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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 OHare | Chicago, IL Med edical A Adva vances es Moderator:

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The Prod

  • duct 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

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Teloyears.com

About Telomeres and Mortality

Jason Shelton, CEO jshelton@telomeredx.com

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Teloyears.com

CEO Update

Introduction

  • Commercial stage, privately held consumer

healthcare & molecular dx company.

  • Founded in 2010 by 4 scientists including the winner
  • f 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.

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Teloyears.com

Big Question….

Can a simple blood test predict mortality?

  • If one already exists, what an advantage a

prospective life insurance buyer could have.

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Teloyears.com They comprise thousands of repeats

  • f the nucleotide sequence TTAGGG

Telomeres Are Parts of Our DNA

Telomeres are protective caps

  • n the ends of our chromosomes...

…they shorten and fray with age as cells replicate.

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…they shorten more quickly with

  • xidative stress / disease
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Teloyears.com

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Short Telomeres may indicate:

  • DNA damage
  • Tumor initiation

Bone Marrow Low ATL High ATL

Telomeres Function is to Enable Cell Replication and Prevent Genomic Instability

Telomere Organ Length Reserve Capacity

=

Their job is to trigger cellular senescence (stop replication) and therefore loss

  • f cell regeneration ability.
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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

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Teloyears.com

History of Telomere Length and Mortality

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  • 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%

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Teloyears.com

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.

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Teloyears.com

Telomere Length & Mortality in General Population

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  • 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)

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Teloyears.com

By 2017, Telomere Length Predicts All-Cause Mortality

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  • By 2017, telomere length

measured using qPCR associates with higher mortality beyond its association with age.

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Teloyears.com

Telomere Length Predicts All-Cause Mortality

Telomere Length measured using qPCR can identify those groups

  • f 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.

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Teloyears.com

Telomere Length and Chronic Disease

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Teloyears.com

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Source: Haycock Ph., Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis, the BMJ, 2014

Telomere Length Predicts Heart Disease

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Teloyears.com “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

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ATL is Well Established in Predicting CVD

10-year, prospective study (n=800)

Low ATL = More risk High ATL = Less risk

High ATL Low ATL

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Teloyears.com

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.

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Teloyears.com

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)

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Teloyears.com

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

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Teloyears.com

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.

  • “Comprehensive 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.

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Teloyears.com

Committed to Educating on Telomeres

  • Visit TeloYears.com to learn more on our Telomere Learning Center
  • 20,000+ papers on Pubmed.gov

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Teloyears.com

Could Telomere Testing Be Used to Reclassify Life Insurance Buyers?

Super Preferred / Elite Class Preferred Class Standard Class Substandard Class Decline

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Longer Telomeres Shorter Telomeres

  • Seems to be a very reasonable basis for further study.
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Teloyears.com

QUESTIONS

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Teloyears.com

THANK YOU.

JASON SHELTON CEO TELOMERE DIAGNOSTICS, INC. JSHELTON@TELOMEREDX.COM

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Teloyears.com

ATL Has Weak Correlation with Age

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  • 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.