The Prod oduct De Develo elopment Section P Presents Un Unde derwriting ng I Issue ues & I Inno novation Sem emin inar ar July 31-August 1, 2017 | The Westin O’Hare | Chicago, IL Med edical A Adva vances es Moderator: Bruce Dahlquist Pres esen enters: Jason Shelton Andy Singer
About Telomeres and Mortality Jason Shelton, CEO jshelton@telomeredx.com Teloyears.com 1
CEO Update Introduction • Commercial stage, privately held consumer healthcare & molecular dx company. Founded in 2010 by 4 scientists including the winner • of the Nobel Prize in Medicine . • Our core technology: the world’s leading method for measuring Average Telomere Length (ATL), which has been published in peer review. Licensed CLIA Clinical Laboratory . • • Multiple issued patents give broad exclusive protection of our qPCR method. Exclusive worldwide license from University of Utah. • First product, TeloYears , launched 2016. Consumer product for wellness & aging. • Next: a clinically focused premium product that predicts Cardiovascular Disease risk. • HQ in Menlo Park, California. Teloyears.com 2
Big Question…. Can a simple blood test predict mortality? - If one already exists, what an advantage a prospective life insurance buyer could have. Teloyears.com 3
Telomeres Are Parts of Our DNA Telomeres are protective caps …they shorten and fray with age on the ends of our chromosomes... as cells replicate. They comprise thousands of repeats of the nucleotide sequence TTAGGG …they shorten more quickly with oxidative stress / disease Teloyears.com 4
Telomeres Function is to Enable Cell Replication and Prevent Genomic Instability Their job is to trigger cellular senescence (stop replication) and therefore loss of cell regeneration ability. Short Telomeres may indicate: • DNA damage • Tumor initiation Bone Telomere Organ Marrow = High Length Reserve Capacity Low ATL ATL 5 Teloyears.com
Telomere Length Predicts All-Cause Mortality • In largest, most recent, prospective studies • Telomere length measured using the qPCR method • Across a broad age range • Predicted all cause mortality • Independent of patient’s age Teloyears.com 6
History of Telomere Length and Mortality Studied since about 2002 • • First by Richard Cawthon inventor of qPCR method of measuring telomere length at U of Utah – We exclusively own worldwide IP around qPCR method, licensed from U of Utah • Shorter telomeres associated with higher mortality after adjusting for age – 15 years follow up, 143 subjects, age 60-97 Shortest 50% ATL had twice the mortality of – the longest 50% Teloyears.com 7
Telomere Length Predicts All-Cause Mortality • By 2013, there were many studies. • Most showed telomere length to be associated with mortality. • Especially largest studies of general population using qPCR measurement method. Teloyears.com 8
Telomere Length & Mortality in General Population • By 2015, large studies of 64K+ subjects in the general population (published in Journal of NCI) • Telomere length measured using qPCR associates with higher mortality. – The 10% with the shortest telomeres were dying at 1.4X the rate of the 10% with the longest telomeres, a result that was overwhelmingly statistically apparent (p<2×10-15) Teloyears.com 9
By 2017, Telomere Length Predicts All-Cause Mortality • By 2017, telomere length measured using qPCR associates with higher mortality beyond its association with age . Teloyears.com 10
Telomere Length Predicts All-Cause Mortality Telomere Length measured using qPCR can identify those groups of people with higher risk of dying. • The bottom line of the new, large studies is the extra predictive power of telomere length , even after all these other lifestyle and indicator variables are factored out. • After correcting for smoking, for age, for weight and cholesterol and exercise habits, there is still a powerful negative correlation between telomere length and mortality. Teloyears.com 11
Telomere Length and Chronic Disease Teloyears.com 12
Telomere Length Predicts Heart Disease Source: Haycock Ph., Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis, the BMJ, 2014 Teloyears.com 13
ATL is Well Established in Predicting CVD 10-year, prospective study (n=800) Low ATL = More risk Low ATL High ATL = Less risk High ATL “Cellular Aging Reflected by Leukocyte Telomere Length Predicts Advanced Atherosclerosis and CVD Risk”. 800 healthy men and women 45-84 y followed 10 y prospective Bruneck Study Willeit et al., 2010, Journal of the AHA, ATVB, 30: 1649-1656 Teloyears.com 14
Telomere Length and Cardiovascular Disease A meta-analysis of 27 studies: > 6500 people • Conclusions: Shortened leukocyte telomere length demonstrates a significant association with stroke, myocardial infarction and type 2 diabetes mellitus. (D’Mello et al Circ Cardiovasc Genet . 2015;8:82-90. DOI: 10.1161/CIRCGENETICS.113.000485.) • Dozens of studies have shown the link between short leukocyte telomeres and heart disease. Teloyears.com 15
Diabetes • Telomere Length Predicts all-cause mortality in patients w/ Type 1 diabetes. (Astrup et al. Diabetologis, 2010, 53(1) 45-8) • Studies established that short telomere length is associated with future development of type 2 diabetes independently of known type 2 diabetes risk factors . Individuals in the lowest quartile of leukocyte telomere length were at almost twice the risk of developing diabetes compared with those with longer telomeres. (Zhao et al, Diabetes 2013: 63: 354-362 pmid 10911978) Teloyears.com 16
Easy Sample Collection for Telomere Length? • At-home sample collection • Drop of blood from a finger stick, returned via US Mail – Could also aliquot from EDTA tube • $89 retail price Teloyears.com 17
What Can You Do About Your Telomere Length? Studies show telomere length can be improved by lifestyle changes. • “ In this large study, greater adherence to the Mediterranean diet was associated with longer telomeres. These results further support the benefits of adherence to the Mediterranean diet for promoting health and longevity. ” – The British Medical Jounal “Mediterranean diet and telomere length in Nurses’ Health Study: population based cohort study” (see: http://www.bmj.com/content/349/bmj.g6674), see conclusion. • “C omprehensive lifestyle intervention was associated with increases in relative telomere length after 5 years of follow-up, compared with controls …” – The Lancet Oncology (http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2813%2970366-8/fulltext), see conclusion. • “ Leukocyte telomere length was positively associated with increasing physical activity level in leisure time .” – The Archives of Internal Medicine “The association between physical activity in leisure time and leukocyte telomere length” (see: https://www.ncbi.nlm.nih.gov/pubmed/18227361) see results. “ Overall, PA [physical activity] was significantly and meaningfully associated • with telomere length in U.S. men and women. " – Preventative Medicine “ Physical activity and telomere length in U.S. men and women: An NHANES investigation ” (see: http://www.sciencedirect.com/science/article/pii/S0091743517301470 ), see conclusion. Teloyears.com 18
Committed to Educating on Telomeres • Visit TeloYears.com to learn more on our Telomere Learning Center • 20,000+ papers on Pubmed.gov Teloyears.com 19
Could Telomere Testing Be Used to Reclassify Life Insurance Buyers? Super Preferred / Elite Class Longer Telomeres Preferred Class Standard Class Substandard Class Decline Shorter Telomeres • Seems to be a very reasonable basis for further study. Teloyears.com 20
QUESTIONS Teloyears.com 21
THANK YOU. JASON SHELTON CEO TELOMERE DIAGNOSTICS, INC. JSHELTON@TELOMEREDX.COM Teloyears.com 22
ATL Has Weak Correlation with Age • Data generated using our current qPCR assay on n=313 subjects’ blood samples. Found low correlation (R- • squared = 0.3) between Age and ATL in the relevant group (healthy people aged 20+). • Makes ATL a good candidate to be an predictive biomarker that is independent of age. 23 Teloyears.com
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