriate quote now.” -­‐ Jerry Shay 1999 33 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through Cloning?
Science (2000) 288: 665 34 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through Cloning?
35 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through Cloning?
36 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through Cloning?
37 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through Cloning?
38 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through
Transcriptional Reprogramming?
39 Origins of Regenera-ve Medicine Can We Reverse Aging & Development through
Transcriptional Reprogramming?
40 Applica-ons of Regenera-ve Medicine Treating Age-Related Disease (Obesity/Type II Diabetes)
41 Applica-ons of Regenera-ve Medicine Treating Age-Related Disease (Obesity/Type II Diabetes)
42 Applica-ons of Regenera-ve Medicine Treating Age-Related Disease (Osteoarthritis)
Experimentally-­‐ induced trauma OTX-­‐CP03 4 weeks 43 Applica-ons of Regenera-ve Medicine Treating Age-Related Disease (Macular Degeneration)
With age >50, loss of RPE cells can cause dry or wet AMD Photoreceptor func-on, angiogenesis inhibi-on depend on re-nal pigment epithelial (RPE) cells Strategy is off-­‐the-­‐shelf injec-on of young cells as a one-­‐-me therapy Human embryonic stem cell-­‐derived re-nal pigment epithelial cells can integrate into subre-nal space to replace missing RPE cells Young RPE cells make a natural angiogenesis inhibitor (PEDF) 44 Photoreceptors
Retinal Pigment
Epithelium (RPE)
Choroid
Drusen
Applica-ons of Regenera-ve Medicine Treating Age-Related Disease (Ischemic Disorders)
45 48 HOURS
96 HOURS
72 HOURS
168 HOURS
Applica-ons of Regenera-ve Medicine •  Scalable source of all human cell types •  Immortal cells allow sophis-cated gene-c modifica-ons 46 Applica-ons of Regenera-ve Medicine •  Scalable source of all human cell types •  Immortal cells allow sophis-cated gene-c modifica-ons 47 Personalized Applica-ons -­‐ Regenomics •  Scalable source of all human cell types •  Immortal cells allow sophis-cated gene-c modifica-ons Embryonic = Regenera-ve Current Topics in Developmental Biology, Volume 103:229
49 Induced Tissue Regenera-on (iTR) Can We Induce Embryonic Regeneration?
50 Induced Tissue Regenera-on (iTR) Can We Induce Embryonic Regeneration?
51 AI & Deep Neural Networks Basic Concepts
52 AI & Deep Neural Networks Basic Concepts
hUp://cs.stanford.edu/people/karpathy/deepimagesent/ 53 AI & Deep Neural Networks Basic Concepts
54 Deep Neural Networks Trained on Aging 55 Induced Tissue Regenera-on (iTR) Deciphering Mechanisms using Artificial Intelligence
56 The Urgent and Growing Need Aging: The demographic trend of our time
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57 Approx 80% of health care costs associated with degenerative
disease.
Many degenerative diseases associated with loss or dysfunction
of cells associated with aging, therefore, often only the symptoms
are currently drugable.
Summary •  Important insights into the biology of aging can be gleaned from the study of immortal germ-­‐line cells. •  Pluripotent stem cells should allow cell-­‐based strategies to repair age-­‐related degenera-ve disease. •  iTR could be the most powerful technology yet iden-fied. •  Deep Learning technology may accelerate the research and is available online at hUp://
discovery.lifemapsc.com/ 58 Leading the Regenera-ve Medicine Revolu-on NYSE MKT: BTX 1010 Atlan-c Ave, Suite 102 Alameda, CA 94501 510-­‐521-­‐3390 59