Professor Timothy O’Brien MD, PhD, FRCPI, FRCP,

FACP

Professor of Medicine, NUI Galway

Consultant Endocrinologist, West Northwest Hospital Group

Director of REMEDI and CCMI,

Dean of the College of Medicine, Nursing and Health Sciences, NUI Galway

Research, Clinical Practice and Service Delivery

Conflicts

• Founder, Director and Equity holder in Orbsen Therapeutics

Theme 1

• Ireland working as a single entity can have global impact in clinical translation in defined areas

• Medical Device Technology and Regenerative Medicine

Theme 2

• The needs of the patient always come first

• State of the art clinical care

• Educate health care providers

• Create the clinical care of the future

Theme 3

• Irish healthcare system must contribute to economic recovery through

• Innovation

• Job creation

• Industry engagement

innovation research

Business

Clinic

Innovation

• Definition: something new or different introduced

• From a clinical perspective one might add that it is necessary for the invention to be useful and to represent an advance in clinical practice

• Additionally for the innovation to have impact it must be affordable

• Who should innovate? – all healthcare workers

Innovation will create conflict of interest

• Hospital groups need to have systems to engage with industry

• IP policy – full time hospital staff versus academic clinicians

• COI policy – disclosure and management

• Inventors and innovators should be rewarded

Benefits that academic medicine bring to health service (BMA)

• Critical appraisal

• Financial gains and economic growth

• New ideas, evidence and products

• Better patient care and decreased costs

• Direct benefits to patients treated

• Contribution to high quality clinical services

• Contribution to international health care

Principals underlying academic health science centres (UK Government)

• Excellence in biomedical, clinical, and applied health research

• International standing and critical mass

• Excellence in patient care

• Excellence in education

• Partnerships for delivery benefits in patient care

Expertise - Access to clinical specialists and networks

- Clinical trial management

- Research nursing support

- Biostatistical and methodological support on study design and analysis

- Data management and IT support

Clinical Research Facility

CRFG provides the infrastructure, physical space, facilities, expertise and culture needed to optimally support patient-focused research studies and clinical studies

The CRFG has a very experienced leadership team with extensive international pre-clinical, translational, and clinical research experience allied to global regulatory and reimbursement achievements.

NUI Galway infrastructure

Major priority for enhancing clinical research in Ireland

• Ireland needs to present itself as a single entity for clinical research

• CRFs linked to health care facilities

• Single point of entry for industry

• Distributive model

Distributive Model

• All centres capable of performing high quality clinical research

• Biobanking

• Biometrics

• Education and Competence

• Study management and quality

Regenerative Medicine

• Aims to augment, repair, replace or regenerate organs and tissues that have been damaged by disease, injury or natural aging

• It represents a new paradigm in human health with the potential to resolve unmet medical needs by addressing the underlying causes of disease Alliance for Regenerative Medicine Annual Report 2012-13

New paradigm

• Most therapies today focus on the delay of disease progression and prevention of associated complications

• Regenerative medicine is an interdisciplinary field translating basic science into regenerative technologies

Healthcare Challenges

• Increasing cost ($3 trillion to $6 trillion in the USA over the next 20 years)

• Increasing cost is not only due to technology but is also due to demographics and the aging population

• Increase in chronic disease burden

• Many conditions of unmet medical need

Healthcare Spending

• 75% on chronic diseases

• WHO have defined chronic disease as the priority of the century

• 60% occurs in the last year of life

Aging

• Aging is associated with many degenerative diseases

• Regenerative Medicine has the potential to restore the patient with chronic disease to health

Regenerative Medicine Needs• Advances in fundamental science – multidisciplinary and may

be on the borders of traditional disciplines

• Clinical trials – demonstrate a major clinically meaningful benefit

• Industrialization of product manufacture

• Innovative regulatory strategies

• Innovative business models and re-imbursement strategies

• Demonstrate cost saving through robust health economic analysis

• Investment

Expertise - Cell therapies for vascular and arthritic diseases

- Cell manufacturing and bioprocessing - Medical devices

- Basic stem cell biology - Flow cytometry

- Biomaterials - Immunology

- Translational research - Gene therapy

Infrastructure - Fully Equipped Pre-Clinical Facility

- Centre for Cell Manufacturing Ireland (GMP-compliant cell manufacturing)

- Flow Cytometry Core (Facs Canto and Aria, Guava etc)

- Histology Core

- Microscopy Core (TEM, confocal, etc)

- Tissue Culture Core

- Gene Vector Core

- Clinical Research Facility

Key Research - Patented technologies including novel therapeutics for vascular disease, antibodies for stem cell isolation and devices for stem cell delivery

- Established Orbsen Therapeutics to commercialise REMEDI technology

- Five EU FP7-funded projects

- >550 publications and 25,000 citations since 2004.

The Regenerative Medicine Institute (REMEDI)

Expertise - Adult stem cells, mesenchymal stem cells (MSCs) in particular

- Induced pluripotent stem cells

- Serum-free culture media - Developmental biology

- Regulation and commitment - Stem cell host interactions

Stem Cell Biology

MSC –stimulated cardiac repair

Use of iPSCs in human disease modelling e.g. schizophrenia

Differing osteogenic potential of sorted clones from one cell line

MSCs cultivated in different media. a) 2% FCS media supplemented with EGF and PDGF (b) 10% FCS media supplemented with FGF-2

www.purstem.eu

Expertise - Preclinical models, small and large animal

- Cardiovascular and peripheral vascular disease

- Patented angiogenic molecules

- Patented “next generation” stem cells

- Stem cell homing and tracking

Cell Therapy for Vascular Disease

MSCs increase blood flow in ischemic limbs of diabetic mice

Blood flow restoration

Therapeutic Approach:

MSCs

Porcine acute myocardial infarct

Acute Infarct Region

Diabetic mouse (left) Normal mouse (right)

Expertise - Good manufacturing practice

- Cell processing including isolation, expansion, characterisation

- Clinical trials

- Media formulation

- Cleanrooms

Cell Manufacturing (CCMI)

The CCMI is a versatile cleanroom with standout features including two parallel production suites.  Each of the two suites is capable of clinical grade manufacturing of cellular therapy products and small molecules for therapeutic applications.

CCMI are very interested in discussing opportunities with clients interested in procuring human GMP-grade mesenchymal stem cells or a custom manufacturing service

REMEDI – International Academic Network

Mayo Clinic

Arizona

Cleveland

Georgia Tech

Barcelona

Gustafe-Roussy

LeedsNewcastleEdinburgh Genoa

Toronto

Singapore

Xian

Shanghai

Rotterdam

Israel

Lithuania

published with authors from 197 other institutions worldwidepublished with over 895 authors nationally and internationallypublished with authors from 20 different countries worldwide

REMEDI Investigators have:

“Delivercell”

“Osteocoat”

“Cell Enhance”

“Chondroscaff”

“Angiocell”

“Angiocap”

Orbsen Therapeutics1. Human ORB1+MSC: best-in-class stromal cell purification for therapeutic use – two patents generating over €1M in private equity

• 2. Leveraged private equity to generate €20M in R&D funding from non-exchequer (FP7) sources

• Orbsen - €2.7M from EU FP7 awards; NUI Galway – €2.5 in funding from Orbsen collabtorations Orbsen. Ireland – Over €6.1M to Irish FP7 Partners. EU and USA – Over €20M for all FP7 partners

• 3. Top 15 Irish companies in the EU FP7 : 55% success rate

• 4. Employment for highly-skilled Irish Graduates :Company has grown from 1 FTE to 16 FTE in 18 months. Hired 9 Irish Graduates on 3 year contracts

• 5. The Irish Times InterTradeIreland Innovation Awards 2014 : Short-listed to Top 18 Innovations in Ireland

• 6. Three FP7-funded Clinical trials testing CD362+MSC : 2015 – Phase 1b trial - REDDSTAR FP7; 2016 – Phase 2a trial - MERLIN FP7; 2017 – Phase 1b trial - VISICORT FP7

CURAM

• National Centre for Medical Device Research

Team

IndustryPartners

26 SMEs

3 Start-Ups

13 MNC’s

Research Programme

Trainingand Education

Key Performance Indicators

KPIs

Academic Outputs

Human Capital

CommercialisationNew TreatmentsFunding

Conclusion• Affordable innovation is crucial to contain the

future costs of healthcare

• The focus should be on the development of more effective treatments of chronic and burdensome diseases

• Progress will involve partnership between hospital, academia and industry.

• Ireland should function as a single entity in translational medicine