TESTBED FOR NEXT GENERATION REASEARCH & INNOVATION

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T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

ACADEMIC RESEARCH INDUSTRY

PUBLIC-PRIVATE PARTNERSHIPS FOR NEW INNOVATIONS

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PHARMA R&D SPEND

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Important decisions in drug discovery

Target Selection

and Validation

Screening Pre-clinical Phase I Phase II Phase III Phase IV

What Target?

Which Patients?

The Problem:

It difficult to develop novel therapies that differentiate from standard of care

>90% of compounds in clinical trials fail due to lack of safety and efficacy

Picking the right target is the most important decision we make

Sally John, Biogen

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Very large collections combining genome data with health data is needed

DATA RESOURCE WITH GENOME AND HEALTH

INFORMATION

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

OPPORTUNITY FOR MULTIPLE STUDY DESIGNS

POPULATION ISOLATE

HEALTHREGISTERS

BIOBANKS GENOME DATA

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T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Toimimaton geeni

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Suojaavat Geenit

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

EARLY SETTLEMENT • 2000-10 000 years ago• South and Coast

LATE SETTLEMENT• 16th century• multiple bottle necks

EXPANSION • 18th century – population 250 000• Today – population 5.4 million

EARLYSETTLEMENT

LATESETTLEMENT

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Opportunity to identify disease associated low frequency variants

Population isolate

• Finns have dramatically fewer rare DNA variants than other Europeans

• Some specific DNA variants jump to unusually high frequencies

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Two LPA LoF variants(35 000 Finns)

LoF variant Frequency in Finns Frequency in non Finns

LPA1(4974) 2.8% 0.47%

LPA2(4289) 4.8% 3.6%

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Loss-of-function variants in LPA protects from Coronary Heart Disease

Finnish enriched DNA variant lowers LPA levels

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Loss-of-function variants in LPA protects from Coronary Heart Disease

Each copy of LPA lowering variant lowers CHD risk by 15-20%

Finnish enriched DNA variant lowers LPA levels

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Two LPA LoF variants(35 000 Finns)

LoF variant Frequency in Finns Frequency in non Finns

LPA1(4974) 2.8% 0.47%

LPA2(4289) 4.8% 3.6%

227 Finns homozygous/compound het

Linking to National Health Records

No sign of increased morbidity

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Truncating mutations in SLC30A8 seen 3x more often in healthy controls than diabeticsSTRONG protection against diabetes !!!

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

50% of all known Finnish R138X carriers are around Jakobstad

And 12, i.e. 50% of them, seem to have a connection to an island called Larsmo

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

Recalling SLC30A8 carriers

• More than 75% of individuals recalled have returned for extensive phenotypinginvolving a test meal and numerous blood draws over three hours

• 73 individuals already successfully studied under this protocol

• Almost all are healthy controls with no self-interest in the research

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

These provide precise clues to interventions that could be safe and effective

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

OPPORTUNITY FOR MULTIPLE STUDY DESIGNS

POPULATION ISOLATE

HEALTHREGISTERS

BIOBANKS GENOME DATA

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T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

NATIONAL REGISTERS

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

EXAMPLE OF HEALTH HISTORIES FROM TWO PERSONS FROM THE NATIONAL BIOBANKS WITH A 40 YEAR FOLLOW-UP

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

OPPORTUNITY FOR MULTIPLE STUDY DESIGNS

POPULATION ISOLATE

HEALTHREGISTERS

BIOBANKS GENOME DATA

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T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

BIOBANK ACT + SOCIAL SECURITY NUMBER

BIOBANK

CLINICAL STUDIES

RECALLING

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

IPHG

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

IPHG-hanke• Tutkitaan noin 30 pharma kollaboraattorien valitsemaa

geeniä• Finrisk, Terveys 2000, HBCS, Laseri (Young Finns), NFBC

kohortit (yht noin 30 000 henkilöä)• Hilmo, Avo-hilmo, Kela reseptilääkerekisteri, syöpärekisteri,

kuolinsyyrekisteri• Ei mitään datan tuottoa, käytetään vain olemassa olevaa

dataa• Kaikki fenotyyppejä sisältävä analysointi tehdään

Suomessa, kollaboraattorit saavat ainoastaananalyysituloksia, ei yksilökohtaista tietoa

IPHG-hankkeen kokemuksia

- Innostava pilotti, joka stimuloinut FinnGenin jauusia partnereita (Astra-Zeneca)

- Liian pieni näytekoko - > tarvitaan suurempimateriaali

- Teknistä datan harmonisointia

- KELA tiedot raahaavat auttamattomasti perässä, toivottoman hidasta päivittää tietoja

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N

• Maailmassa lukuisia biopankkeja ja hyviä keräyksiä

• Lukuisat toimijat ovat aloittaneet biopankkien tehokkaan

rakentamisen

• Meillä vahvuuksia, mutta niihin ei voi tuudittautua

• Ministeriöiden vuosien kova työ ja tuoreet poliittiset päätökset

tärkeitä viestejä kansainväliselle kentälle

EMME OLE AINOA MAHDOLLISUUS

T E S T B E D F O R N E X T G E N E R A T I O N R E A S E A R C H & I N N O V A T I O N