Graham Love Chief Executive, Ireland Health

Research Board, Ireland

National perspective Ireland

Whither Personalised

Medicine in Ireland?

Graham Love

Chief Executive

Health Research Board (Ireland)

Presentation to EuroBioForum 2014, Tallinn

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Health Research Board

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• State agency under Department of Health. – Budget €43m, funding portfolio €150 - €200m, staff of 61

• Funding health research. – Infrastructure, capacity building, specific projects.

• Providing evidence for policy. – Public Health Alcohol Bill, Food Pyramid, Fluoridation.

• Information for service planning. – Drug use, disability, mental health.

Personalised Medicine - Care

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Fairly standard, particularly in Cancer.

Oncotype DX Public Usage Oct 2011-Sept 2012 Analysis carried out by GHI and presented at St Gallen 2013

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St Vincents Mater UCHG/ West St James's Waterford Beaumont CUH Midwestern

Patients Tested

Patients Receiving Chemo

Over 4 year clinical trial: €5M saving i.e. €3M in avoided chemotherapy and €2M in free oncotype DX tests for the 690 participating patients.

Personalised Medicine – in future

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• Moving from Personalised Medicine Care

to

Personalised Medicine Research

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Mutation analysis Sequencing

Kinase activation RPPA assays

Copy number analysis SNP arrays

Transcriptomcs Expression arrays

(RNAseq also)

Bioinformatics/Cross ‘omic’ analysis

Target / biomarker validation

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Bio

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Clinical trial in stratified patient population Validated companion diagnostic

Tissue sample collection Tis

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Imp

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Difficult-To-Treat Breast Cancers

Representative cell lines

6 million euro European programme

8 partners (2 SMEs, 6

academic groups)

Project Management:

OncoMark

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+ PI3K

inhibitor Tamoxifen

Placebo Tamoxifen

+

OR

Ductal & lobular Lobular only

Phase II Clinical Trial

n=180 n=110

www.ratherproject.com 11

6 million euro European

programme

10 partners

(4 SMEs, 6 academic groups)

www.angiopredict.com 12

Wagle N et al. Journal of Clinical Oncology (2011)

Before treatment After 15 weeks After 23 weeks

A 38-year-old man with BRAF-mutant

melanoma and subcutaneous

metastatic deposits, treated with Vemurafenib

(BRAF inhibitor)

Predicting Response and Resistance

Approx 50-55k euro/6 months treatment

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RHO-adRP • Inherited form of retinitis pigmentosa

– caused by >150 mutations in the rhodopsin gene

– each affected family has a single dominantly inherited mutation

• Affects ~1 in 30,000 people worldwide

– >30,000 patients in developed economies

• Patients suffer from visual dysfunction losing sight progressively &

completely by middle age

– death of the both rod and cone photoreceptor cells as a consequence

of the processing / translation of faulty rhodopsin

• Treatment options

– no treatments currently available for patients with retained sight

– retinal chips approved in the US for end-stage blind patients

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• Single dose, sub-retinal injection containing two independent

AAV 2/5 vectors encoding:

– RNAi to down-regulate mutant rhodopsin

– replacement rhodopsin gene with a modified nucleotide sequence to

escape suppression & provide functional rhodopsin

• 25+ patents granted across all key territories

– other key IPR licensed from Spark, Benitec (shRNAi) and NIH (AAV)

• US & EU orphan drug designation granted

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GT038 – lead therapeutic

For the treatment of rhodopsin linked autosomal dominant

retinitis pigmentosa (RHO-adRP)

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GT038 – overcomes RHO mutational diversity

RHO-adRP

The challenge: >200 different RHO mutations

adRP patient: single, simple 220μl subretinal injection of

GT038 to the back of the eye

GT038 2 x AAV 2/5 vectors in fixed

proportions containing: RHO RNAi suppression, and an Excess of a special RHO gene

replacement gene

RHO mutant mRNA destroyed RHO replacement survives due to “wobble” at certain 3rd base pairs

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GT038: a unique single solution for RHO-adRP caused by multiple RHO mutations

GT038 Development

• Proof of concept established in mouse and rat models

• Toxicology & biodistribution studies to commence in Q1 2015

• Manufacturing agreements signed with Spark Therapeutics (US) and 1st GLP batches expected in Q12015

• Phase I clinical trial to commence in 2017

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Cardiovascular Disease: sticky platelets?

40 s

120 s

200 s

280 s

360 s

40 s

120 s

200 s

280 s

360 s

CVD Patients Control

Percentage Coverage

Time (sec) Control

Time (sec) Patients

2.5 20 165

5 40 245

10 90 390

15 145 450

Attenuated thrombus formation in CVD patients on Aspirin and

Clopidogrel versus normal controls

Healthy

Control

CVD

Patient

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Economics of Personalised

Health (PH)

• Professor John Forbes

• First HRB Research Leader.

• A scheme to address strategic gaps and leadership capacity in Population Health.

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Economics of Personalised

Health (PH)

• HRB invest €1.4m

over 5 years.

• Look at costs /

benefits of PH.

• Provide reliable

evidence for decision

making around PH.

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Economics of Personalised

Health (PH)

Goal: Develop and

apply empirical

methods for economic

analysis of

personalised health to

support assessment,

regulation and

translation.

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Economics of Personalised

Health (PH)

Potential impact: Raise awareness and develop methods to address the issues associated with using patient information to prevent, diagnose and treat disease or to promote wellness and bridge the gap between research findings and translation into policy/practice.

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Effect of Personalised Health

(PH) on patient outcomes

• Professor Sean

Dineen

• Effect of personalised

clinical information on

outcomes in people

with type 2 diabetes.

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Effect of Personalised Health

(PH) on patient outcomes

• Goal: Establish best level of information to share with patients so they can be more proactive about their care, increase their confidence in managing their diabetes and leads to improvements in their blood sugar control.

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Effect of Personalised Health

(PH) on patient outcomes

• Potential impact:

Personalised health

through increasing the

patients awareness,

knowledge and ability

to make decisions

regarding prevention,

treatment and care

options specifically

selected and targeted

at their risk profiles.

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Moving from Personalised

Medicine Research to Policy

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How did all this happen?

By design?

By accident?

How did it happen?

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• Bottom Up.

• Principal Investigator-driven.

• Personal interest.

• Open funding calls.

How did it happen?

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• There is no ‘top down’ policy position on

Personalised Medicine.

• The funding instruments driving all of this are

NOT Personalised Medicine-specific.

• Which is a great argument for bottom up

funding instruments (creates capacity, starts the

process)…..BUT

How did it happen?

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• The capacity, skills and infrastructure we have

built by the bottom up approach is largely by

accident (or serendipitous design…)

• So, there is a big gap between the Health

Policy layer and the Health Research(Care)

layer in Ireland (& elsewhere?)

How does the Personalise

Medicine Revolution avoid being

a mainly technical one?

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How does the Personalise

Medicine Revolution avoid being

a mainly technical one?

• The gap between the

‘technical world’ and

the ‘policy /

implementation’

world will determine

whether this is a real

revolution like the

Wheel or Fire, or just

a technical one.

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IT: Another ‘technology’ that

transformed the world:

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• Information Technology (IT) took quite a while to

move from the lab to the real world.

• From Turing in the 40s to PCs in the 1980s, it

wasn’t until the 90s that the real IT revolution

took place.

IT: Another ‘technology’ that

transformed the world:

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• Its adoption spread exponentially and drove

massive economic expansion in the 90s.

• The 00s saw this spread to the consumer world

and now it is Business & Consumer:

Everyone/Everywhere!

• Looked at through this lens, Personalised

Medicine has a long way to go…

Whither Personalised Medicine

in Ireland?

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• The key roadblock to large scale adoption

(revolution) is persuading key decision makers

in Public Administration and Business of the

merits & potential of PM.

• We still largely talk an insider’s language.

• 9 out of 10 people probably don’t know what

Personalised Medicine means?

Whither Personalised Medicine

in Ireland?

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• How can you enable a revolution if most people

don’t know what you are talking about?

• A lot more effort is required in ‘making the case’

if this is to happen!

Whither Personalised Medicine

in Ireland?

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• The Solution?

• As a first step: assemble the arguments (with

supporting evidence), in plain language, and

priortise existing resources towards influencing

key decision makers;

– to enable real top-down policy measures targeting

personalised medicine realisation.

– and thus give reality to (..accelerate adoption of)

personalised medicine.