TELOMERESUnlocking The Aging Code

Stephen Matlin, CEO

January 23, 2017

1. What are telomeres?

2. Telomeres and aging

3. Telomerase and cancer

4. Life Length overview

AGENDA

What are telomeres and

why are they important?

TELOMERESare the protective caps at the ends of

chromosomes which gradually get shorter

with age. By measuring telomere length you

can see how fast you are aging.

As cells replicate… Telomeres shorten… And the individual ages…

HOW WELL ARE YOU

AGING?

CVD

Cancer

Metabolic

Diseases

Stem Cells

DISEASE LEVEL

ORGAN LEVEL

CELL LEVEL

FertilityStress

Arthritis

CNS

SHORT

TELOMERES

DNA DAMAGE

DNA DAMAGE

Senescence and apoptosis

Why should we care about telomeres?

ENVIRONMENTAL FACTORSEnvironmental factors, including individuals’

lifestyle choices, play an even larger role.

GENETICSShort telomeres are contributing

factor of virtually all age-related

diseases. Genetics play a partial

role in determining telomere

length.

CHANGE LIFESTYLE HABITS.

BUILD A PERSONALIZED PROGRAM FOR EACH PATIENT

RESULTS

RECEIVED

STRATIFY RISK BY

COMPARING RESULTS

WITH PATIENTS’ MEDICAL

HISTORY

Telomeres are well established as a major contributing

factor and cause of age-related diseases

April, 2015

Julio, 2014

June, 2010

April, 2016

June, 2016

October, 2015

May, 2015

Cellular senescence

Stem cell exhaustion

Loss of

proteostasis

Genomic

instability

Telomere attrition

Deregulated

nutrient-

sensing

Mitochondrial

dysfunction

Causes of aging

Epigenetic

alterations

Altered

intercellularcommunication

Modified from Lopez-Otín, Blasco, Partridge, Serrano & Kremer, Cell, 2013

Cellular senescence

Stem cell exhaustion

Loss of

proteostasis

Genomic

instability

Telomere attrition

Deregulated

nutrient-

sensing

Mitochondrial

dysfunction

Epigenetic

alterations

Altered

intercellularcommunication

Causes of aging

Modified from Lopez-Otín, Blasco, Partridge, Serrano & Kremer, Cell, 2013

Clearance of

senescent cells Stem cell-based

therapies

Activation of

chaperones and

protease systems

Anti-

inflammatory

drugs

Elimination of

damaged cells

Telomerase

reactivation

Dietary

restriction

Mitophagy

Epigenetic drugs

Modified from Lopez-Otín, Blasco, Partridge, Serrano & Kremer, Cell, 2013

How can we reverse aging?

• Telomerase operates at the end of the chromosome synthesizing

telomere DNA.

• Without telomerase present, the chromosome is shortened each time

the cell divides.

What is telomerase?

• This gene, telomerase, is silenced

after birth. However cancer cells

manage to reactivate telomerase,

thus escaping the mortal fate of adult

cells and becoming immortal.

• In somatic cells telomeres gradually become shortened due tothe end-replication problem during DNA duplication associatedwith cell division.

• Once telomeres reach a critical length they no longer protect theDNA, the chromosomes become uncapped and as aconsequence senescence is triggered.

• Cancer cells must overcome this crisis stage to maintain theirtelomeres and achieve immortality. They do so by activatingtelomerase (in about 85% of tumors) or by the use of alternativelengthening of telomeres (ALT) through telomerase-independent mechanisms (about 15%).

Cancer cells must maintain their telomeres to become immortal

Image taken from: Fernández-Garcia I. et al. Telomeres and Telomerase in Lung Cancer.

Cancer cells must maintain their telomeres to become immortal

• A molecule developed by Geron, now licensed to J&J, to target malignant

progenitor cell proliferation.

• Seeks to halt tumor progression and kill cancer

Telomerase and cancerImetelstat®

• This products is a specific inhibitor of

telomerase. Is the first telomerase inhibitor to

advance to clinical development for:

Breast cancer

Lung cancer

Image taken from www.geron.com

Boccardi & Herbig, EMBO Molecular Medicine, 2012

Bernardes et al. , EMBO Molecular Medicine, 2012

Telomerase reactivation / upregulation

Efforts are underway to find methods to cause transitory upregulation of telomerase in order to reset the

biological (age) of cells to increase organs regenerative potential and hence life span of organism.

About Life Length

About Life Length

• The world leader in providing telomere diagnostics and telomerase activity measurements

• The only U.S. Federally FDA certified “CLIA” Clinical Laboratory in Spain (CLIA License # 99D2112462); as well as ISO

15189 Accreditation, A2LA Accreditation and Spanish Ministry of Health Certification as a Clinical Diagnostic

Laboratory. Life Length is the only laboratory in Europe to be both CLIA and ISO 15189 certified

• Originally a spin-off of the prestigious Spanish National Cancer Research Institute (CNIO)

• Life Length has developed a unique and proprietary high-content screen technology

• Our robust, sensitive and reproducible technology can be combined with other analyses to provide a

comprehensive picture of a patient’s health

• Life Length has received two important awards since its founding:

Best new technology company in Spain– award given by leading Spanish business

newspaper Expansión – 2013

Best company for technological innovation in

Madrid – award given by the Fundación Madri+d –

2013

TAT as an academic and clinical research technology

Reflecting the quality and relevance of our unique technology, Life Length is currently

participating as a partner in important E.U. funded projects focused on improving healthcare.

Environmental influences in prenatal life have a major impact on brain aging and age-

associated brain disordersBRAINAGE

Utility of omic-based biomarkers in characterizing older individuals at risk for frailty, their

progression to disability and general consequences to health and well-beingFRAILOMIC

Study on 8,000 identical twins to identify predictors of agingEUROBATS

Clinical studies for the validation of telomere biology biomarkers in early diagnosis and prognostic

in cancerONCOCHECK

Life Length has been awarded €3.1 million by the European Union as a Phase 2

grant under the prestigious and highly competitive Horizon 2020 for its

ONCOCHECK project which will fund clinical studies of this valuable biomarker

in cancer treatment.

Life Length has received €3.1 million from the H2020

European Union project

Key Metrics of ONCOCHECK

Hospitals involved: 28+ public hospitals

Number of patients in study: 2,300 (2,200+ adults and 100+ children)

Types of cancer: Solid tumors and hematopoietic cancers in children; prostate, lung and CLL and solid

tumors in adults, among others.

Time points: Blood samples to be taken from patients during 24 months

Output: Demonstration of the value of telomere related markers in cancer patient management.

Life Length advisors include scientists from renowned international institutions:

• Southwestern Medical Center

• Yale University

• Barts and The London School of Medicine (UK)

• Juntendo University (Japan)

• Georgetown University

Life Length has world-class Scientific Advisory Board

Life Length serves clients in three main

business segments

Physicians

As the reference test

for use by physicians

and individuals in

preventive personalized

healthcare and for its

clinical and diagnostic

value in aging and age-

related diseases

B2B

As an important new

tool for pharma and

biotech R&D, clinical

trials and product

development for new

medicines, animal

health and nutrition

Academia

As an academic and

science research

technology.

Collaborations with

prestigious institutions

in U.S. and E.U.

Life Length has established an international network of laboratory

partners and currently provides services in over 35 countries

including North American and Europe.

Laboratory partnerships in place

Multiple sample processing

Single sample processing

Average telomere length Percentage of short telomeres

Population of cells Population of cellsSingle cells Single cells

Flow cytometry

Q-PCR

Q-FISH

Telomapping (tissue)

TAT® (blood)

Methods for measuring telomere length

Scalability

Clinical Utility

• A clinically accredited high-complexity assay:

For physicians and individuals• Patient care in preventive and personalized medicine

• For early detection of age-related and chronic diseases

For pharma, biotech and nutraceutical/supplement companies• Drug and supplement R&D and screening

• Clinical trials where telomere biology is a relevant marker

Thank you