embargoed till 6pm on fri, 9 nov 2012€¦ · 5. the programme can help to enhance singapore’s...

1

Embargoed till 6pm on Fri, 9 Nov 2012

Press Release

9 Nov 2012

SCIENTISTS AND CLINICIANS COLLABORATE ON 8 PROJECTS TO BETTER

UNDERSTAND AND TREAT DISEASES PREVALENT IN ASIA

Stratified medicine programme: deliver the right therapy to the right patient at the

right time

Eye research: new clinical therapies to cure major eye diseases like glaucoma,

corneal disease.

1. Singapore announces 8 biomedical sciences research programmes1 to advance

understanding and treatment of diseases especially prevalent amongst the Asian population.

These programmes will see biomedical scientists and clinicians working collaboratively to

bring about greater healthcare benefits to society and create economic growth for

Singapore. These programmes were endorsed by the Biomedical Sciences International

Advisory Council chaired by Sir Richard Sykes.

2. Said Mr Lim Chuan Poh, Co-Chair of the Biomedical Sciences Executive

Committee (BMS EXCO) and Chairman of A*STAR, “The collaborations will see a

convergence of talent, capabilities and resources of the basic science and clinical

communities. This augurs well for Singapore as a research hub, as our distinctive value

proposition depends on our ability to coordinate and integrate our research efforts along the

innovation value chain, as well as across multiple research organizations.”

1 Four programmes were awarded under the Strategic Positioning Fund (SPF) while four were

awarded under the Open Collaborative Fund. (See Annex B2)

2

SOME RESEARCH PROGRAMMES

POLARIS

3. Four programmes supported under the A*STAR Biomedical Research Council’s

Strategic Positioning Fund, totalling about $58 million over 3 years, were endorsed by the

BMS IAC. One of the programmes is POLARIS2, which represents a concerted effort by

Singapore to venture into stratified medicine. POLARIS aims to administer the right therapies

to the right patient at the right time. Led by Professor Patrick Tan from the Genome Institute

of Singapore, the programme will leverage on A*STAR’s scientific capabilities to identify new

biomarkers and technologies that can predict how well patients will respond to medical

treatment, as well as how their disease will progress.

4. POLARIS will substantially reduce the cost of healthcare for patients for whom

certain types of medication and treatments are not appropriate, and also reduce the danger

of toxicity arising from consuming medicine that is unsuitable for them. POLARIS will also

work with leading clinicians in the public healthcare institutes to modify existing clinical care

methods and refine stratified healthcare delivery approaches for oncology, eye disease and

other chronic diseases prevalent in Singapore.

5. The programme can help to enhance Singapore’s attractiveness to companies

seeking to develop medical products for the Asian market as they could potentially in-license

promising biomarkers at a more mature stage of clinical validation for product development

and marketing. More information on POLARIS is at Annex A.

6. Said Professor Soo Khee Chee, Deputy Group CEO (Education & Research),

SingHealth, and Director, National Cancer Centre Singapore: “The POLARIS initiative will

help clinicians determine the right diagnosis and treatment for the right patient. One of the

projects we’re embarking on with POLARIS is to identify new biomarkers for lung cancer that

are specific to our Asian population. Lung cancer is among the top three cancers here and is

often difficult to treat. These biomarkers will enable clinicians to better understand patients’

disease and tailor an individual treatment strategy. In addition, with this new knowledge, we

can drive the development of drugs that have greater benefits for our patients.”

2 POLARIS stands for Personalised OMIC Lattice for Advanced Research and Improving Stratification.

3

7. Prof Ng Huck Hui, Executive Director of the Genome Institute of Singapore,

A*STAR, said, “POLARIS is about patient-driven research that will have direct and

immediate impact on patient treatments as well as future impact on the identification of new

biomarkers. Such collaborations with the clinical community allow us to bring our research

expertise and capabilities from the laboratories right into the heart of healthcare for the

benefit of patients and society.”

Genetic Orphan Diseases

8. Another programme, Genetic Orphan Diseases led by Dr Bruno Reversade from

Institute of Medical Biology, aims to study rare genetic diseases in order to better understand

common disease targets and complex disease processes. By identifying mutations in genes

responsible for rare diseases, the researchers will be able to discover key biological

processes which contribute to more common diseases.

9. The Genetic Orphan Diseases programme presents a different and exciting

approach to discovering new cures for common diseases. The three main areas of focus are

skin, cardiovascular, and neurological and cognitive disorders. It has already received strong

interest from scientists, clinicians and drug companies. More information about the

programme is at Annex B1.

Translational and Clinical Research (TCR) Flagship Programme

10. Four TCR Flagship grants administered by the National Medical Research

Council (NMRC) under the Ministry of Health (MOH), amounting to a total of $68 million,

were announced at this year’s BMS IAC. This includes two of the existing Flagship

programmes, in eye diseases and gastric cancer, which received renewed funding of $25

million for a period of five years each.

11. The four TCR Flagship programmes are large-scale “all the way” thematic

programmes spanning basic, translational and clinical research which seek to translate

laboratory discoveries into meaningful applications for patients. Each programme brings

together complementary strengths from across the biomedical research community, to

undertake cutting edge research in diseases of strategic importance to Singapore.

4

12. Mrs Tan Ching Yee, Co-Chair of the BMS EXCO and Permanent Secretary,

Ministry of Health said, “MOH recognises the value that research can bring to addressing

Singapore’s healthcare challenges. These stem from our rapidly ageing population and

changing lifestyles that will see a rise in chronic diseases. I am pleased to note that the TCR

Flagship grants will go a long way to support the good work of our clinician scientists and I

look forward to greater synergy and dynamic and meaningful collaborations among our

healthcare institutions, industry and our partners such as A*STAR.”

$25 million TCR Flagship Programmes

13. The Eye Surgery and Innovative Technologies (EyeSITe) programme is led by

Principal Investigator Professor Donald Tan Tiang Hwee, Medical Director of the Singapore

National Eye Centre and the Singapore Eye Bank, and Professor of Ophthalmology, NUS.

He is also the Chairman of the Singapore Eye Research Institute where the programme is

hosted. EyeSITe aims to provide new clinical therapies to aid in alleviating ocular morbidity

from major eye diseases, including corneal disease, infection, glaucoma, refractive errors

and retinal disorders. Corneal diseases and glaucoma are two of the major causes of

blindness worldwide.

14. This programme builds on the successes of the TRIOS Programme

(Translational Research Innovations in Ocular Surgery) which was awarded a TCR Flagship

grant in 2008. In the course of four years, the team has established five sub-programmes

that have shown promising scientific results, clinical outcomes and commercial potential

which the new programme will be leveraging on.

15. Another programme that received the $25 million TCR Flagship grant is the

Singapore Gastric Cancer Consortium (SGCC) – Redefining the Management of Gastric

Cancer, led by Principal Investigator Associate Professor Yeoh Khay Guan, Dean of the

Yong Loo Lin School of Medicine, National University of Singapore. Gastric (or stomach)

cancer is a leading cause of global cancer mortality, accounting for about 700,000 deaths

worldwide and is particularly prevalent in East Asia and Singapore.

16. Over the past five years, the team has excelled in translating basic science to

clinical research and vice versa. The current award will allow SGCC to transition from a

programme of “Improving Outcomes for Our Patients” to one of “Re-defining the

Management of Gastric Cancer”.

5

$9 million TCR Flagship Programmes

17. In addition to the $25 million programmes, for the first time, NMRC launched

another tier of TCR Flagship grants where two programmes each received $9 million of

funding for a period of five years. The grant recipients are: Genetic Predilection, Epigenetic

Change, MicroRNA Profiling and Experimental Therapies in Heart Failure (Lead Principal

Investigator: Professor Arthur Mark Richards, Director of the Cardiovascular Research

Institute, National University Heart Centre), and Non-Small Cell Lung Cancer: Targeting

Cancer Stem Cell and Drug Resistance (Lead Principal Investigator: Associate Professor

Tan Eng Huat, Senior Consultant, Department of Medical Oncology, and Head, Division of

Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore).

18. More information on NMRC, TCR and the four programmes are at Annex C.

PROGRESS OF BMS EFFORTS

19. The BMS IAC commended Singapore for its BMS efforts in basic research and

TCR in the past 12 years, and lauded Singapore for its efforts on converging its talent, R&D

capabilities and resources for impact.

20. Over the past five years, MOH’s investment in TCR has generated promising

results which have made a positive impact on healthcare. Among these are the development

of innovative treatments and devices such as the world's first robotic flexible endoscopy

system featuring a pair of robotic arms for surgeons to cut away tumours in the digestive

tract by passing them through natural openings such as the mouth. Using this system allows

for surgery which leaves no scars, inflicts lesser pain and facilitates faster recovery.

21. Another example is the development of better ways to stratify dengue patients

by their disease severity, allowing for treatment to be more focused and cost effective, thus

resulting in significant healthcare cost savings. Other studies which have the potential to

significantly improve our understanding of public health have also been launched. These

include a large study investigating how mothers' diet and lifestyle during pregnancy influence

child development, and following on the children’s progress as they grow older. It is one of

the most comprehensive studies of its kind ever done in the world.

6

22. Sir Richard Sykes said, “I have been impressed by how far Singapore has come

in its biomedical sciences journey in all of 12 years. Now that Singapore is in the third phase

of its BMS Initiative with the greater emphasis on convergence for economic and health

outcomes, I believe we can expect to see Singapore attracting more pharma, biologics,

medtech, personal care and nutrition companies here. The attendant social benefits will

come from having early access to cost-effective and novel health solutions.”

23. On a macro level, the BMS Initiative has made significant impact and

contributed much to the economy. The BMS manufacturing output for 2011 was $27 billion.

This was more than four times the output of $6.3 billion when we started in 2000. In terms of

BMS’s share of Singapore’s total manufacturing output, it was nearly 10% in 2011 – an

increase from 4% in 2000. The Compound Annual Growth Rate or CAGR of the BMS output

from 2000 to 2011 was 14%. This reflects the strong and steady growth in this sector. In

2011, BMS also accounts for about 22.4% of the total manufacturing value-added in

Singapore or $12.9 billion in value-added. This was a significant increase from the value

added of $3.8 billion in 2000. Business expenditure on BMS R&D grew to $574m in 2011,

from $47m in 2000.

24. In terms of employment, in 2011, there were over 15,000 people employed in

manufacturing in the BMS sector – more than 2.5 times the number of 6000 employed in

2000. In addition, there were over 5,500 people employed in R&D jobs in the fields of

biomedical and related sciences. Of that number, more than 45% or 2,500 of them had PhDs,

suggesting high value-added jobs were created in this sector.

25. Today, over 100 global biomedical sciences companies, including pharmbio and

non-pharmbio companies, have leveraged Singapore’s world-class manufacturing

capabilities, excellent clinical and scientific infrastructure, connectivity to Asian markets and

pro-business environment to carry out strategic business operations, cutting-edge research

and manufacturing in Singapore. Some of these companies are: Abbott Laboratories, Chugai,

GlaxoSmithKline, Johnson & Johnson, L’Oreal, Novartis, Procter & Gamble and Roche. The

presence of MNCs and their significant investments in R&D are a testimony of the excellent

progress made by Singapore in its BMS thrust. Information on the achievements of BMS

from 2000 – 2012 is at Annex D.

7

___________________________________________________________________

AGENCY FOR SCIENCE TECHNOLOGY AND RESEARCH &

MINISTRY OF HEALTH

For media queries and clarifications, please contact:

A*STAR MOH

Evelyn Ho (Ms)

Deputy Director, Corporate Communications

Agency for Science, Technology and Research

Tel: (+65) 6826 6103

(+65) 9682 6922

Email: [email protected]

Shireen Yeo (Ms)

Assistant Manager, Corporate

Communications

Ministry of Health

Tel: (+65) 6325 1220


Ong Siok Ming (Ms)

Senior Officer, Corporate Communications


Tel: (+65) 6826 6254

(+65) 9733 7434


Poon Jing Ting (Ms)

Assistant Manager, Corporate

Communications

Ministry of Health

Tel: (+65) 6325 1346


Vithya Selvam (Ms)

Senior Officer, Corporate Communications


Tel: (+65) 6826 6291

(+65) 9451 8941


mailto:[email protected]





8

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences and physical sciences and engineering research institutes, and six consortia & centres, located in Biopolis and Fusionopolis as well as their immediate vicinity.

A*STAR supports Singapore's key economic clusters by providing intellectual, human and

industrial capital to its partners in industry. It also supports extramural research in the

universities, and with other local and international partners.

For more information about A*STAR, please visit www.a-star.edu.sg.

http://www.a-star.edu.sg/

9

Annex A

INFORMATION SHEET ON POLARIS INITIATIVE

POLARIS (Personalised OMIC Lattice for Advanced Research and Improving Stratification)

is an initiative within the ambit of stratified medicine, which aims to identify which therapies

are most effective in which patient strata, and to ensure that these appropriate treatments

are administered.

POLARIS will leverage on A*STAR's scientific capabilities to identify new biomarkers and

technologies that can predict how patients would respond to medical treatment, as well as

how their disease would progress. POLARIS will work with leading Singapore clinicians to

modify existing clinical care methods and refine stratified healthcare delivery approaches for

oncology, eye disease, and chronic diseases such as diabetes. It will bring cutting-edge

science such as genomics and metabolomics beyond a research setting and directly into

patient care. This translates to better patient outcomes and a more targeted approach for

treating individuals afflicted by cancer and chronic disease, based on their genetic and

molecular biology profile.

The POLARIS initiative has these distinguishing features that benefit local patients and

patients around the region. It will:

Focus on diseases that are common in Asians or that present differently in Asians.

Integrate scientific research with patient care, leading to discoveries that can be

directly translated into a clinic setting.

Enable collaborations with pharmaceutical companies to design clinical trials and to

develop products stratified for Asian populations.

Who are involved?

The POLARIS initiative is headed by Professor Patrick Tan from the Genome Institute of

Singapore (GIS). His team is made up of basic science researchers from A*STAR (namely

GIS and Bioprocessing Technology Institute (BTI)) and clinical researchers from public

healthcare institutions, including Singapore General Hospital (SGH), National Cancer Centre

Singapore (NCCS), Singapore National Eye Centre (SNEC), and National University Health

System (NUHS).

10

Why is POLARIS necessary?

Impact on healthcare

Patients with diseases such as cancer, heart disease, and diabetes who present similar

clinical features may differ at the genetic or molecular level. These patients experience

different disease progression, and respond differently to the same treatment. By stratifying

patients before treatment, specific therapies can be allocated to those patient sub-groups

that are best predicted to respond well to the treatment, thus leading to better patient

outcomes.

Although there is already considerable local success in the development of new disease

biomarkers and in early phase clinical trials, POLARIS fills a critical gap in translational and

clinical research in Singapore. It stratifies patients for effective and targeted treatment

through the combination of scientific and clinical information specific to each individual.

Impact on economy

Many pharmaceutical companies are increasingly viewing Asia as a major growth area,

especially since there are a variety of diseases common in Asia that are less prevalent in

Western countries, such as gastric cancer, certain lung cancer subtypes, and various

infectious diseases. In addition, for diseases that are common in both Asia and the West,

such as diabetes and heart disease, the treatment required for people in the two regions may

be different due to the subtle genetic differences between populations.

Considering Singapore’s scientific and medical standing internationally, it provides a

compelling proposition for companies seeking to develop medical products for the Asian

market. Besides large pharmaceutical companies, smaller local biotechnology firms will also

benefit from this initiative by having options to in-license promising biomarkers at a more

mature stage of clinical validation for product development and marketing.

How will the researchers conduct the research?

POLARIS is an integrated programme involving scientists and clinicians that seeks to identify

and validate novel biomarkers for specific diseases, which will in turn support clinical

decision-making on which treatment will benefit a patient most – in other words, match the

right patient to the right drug.

11

What POLARIS aims to do

POLARIS aims to:

1. Establish sister CAP3-certified laboratories at SGH and A*STAR, for the development

and validation of OMIC assays.

2. Deploy A*STAR’s technologies and capabilities to support and enhance diagnosis

and management of patients in the clinic.

3. Develop a user-friendly interface to facilitate the clinical and diagnostic application of

scientific data.

Additional Information

POLARIS is one of three complementary initiatives launched by A*STAR. The other two are:

Circulating Tumour Cells (CTCs) project, which aims to develop a new technology to

sieve out cancer cells circulating in the blood, and to analyse them for their potential

to give rise to spread of cancer to other organs (i.e. cancer metastasis). This initiative

is jointly led by Institute of Bioengineering and Nanotechnology (IBN) and Genome

Institute of Singapore (GIS).

Companion Diagnostics in Cancer (CDIC) project, which aims to develop predictive

biomarkers that can help stratify patients for targeted and more effective cancer

treatment. This is led by the Experimental Therapeutics Centre (ETC).

These complementary initiatives enhance the value of POLARIS towards stratifying and

personalising the treatment of cancer and other diseases in our local population. Together,

they have the potential to lead to better patient care, reduce health costs, while at the same

time, have economic value as they support the development of medical products for Asian

populations.

3 The College of American Pathologists (CAP) accreditation is an internationally-recognised and

indicates that a laboratory has met stringent regulatory requirements and achieved high standards of excellence.

12

List of Collaborators

Programme Lead Patrick Tan Boon Ooi

Group Leader, GIS

CO-PI (SGH Lab) Tony Lim Kiat Hon

Consultant, Dept of Pathology, SGH

CO-PI (A*STAR Lab) Christopher Wong Wing Cheong

Chief Scientific Officer, GIS

CO-PI (Bioinformatics and Computation)

Pauline Ng

Group Leader, GIS

CO-PI (Clinical Metabolomics)

Ho Ying Swan

Research Scientist, BTI

Collaborator Disease Champion (Lung Cancer)

Daniel Tan

Associate Consultant, NCCS

Collaborator Disease Champion (GI Cancer)

Iain Beehuat Tan

Associate Consultant, NCCS

Collaborator Disease Champion (Eye Disease)

Aung Tin

Senior Consultant, SNEC

Collaborator (A*STAR Lab)

Liu Jianjun

Deputy Director, GIS

Collaborator (Lung Cancer)

Tan Eng Huat

Senior Consultant, NCCS

Collaborator (GI Cancer) Richard Quek

Senior Consultant, NCCS

Collaborator (GI Cancer) Yong Wei Peng

Senior Consultant, NUH (Through CDIC Initiative)

Collaborator (GI Cancer) Yeoh Khay Guan

Dean, Yong Loo Lin Medical School, NUS

Collaborator (Eye Disease)

Eranga Nishanthie Vithana

Associate Professor, SERI

Collaborator (Breast Cancer)

Goh Boon Cher

Deputy Director, Cancer Sciences Institute of Singapore

Collaborator (Breast Cancer)

Lee Soo Chin

Senior Consultant, National University Cancer Institute Singapore

Collaborator (OMIC Assay Validation)

Evelyn Koay

Director, Molecular Diagnosis Centre, Department of Laboratory Medicine,

NUHS

13

Annex B1

INFORMATION SHEET ON GENETIC ORPHAN DISEASES PROGRAMME

The genetic orphan diseases programme aims to study rare genetic diseases which can lead

to better understanding of common ailments. The team of researchers will identify mutations

in genes responsible for rare diseases so as to gain insights into key biological processes

which underlie common pathologies.

Who are involved?

Led by Dr Bruno Reversade from A*STAR’s Institute of Medical Biology (IMB), this is a

cross-collaborative effort involving research institutes in A*STAR, such as Experimental

Therapeutics Centre (ETC), Institute of Molecular and Cell Biology (IMCB), Singapore

Immunology Network (SIgN) and Translational Laboratory in Genetic Medicine (TLGM).

Middle-east countries as well as industry collaborators such as L’Oreal (Singapore),

AmorePacific (South Korea) and Life Technologies (USA), will also play an integral role in

this programme.

How will the research be carried out?

An extensive network of clinicians will refer patients and families with unique genetic

conditions. The patients’ cells will be bio-banked and used for the development of functional

assays for therapeutic or diagnostic purposes. This bio-bank includes blood cells, skin cells,

as well as induced pluripotent stem cells which have the potential to supply unlimited

numbers of custom-tailored cells to model genetic disorder in vitro.

Genes for the diseases will be identified through next-generation sequencing, a highly-

sensitive tool that detects differences in genes at a genome-wide scale. This is an effective

approach in discovering rare forms of a particular gene that gives rise to observable traits

resulting from a particular rare disorder.

Mutations that are attributed to a particular disease will then be examined in patient’s cells.

With the use of surrogate animal models, the pathogenesis of each disease will also be

interrogated in vivo.

14

Why is this programme necessary?

Many seemingly unrelated genes that underlie similar disorders are in fact functionally

interlinked at the protein level Hence mutations in different genes may result in perturbations

within a network of interacting proteins, leading to the appearance of a common pathology.

Identifying the key protein nodes which act as proxies for frequent pathologies is expected to

yield more relevant therapeutic targets.

The three main areas that this programme will initially focus on are:

- skin disorders

- cardiovascular disorders

- neurological and cognitive disorders

Genetic skin disorders carry a significant healthcare burden. As skin is the most visible and

accessible of the body’s organs, skin conditions can be identified non-invasively and

assessed easily. This allows for the ease of identification of new patients compared to other

disease areas. The findings are of interest not only to the pharmaceutical industry, but also

to the personal care industry.

Rare diseases may also lead to cardiovascular and neurological disorders. There is currently

a substantial gap between the burden of disease for central nervous system (CNS) disorders

and the resources available to manage them. With Singapore’s ageing population, CNS

disorders will become an increasing concern. Research efforts to enhance overall mental

performance as well as to improve the diagnosis, prevention and treatment of these

disorders are hence, important and of commercial interest.

What is the potential impact of the programme?

Rare diseases are currently difficult to treat due to inadequate research and the lack of

known targets for therapy. Advances in science have now made such research possible. In

addition to increasing the understanding of these conditions, the Genetic Orphan Diseases

programme focuses on the linkages between rare and common diseases, to yield new

biomarkers and therapeutic targets. By understanding rare diseases, we are also better able

to understand common diseases without the need for complex and expensive genome-wide

association studies, hence cutting down on time and costs for research. This presents a

different and exciting approach to discovering new cures for common diseases, and has

received strong interests from scientists, clinicians and drug companies.

15

List of Collaborators

PROGRAMME LEAD Bruno Reversade

Senior Principal Investigator, IMB

CO-PIS Birgit Lane

Executive Director, IMB

Brian Burke


Alan Colman


Ray Dunn

Principal Investigator, IMB

Colin Stewart


Byrappa Venkatesh

Research Director, IMCB

Mahmoud Pouladi

Principal Investigator, TLGM

Michael Hayden

Program Director, TLGM

Collaborators Collaborators based in Singapore:

Jeffrey Hill

Head of Biology, ETC

Philip Ingham

Research Director, IMCB

Sudipto Roy

Senior Principal Investigator, IMCB

John Connolly

Principal Investigator, SIgN

Subhra K. Biswas

Principal Investigator, SIgN

Tara-Leah Huber

Asst. Director, Office of Academic Affairs, and Senior Research

16

Scientist, Stem Cell & Developmental Biology, GIS

Poh-San Lai

Principal Investigator & Head of Lab

Division of Human Genetics, Department of Paediatrics

YLL School of Medicine, NUS

Ivy Ng

SingHealth Chief

Chief Executive of KK Women’s and Children’s Hospital

Stuart Cook

Duke-NUS Graduate Medical School, Singapore

Collaborators based overseas:

Hanan Hamamy

Department of Genetic Medicine and Development

Geneva University Hospital

Geneva Foundation for Medical Education & Research

Hülya Kayserili

Medical Genetics Department, Istanbul University

Massoud Houshmand

Special Medical Center, Iran, Tehran

Ariana Kariminejad

Chief Genetic Counselor

Kariminejad-Najmabadi Path. & Genetics Center, Iran

Angus Lamond

Professor of Biochemistry and Director of the Wellcome Trust Centre for Gene Regulation and Expression

College of Life Sciences, University of Dundee, UK

Industry collaborators:

Barry Merriman

Lead System Architect

Advanced Sequencing Genetic Systems, Life Technologies, Inc. USA

Charbel Bouez

Director Advanced Research

L'Oréal Singapore

17

Annex B2

PROGRAMMES AWARDED GRANTS UNDER THE STRATEGIC POSITIONING FUND

Besides POLARIS and Genetic Orphan Diseases, two other programmes have also received

grants from the Strategic Positioning Fund (SPF). They are:

Companion Diagnostics in Cancer programme (CDIC)

Aims to develop predictive biomarkers that can help stratify patients for targeted and more

effective cancer treatment. This is led by the Experimental Therapeutics Centre (ETC).

Characterizing & Tracking Circulating Tumor Cells for Individual Cancer Care

programme

Aims to develop a new technology to sieve out cancer cells circulating in the blood, and to

analyse them for their potential to give rise to spread of cancer to other organs (i.e. cancer

metastasis). This initiative is jointly led by Institute of Bioengineering and Nanotechnology

(IBN) and Genome Institute of Singapore (GIS).

A summary of the grants awarded is given below:

SPF Programme Programme Lead

Host Research Institute

Grant Awarded

1. POLARIS Dr Patrick Tan Genome Institute of Singapore

$20.0 million

2. Characterizing and Tracking Circulating Tumour Cells for Individual Cancer Care

Dr Lim Bing Genome Institute of Singapore (in collaboration with Institute of Bioengineering & Nanotechnology)

$12.3 million

3. Companion Diagnostics in Cancer

Dr Jeffrey Hill Experimental Therapeutics Centre

$13.4 million

4. Genetic Orphan Diseases

Dr Bruno Reversade

Institute of Medical Biology

$12.7 million

TOTAL $58.4 million

18

Annex C

INFORMATION SHEET ON NATIONAL MEDICAL RESEARCH COUNCIL

The National Medical Research Council (NMRC), established under the Ministry of Health in

1994, oversees the developments and advancement of translational and clinical research in

Singapore. It provides competitive research funds to publicly funded healthcare institutions;

awards competitive research funds for programmes and projects, supports the development

of core critical research infrastructure, is responsible for the development of clinician

scientists through awards and fellowships, and fosters interactions and knowledge exchange

among researchers.

In 2006, the Ministry of Health established a new mandate to support translational and

clinical research in areas where Singapore has great potential. With this in mind, NMRC’s

role is ever more important in leading, promoting, coordinating and funding Translational and

Clinical Research in Singapore. NMRC-funded research has led to inter-disciplinary

partnerships and international collaborations, helping to boost the role played by Singapore

biomedical sector on the global stage. Under the Research, Innovation and Enterprise (RIE)

2015 plan, Singapore has earmarked S$16.1 billion over a five-year period (2011-2015) to

fund research and innovation in a variety of sectors, including biomedical and life sciences

research. NMRC is one of the beneficiaries of this boost in funding, reinforcing the Council’s

mandate as the champion for translational and clinical research. Human capital also plays a

key role in the success of Singapore’s translational and clinical research industry.

Since its inception, NMRC has supported over 200 clinicians with scholarships, fellowships

and various talent development awards. The council has also built up the translational and

clinical research capabilities in Singapore through the funding of more than 1,750

competitive research projects and five Translational and Clinical Research Flagship

Programmes. To ensure that its budget is appropriately managed and optimally utilised,

NMRC evaluates the outcomes of the research projects it funds and facilitates the

commercialisation of research findings.

For more information about NMRC, please visit www.nmrc.gov.sg.

http://www.nmrc.gov.sg/

19

INFORMATION SHEET ON TCR FLAGSHIP PROGRAMMES

Title of Programme

Eye Surgery and Innovative Technologies (EyeSITe)

Lead PI Prof Donald TAN Tiang Hwee


Theme

PIs

Prof Roger Wilmer BEUERMAN, Prof AUNG Tin, A/Prof Jodhbir Singh

MEHTA, A/Prof Tina WONG

Amount

Awarded

Tier 2- S$25M

Funding

Duration

Five Years

Background

Corneal diseases and glaucoma are two of the major causes of blindness worldwide. The

disease burden is considerable in Asia, affecting both children and adults alike. An estimated

four to six million patients of infectious keratitis (corneal infections) have gone blind, about 12

million people suffer from corneal opacification, and about 60.5 million people are afflicted

with glaucoma. In 2008, Prof Donald Tan and his team comprising Prof Roger Beuerman,

Prof Aung Tin, A/Prof Jodhbir Mehta and A/Prof Tina Wong, were awarded the TCR Flagship

Programme grant, worth $25m over five years, to run the Translational Research Innovations

in Ocular Surgery (TRIOS) programme.

Achievements

In four years, the team has established five programmes that show promising scientific

results, clinical outcomes and commercial potential. Notable achievements include:

Invention of the “Tan EndoGlide”

- A disposable surgical device and the first device marketed in the world with Food and Drug

Administration (FDA) and Communauté Européenne approval for selective tissue

transplantation of the cornea. It demonstrated less damage caused to vital corneal

endothelial cells during Endothelial Keratoplasty (EK) surgery or Descemets Stripping

Automated Endothelial Keratoplasty (DSAEK), a new form of suture less, keyhole corneal

transplantation, using the endoglide. Patients in Singapore had first access to the device in

2009. Currently, the device is used at the Singapore National Eye Centre (SNEC) for all

patients undergoing the new corneal transplant procedure that is rapidly replacing

20

conventional forms of corneal transplantation. SNEC is now one of the leading centres

worldwide for such procedures.

- EndoGlide 2 (enhanced EndoGlide 1) was released in September 2012. It aids the surgeon

in donor tissue placement into the glide and for use with ultrathin donor tissue that has been

shown to provide faster visual recovery. The team has now patented the Tan EndoGlide 3,

which would be a new version for the latest form of corneal transplantation i.e. Descemets

Membrane Endothelial Keratoplasty (DMEK). DMEK is the most recent form of EK surgery,

whereby only Descemets membrane (DM) containing the endothelial monolayer of cells is

stripped from the donor cornea, and inserted into the recipient cornea. Although DMEK

surgery is still at an experimental stage, a licensing agreement with Network Medical has

already been achieved. The team is currently unaware of any competing DMEK insertion

device in existence; it is the hope that the Singapore Eye Research Institute (SERI) TRIOS

will be the first to lead the field here. The team further hopes to manufacture the EndoGlide 3

in Singapore.

Defensins

This new generation of natural antibiotics has the potential to relieve the enormous burden of

ocular morbidity due to infections from bacteria and fungus that is seen throughout South

East Asia, as well as in the US and Europe. Defensins also show significant potential as a

new class of antimicrobials in other fields of medical therapeutics such as systemic infections

as a viable alternative to vancomycin for Methicillin-resistant Staphylococcus Aureus (MRSA),

a type of Staphylococcus bacteria resistant to certain antibiotics, infections, as well as in

applications such as the disinfective systems required in the cosmetics industry. The team is

now testing their new Defensins in cell culture studies to assess its ability to kill bacteria,

fungi and viruses in the lab and in animal eyes, with the ultimate aim to develop eye drop

formulations for human clinical trials to prevent infection and scarring in the eye.

The three novel synthetic defensin molecules developed are:

(i) Broad spectrum antibiotic with excellent biocompatibility and effectiveness against gram

positive and gram negative bacteria as well as fungus. It is safe to the eye, not susceptible to

developing resistance and does not inhibit corneal wound healing.

(ii) Antifungal with excellent killing against fungus (within 15 to 30min) and yeast.

(iii) Modified natural product that is highly effective against all gram positive organisms and

especially MRSA.

21

Ocular Drug Delivery System

A novel drug delivery system utilising advanced nanotechnology and biomaterials that allows

for timed-release of drugs to treat eye conditions. In collaboration with the School of

Materials Science and Engineering at NTU, novel nano-drug carriers are bioengineered to

deliver high concentrations of drugs over a sustained period of time via sustained release

formulations. For instance, the team has successfully developed a sustained drug delivery

formulation using a unique combination of nanoliposomes with Latanoprost (LipoLat), for

lowering the intraocular pressure in glaucoma. A first in man Phase1/2 study on LipoLat is

expected at the end of November 2012, at the SNEC on patients who suffer from ocular

hypertension and primary open angle glaucoma.

The novel carrier systems have now been shown to enable a steady release of the drug over

several weeks. Such early outcomes seem to indicate its great potential as the next

generation of ocular drug delivery systems for all other ocular diseases, thus eliminating the

need for frequent and long-term eye drops to control such conditions. Patients are therefore

freed from the requirement to administer frequent, daily eyedrops for years on end, a

requirement which often may last for a lifetime and result in non-compliance, can cease to

carry multiple bottles of eyedrops, and potentially face reduced risk of disease progression.

Overall, there is a notably improved quality of life.

Femtosecond lasers in corneal surgery

Two major outcomes were:

a) The establishment of a new surgical procedure i.e. Refractive Lenticule Extraction

(ReLEx), a new alternative to LASIK surgery.

Clinical trials are confirming that ReLEx SMILE (SMall Incision Lenticular Extraction) laser

treatment is highly effective and potentially safer than LASIK as there is no flap made on the

cornea. Unlike LASIK, which uses two lasers and vaporises the corneal tissue to correct

vision, ReLEx SMILE uses only one laser for the entire procedure and removes only an inner

lens-shaped piece of cornea which corresponds to the patient's myopia and/or astigmatism,

through a keyhole incision in the cornea.

b) Exploring a biological solution for Presbyopia via corneal lenticule re-implantation

following cryopreservation

22

Refractive lenticule from the ReLEx SMILE procedure have demonstrated that they can be

cryopreserved and stored indefinitely. They have further shown in animal models that they

can be re-implanted back into the cornea with retention of biological viability.

SERI has filed a patent for this technology, a potentially reversible procedure that is the

first of its kind, which adds a significant safety factor to laser corneal surgery. Similar to the

concept of cord blood banking, the lenticules can be stored for the same patient, or can even

be donated to other patients who require some forms of corneal transplant surgery. The

TRIOS program also aims to refashion these lenticules to treat presbyopia ("lau hua"),

which occurs in every person, and for which there is no treatment other than reading glasses.

This technology is due to be licensed to a new spin-off company, called Lenticor, which will

have the rights for this technology for the region. Lenticor will be a new local start up

company that has prior expertise in cryopreservation and private cord blood banking. It will

be able to offer patients undergoing ReLEx SMILE laser surgery the option of storing their

own lenticules for future use. Working with A*STAR's Exploit Technologies that is helping out

with TRIOS commercialisation, the final licensing agreement is expected to be signed with

Lenticor within the next few days, and this will be a true validation of the translational bench

to bedside success of TRIOS. TRIOS SERI scientists and clinician researchers at SNEC will

continue to work closely with Lenticor in a research collaboration to use this technology in

developing new treatments for corneal transplants and for the treatment of presbyopia.

Discovery of genes linked to Primary Angle Closure Glaucoma (PACG)

Through an international consortium led by the team as well as inter-disciplinary

collaborations established with local institutions such as the Genome Institute of Singapore

(GIS), National University of Singapore (NUS) and Tan Tock Seng Hospital, a genome-wide

association study (GWAS) identifed three new susceptibility loci for Primary Angle Closure

Glaucoma (PACG). Published in the Aug 2012 edition of high IF journal, Nature Genetics,

this discovery will lead to further research to elucidate the full genetic architecture of PACG,

eventually allowing the development of a clinically useful genetic profile for the identification,

risk stratification and thus treatment of PACG patients in the future.

Details of the Study

The new programme “Eye Surgery and Innovative Technologies (EyeSITe)” will leverage on

their past success with the aim to provide new clinical therapies diagnostic applications to aid

23

in alleviating ocular morbidity from major eye diseases, including corneal disease, infection,

glaucoma, refractive errors and retinal disorders. The specific objectives are:

1) The development of new classes of antimicrobial small peptide and peptoid molecules

which will have a significant impact in treating corneal infections caused by Gram-negative,

Gram-positive bacteria, as well as fungal infections and also for systemic infections.

2) The development of sustained drug delivery carriers to provide effective prolonged drug

release without relying on patient compliance would improve therapeutic outcomes and

overall healthcare and disease management in these patients who are generally elderly. This

technology can clearly be applied across other ophthalmic conditions which require chronic

medical treatment.

3) The bionic cornea programme aims to develop a carbon-fibre and titanium-based Artificial

Cornea to treat severe corneal blindness. Other aims include the growing of corneal cells in

the laboratory as a substitute for corneal transplantation, and developing new medical

devices for transplantation surgery.

4) The femtosecond laser programme aims to provide a new treatment for keratectasia and

keratoconus, and for presbyopia, and to develop new forms of cataract surgery with

femtosecond lasers for Asian eyes which may provide more precise and safer clinical

outcomes.

5) The PACG programme aims to develop new diagnostic and prognostic approaches to

PACG, with a potential novel risk prediction algorithm combining ocular imaging and genetic

markers to detect high risk patients (stratified medicine), which if successful, will be

applicable not only in the clinic, but also at a population-wide level. In addition, the

programme will provide new insights into the genetic basis of PACG as well as anatomical

and physiological basis of angle closure, which in turn will lead to more targeted approaches

to treating this blinding condition. As a first step towards this, the Singapore team has

discovered the first three novel genetic loci associated with PACG. This information on the

genes involved in PACG has now opened up new and exciting research areas that have the

potential to culminate in new treatment modalities for angle closure glaucoma in the future.

24

These programmes, if successful, will result in better health outcomes for the above-

mentioned ocular conditions, improve medical practice, and may also provide significant

economic outcomes to Singapore.

TEAM’S PROFILE

Donald TAN Tiang Hwee (LEAD PI)

Medical Director, Singapore National Eye Centre (SNEC)

Chairman, Singapore Eye Research Institute (SERI)

Professor, Dept. of Ophthalmology, National University of Singapore (NUS)

Chair, Eye Academic Clinical Programme, Duke-NUS Graduate Medical School

Medical Director, Singapore Eye Bank

Involved primarily in clinical and translational research in cornea, refractive surgery and

myopia, he has published over 300 peer-reviewed articles (h index = 42), contributed 18

book chapters and holds 13 patents in stem cell culture, myopia prevention, refractive

corneal implants and surgical devices for endothelial keratoplasty, and has also trained 22

corneal fellows from 13 countries. He is the recipient of over 20 awards, which include the

APAO 2001 De Ocampo Award, the AAO 2006 Distinguished Achievement Award, the

ISRS/AAO 2009 Casebeer Award, the Saudi Ophthalmological Society 2010 Gold Medal,

the Australia and New Zealand Corneal Society 2011 Doug Coster Award, the Canadian

Society of Ophthalmology 2011 W. Bruce Jackson Award, the EuCornea 2012 Medal, and

the Portland, Oregon Arthur Devers 2012 Lecture.

Prof Tan established the Asia Cornea Society in 2007 and the Association of Eye Banks of

Asia in 2009, and is currently President of both societies. In 2012, he assumed the

Presidency of the US based Cornea Society, its first International President.

AUNG Tin

Senior Consultant & Head of Glaucoma Service, Singapore National Eye Centre (SNEC)

Deputy Executive Director, Singapore Eye Research Institute (SERI)

Professor, Dept. of Ophthalmology, National University of Singapore

Prof Aung is a pre-eminent clinician-scientist and his research interests are angle closure

glaucoma and the molecular genetics of eye diseases. Prof Aung and his team were the

first in the world to discover the SLC4A11 gene responsible for Congenital Hereditary

Endothelial Dystrophy (CHED), published in Nature Genetics. Recently Prof Aung and his

25

team were the first to study PACG genetics using a genome-wide perspective and results

were published in the prestigious scientific journal, Nature Genetics, on 26 August 2012.

This was a major achievement for the Singapore team, which led the largest international

consortium of doctors and scientists involved in glaucoma research.

Prof Aung has more than 300 publications, has been an Invited Lecturer to more than 80

International Conferences in 30 different countries and has received numerous awards

including the Singapore NMRC-BMRC Clinician Scientist Awards in 2005 and 2008, the

Nakajima Award from the Asia Pacific Academy of Ophthalmology in 2006 and the

Singapore President’s Science Award in 2009. Prof Aung has been awarded more than

US$15 million in research grant funding and has set up collaborations with many centres

worldwide in the US, UK, India, China, Myanmar, Thailand, Indonesia and Japan. Prof Aung

is a member of the Editorial Board of the following journals: Ophthalmology, Eye, Journal of

Glaucoma, International Glaucoma Review and Asian Journal of Ophthalmology.

Roger Wilmer BEUERMAN

Senior Scientific Director, Singapore Eye Research Institute (SERI)

Professor, Duke-NUS, SRP, Neuroscience and Behavioural Disorders

Director, Singhealth Medical Proteomics Centre

Prof Roger Beuerman is adjunct Professor of Ophthalmology, Yong Loo Lin at NUS, School

of Medicine; Adjunct Professor of Chemical and Biomedical Engineering at NTU; and

Adjunct Senior Scientist at the Bioinformatics Institute. He is a clinical scientist with more

than 25 years of experience in ophthalmology research working on the development of

refractive surgical procedures, corneal preservation medium, the clinical confocal

microscope used in ophthalmology, biomarkers of eye disease and peptide based anti-

microbials.

He is an expert in epithelial wound healing and internationally known in the area of ocular

surface disease. He is developing new antimicrobial peptides for topical applications, and in

ocular proteomics he has developed new biomarkers focusing on the diagnosis of dry eye

and inflammation. He has co-edited three books in ophthalmology, the latest on myopia.

Overall, he has more than 220 publications, sits on several editorial boards, such as

“Cornea” and “Ocular Surface” and reviews grants for the SingHealth Foundation, the

National Medical Research Council and is on the Association for Research in Vision and

Ophthalmology (ARVO) Program Planning Committee. Prof Beuerman was recently made a

26

Fellow of ARVO and has received the 2009 President’s Award in Science and Technology.

Jodhbir Singh MEHTA

Co-Head, Cornea and External Disease, and Senior Consultant, Singapore National Eye

Centre (SNEC)

Head, Tissue Engineering and Stem Cell group, Singapore Eye Research Institute (SERI)

A/Prof Jod S Mehta joined the SERI faculty as a Clinician Scientist and is also a Consultant

Ophthalmologist at SNEC since 2008. He has academic affiliations with DUKE-NUS

Graduate Medical School and is also an Adjunct Associate Professor with NUS. Dr Mehta

received his general ophthalmic training at Moorfields Eye Hospital, London. He also

completed a Corneal External disease and Refractive fellowship with Moorfields and SNEC.

He has won awards at the American Academy of Ophthalmology (AAO), ARVO and

recently the Nakajima Award at theAsia Pacific Academy of Ophthalmology.

His corneal interests lie in corneal transplantation – penetrating keratoplasty, lamellar

keratoplasty and endothelial keratoplasty, femtosecond laser technology, corneal imaging,

corneal infections, corneal refractive surgery, keratoprosthesis surgery, ocular drug delivery

systems and corneal genetics. Dr Mehta is author of over 140 peer-reviewed publications,

seven book chapters and six patents.

Tina WONG

Senior Consultant, Glaucoma Service, Singapore National Eye Centre (SNEC)

Head, Ocular Therapeutics and Drug Delivery Research Group, Singapore Eye Research

Institute (SERI)

A/Prof Tina Wong holds an adjunct faculty position at the School of Materials Science and

Engineering, NTU. Previously, A/Prof Wong was a Glaucoma Fellow at Moorfields Eye

Hospital in London, UK, where she completed her general Ophthalmic training. She was

awarded the highly competitive Wellcome Trust Vision Research Fellowship in 1999 for

which she completed a PhD on “The role of matrix metalloproteinases in conjunctival wound

healing” at the Institute of Ophthalmology, University College London in the laboratory of

Prof Peng T. Khaw. Her research resulted in her receiving several national prestigious

awards.

27

Title of Programme

Singapore Gastric Cancer Consortium – Re-defining the Management of Gastric Cancer

Lead PI A/Prof YEOH Khay Guan


Theme

PIs

Prof Patrick TAN, Prof Yoshiaki ITO, Dr YONG Wei Peng

Amount

Awarded

Tier 2- S$25M

Funding

Duration

Five Years

Background

Gastric adenocarcinoma, or gastric cancer, is a leading cause of global cancer mortality that

accounts for 700,000 deaths worldwide annually. It is particularly common in East Asia

countries such as China and Korea, as well as in Singapore where males have a 1.50

lifetime risk for it. Prevention, including early detection, and treatment options for the disease

are clinically challenged at present. For most countries, screening efforts are directed

towards population subgroups that are at highest risk of developing gastric cancer because it

is not practical to carry out mass population screening programmes which are cost-effective

in Japan and South Korea where incidences of gastric cancer are comparatively higher. In

terms of treatment, surgery, chemotherapy and targeted therapies- newer treatment option

which uses small molecules and antibodies to inhibit the pathways of specific oncogenes

(genes that potentially cause cell to turn cancerous)- have not been highly effective as they

yield varying responses in patients.

In 2007, a national translational research group of clinicians and scientists from universities,

research institutes and hospitals across Singapore working in gastric cancer research, the

Singapore Gastric Cancer Consortium (SGCC), was the awarded the TCR Flagship

Programme to solve important clinical questions to improve the care of gastric cancer

patients. Since the group’s inception in 2006, it has grown to comprise more than 31

members, led by A/Prof Yeoh Khay Guan and the theme PIs A/Prof Patrick Tan, Prof

Yoshiaki Ito, and Dr Yong Wei Peng who form the group’s steering committee.

The current award will be a continuum for SGCC to transit from “Improving Outcomes for Our

Patients” to “Re-defining the Management of Gastric Cancer”. Over the past five years, the

team has excelled in translating basic research to clinical research and vice versa. Notable

achievements that will cast positive impacts in future healthcare for gastric cancer includes

28

robotic endoscopy, genomic-guided personalised treatment that yields better patient

response and decreased drug toxicity, early detection of gastric cancer in clinical settings

through diagnostic kits, and improved therapeutic strategies.

Notable Achievements

- New genomic classification of gastric cancer (published) that may be superior to the classic

Lauren classification. It is the basis for genomic-guided personalised treatment (undergoing

prospective proof-of-concept (POC) international clinical trial; as of Oct 2012, a total of 50

patients have been recruited) with the aim of achieving improved patient response rate and

decreased drug toxicity.

- Robot endoscope system – first group in the world to perform robotic Natural Orifice

Transluminal Endoscopic Surgery (NOTES) in human patients (2011). This work recently

received the President's Technology Award and has led to a spin-off company (EndoMaster

Pte Ltd).

- First in Singapore to diagnose early stage 1 or stage 0 gastric cancer through endoscopic

screening of a pre-disease high risk cohort (Gastric Cancer Epidemiology Programme,

GCEP cohort comprising 3,000 subjects). From this cohort, 17 patients were detected with

early cancers.

- Publications being prepared for (1) whole-genome sequencing project completed in 2011 in

collaboration with GIS, and (2) for key genetic changes identified in early stage (I & II) gastric

cancer completed in collaboration with Illumina.

- Biomarker discovery projects have resulted in the protection of two novel biomarkers for

gastric cancer detection. A commercialisation grant was secured to produce novel reagents

(aptamers, monoclonal antibodies or peptides) against one of these biomarkers, C9, and the

team is in the process of developing a diagnostic kit for clinical applications.

- In the reportedly largest study of genomic copy number alternations in gastric cancer to

identify novel drug targets, results indicate that close to 37% of the gastric cancer cases

diagnosed may be treatable by drugs targeting a single cell signaling pathway. For one of

these targets (FGFR2), we found that FGFR2-amplified gastric cancers exhibited sensitivity

to dovitinib, an orally bioavailable targeted therapy. These findings were translated into a

first-in-man industry supported clinical trial in Singapore.

29

- Deepened understanding of molecular pathways leading to gastric cancer development:

found two genes, FAT4 and ARID1A to be mutated in 5% and 8% of stomach cancers,

respectively. Functional experiments demonstrated that disrupting the activity of FAT4 and

ARID1A is likely important for gastric cancer to develop.

- Discovered a way to overcome resistance to cisplatin, a commonly used chemotherapeutic

agent: target BMP4 (Bone morphogenetic protein 4) as a promising therapeutic strategy for

improving the efficacy of cisplatin treatment.


In this new five-year run, the programme will maintain its focus, with expanded scope on:

(i) EARLY DETECTION- as the principle strategy to improve gastric cancer clinical

outcomes.

The theme will be led by A/Prof Yeoh (lead PI) and supported by Prof Patrick Tan, to identify

suitable blood-based diagnostic biomarkers, from candidate biomarkers identified in a

previously assembled pre-disease high-risk cohort (Gastric Cancer Epidemiology

Programme, GCEP), to develop a cost-effective screening strategy for Singapore patients.

(ii) THERAPEUTICS- to improve treatment.

The theme will be led by Dr Yong Wei Peng, supported by Prof Patrick Tan, to firmly

establish the clinical usefulness of the genomic classification of gastric cancer previously

discovered by the team to be able to predict patient survival and drug responses in cell lines

and patients, through an ongoing prospective clinical trials, as well as to test the efficacy of

new treatment options, e.g. peptide vaccines, through new clinical trials.

(iii) GASTRIC CARCINOGENESIS- to understand the molecular biology of gastric cancer.

The theme will be led by Prof Yoshiaki Ito, supported by Prof Patrick Tan to identify new

therapeutic targets and early detection biomarkers, through the use of animal models that

faithfully recapitulate various aspects of gastric cancer development including transitions

from normal gastric tissue, to precancerous states and eventual cancer.

30

TEAM’S PROFILE

YEOH Khay-Guan (LEAD PI)

Associate Professor of Medicine

Yong Loo Lin School of Medicine

National University of Singapore

Dr Yeoh is a clinician-investigator and gastroenterologist at the National University Hospital,

Singapore. His research interest is in the early detection of gastric and colorectal cancers by

screening and the use of molecular markers. He is the Lead-Principal Investigator for the

Singapore Gastric Cancer Consortium, a national translational-clinical research programme

focused on improving outcomes for gastric cancer.

He has published over 100 peer-reviewed papers in international journals. Dr Yeoh serves

in several leadership roles including Dean in the Yong Loo Lin School of Medicine. He also

chairs the National Colorectal Cancer Screening Committee of the Health Promotion Board,

Ministry of Health which recommends guidelines for the national colorectal screening

programme in Singapore.

Patrick TAN

Professor, Duke-NUS Graduate Medical School

Group Leader, Genome Institute of Singapore (GIS)

Program Leader, Cancer Science Institute of Singapore

Research Associate Professor, Institute of Genome Sciences and Policy, Duke University

Dr Patrick Tan holds a joint appointment as a Professor at the Duke-NUS Graduate Medical

School and a Group Leader at GIS. He is a Program Leader in Genomic Oncology at the

Cancer Science Institute of Singapore, National University of Singapore and a Research

Associate Professor in the Institute of Genome Sciences and Policy at Duke University,

USA.

His research focuses on the application of genomics to cancer and infectious disease. He

received his B.A. (summa cum laude) from Harvard University and MD PhD degree from

Stanford University, where he received the Charles Yanofsky prize for Most Outstanding

Graduate Thesis in Physics, Biology or Chemistry. Locally, he has received the President’s

Scholarship, Loke Cheng Kim foundation scholarship, Young Scientist Award (A-STAR),

Singapore Youth Award (twice), and the Singhealth Investigator Excellence Award.

31

Yoshiaki ITO

Programme Leader and Senior Principal Investigator, Cancer Science Institute Singapore


Yong Loo Lin Professor of Medical Oncology

Department of Medicine, Yong Loo Lin School of Medicine,


Prof Ito obtained his MD PhD from Tohoku University, Japan, and studied in Duke

University, USA, Imperial Cancer Research Fund Laboratories, UK and National Cancer

Institute, USA. He became a Professor in 1984 at the Institute for Virus Research, Kyoto

University, and served as Director between 1995 and 2001. His area of research is in the

elucidation of the molecular mechanism of carcinogenesis. He discovered the major

oncoprotein of polyomavirus, middle T antigen that triggered the discovery of well known

tumor suppressor, p53.

More recently, he discovered the RUNX family of genes which are critical regulators of

developmental and cancer. In particular, he discovered RUNX3 is a tumor suppressor of

gastric, colon and many other solid tumors.

YONG Wei-Peng

Senior Consultant

Department of Haematology-Oncology

National University Cancer Institute, Singapore (NCIS)

Dr Yong obtained his medical degree and postgraduate training from the University of

Aberdeen, Scotland. After completing an oncology fellowship at the National University

Hospital, he was awarded the A*STAR international clinical pharmacology fellowship at the

University of Chicago. His clinical interest is in gastrointestinal cancers and his research

interests are pharmacogenetics and epigenetics in cancer.

32

Title of Programme

Genetic Predilection, Epigenetic Change, MicroRNA Profiling and Experimental Therapies

in Heart Failure

Lead PI Prof Arthur Mark RICHARDS


Theme

PIs

A/Prof LIU Jianjun, Prof Kandiah JEYASEELAN, Prof Colin Lawson

STEWART

Amount

Awarded

Tier 1- S$9M

Funding

Duration

Five Years

Objective of the Study

To improve understanding of inherited factors for risk of heart failure, through genetic studies

and the identification of specific gene products, with a view to improving prediction of heart

failure and identifying new treatments.


Heart failure is the final common pathway of a myriad of cardiovascular diseases. It is a

major health problem worldwide and is projected to afflict one in five people now in middle

age at some point in time in their remaining lifetime. According to the World Health

Organisation (WHO), the largest increase in incidences of cardiovascular disease is

reportedly seen in Asia. While this is in part due to rising rates of smoking, obesity,

dyslipedemia and diabetes, the global shift in the burden of heart failure to the developing

countries of Asia suggests that ethnicity is related to differences in the incidence and

outcome of heart failure observed in multi-racial Asia.

For Singapore, heart failure is the most common cardiac cause of hospitalisation, with only

32% of cases surviving five years. About 30% to 50% of heart failure patients have small,

stiff hearts that are not dilated, can still pump with reasonable strength, but fill poorly (heart

failure with preserved ejection fraction where ejection fraction refers to the fraction of blood

pumped from the heart with each heartbeat) while the remaining have enlarged hearts that

pump weakly (heart failure with reduced ejection fraction). There appears to be no difference

in background factors (high blood pressure, coronary artery disease, diabetes and

cholesterol) detected for both types of heart failure. However, inherited factors, specifically

genetic variants, are postulated to be associated with the type of heart failure developed.

33

Awarded the National Medical Research Council’s (NMRC) first Tier 1 grant to run a TCR

Flagship Programme, the research team, led by Prof Mark Richards and comprising co-PIs

A/Prof Liu Jian Jun, Prof Kandiah Jeyaseelan, and Prof Colin Stewart, brings together

essential skills and experience in both basic science and clinical care of heart failure from

team members based in four sites – the National University Heart Centre, Singapore

(NUHCS), the Genome Institute of Singapore (GIS), the faculty of Biochemistry, Yong Loo

Lin School of Medicine and the Institute of Medical Biology (IMB).

Prof Richards is the director of the Cardiovascular Research Institute (CVRI) at NUHCS. He

has over 25 years of experience in clinical care for heart failure patients in New Zealand, and

many years of research experience, alongside basic scientists, investigating new

biochemical pathways in heart failure. His work has led to the establishment of new blood

tests for diagnosing and monitoring heart failure which have improved care and survival in

this condition. Under his oversight, the co-PIs, as experts of their respective research domain,

will be leading investigations focused upon (i) differences in genetic backgrounds, (ii)

different activation and de-activation of genes (“epigenetics”), (iii) the role of intermediate

gene products (“microRNAs”) and the (iv) potential of gene targets, to improve understanding

of inherited factors for risk of heart failure so that the overall aims of improving prediction and

progression of heart failure and identifying new treatments can be fulfilled.

Specifically, cardiac ultrasound scans will be used to measure changes in heart function to

determine any relation to genetic variation. The team will also explore the use of microRNAs

that are detected circulating freely in the blood of patients with heart failure or afflicted with

heart valve disease and heart attacks, as potential biomarkers for the diagnosis of heart

failure and as pointers to new therapeutic targets in heart failure. Animal studies using mice

with genetic modifications which lead to heart failure or after experimental induction of heart

failure will be conducted in parallel to human studies. Corroboration of findings from both

subject groups opens up the plausibility of using genetically engineered mice to find new

treatments for heart failure at the first instance.

In this run of the grant, Prof Richards will also be joined by internationally experienced

clinical colleagues from NUHCS, namely A/Prof Carolyn Lam, A/Prof Ling Lieng His and Dr

Mark Chan. They will be providing essential input into management of patients with heart

failure and serious heart valve disease and coronary artery disease. Dr Roger Foo, who has

over 15 years of experience in the UK and recently joined CVRI, will be sharing his special

34

knowledge in the epigenetics of human heart failure to potentially develop gene-targeted

treatments.

TEAM’S PROFILE

Arthur Mark RICHARDS (LEAD PI)

Professor in Medicine, National University of Singapore (NUS)

Director, Cardiovascular Research Institute (CVRI)

National University Heart Centre, Singapore (NUHCS)

National University Health System (NUHS)

Prof Mark Richards graduated from the University of Otago, New Zealand, and was trained

in cardiology in both New Zealand and the United Kingdom. He has directed NUHC’s CVRI

since October 2009. He has held clinical responsibilities in Cardiology for over 25 years and

for many years has also worked alongside basic scientists in researching new biochemical

pathways in heart failure. He established the Christchurch Cardioendocrine Research

Group (now Christchurch Heart Institute) which has conducted integrated research into the

pathophysiology, diagnostics and therapeutics of cardiovascular disease in the four

disciplines of clinical observational and therapeutic trials, molecular biology, pre-clinical

physiology (models of heart failure) and biomarker discovery and immunoassay.

His group contributed original work on the role and application of circulating vasoactive

peptides and in particular was the world’s foremost pioneering group in elucidating the

bioactivity of the cardiac natriuretic peptides and applying measurement of plasma cardiac

peptide levels as diagnostic and prognostic tests in heart failure. The improved

understanding of heart failure from Prof Richards and his team has led to the establishment

of new blood tests for diagnosing and monitoring heart failure which have improved care

and survival in this condition. Prof Richards will work alongside eminent researchers with

expertise in the genetic and epigenetic aspects of cardiovascular disease.

LIU Jianjun

Deputy Director

Senior Group Leader, Human Genetics

Genome Institute of Singapore (GIS)

Dr Liu Jianjun obtained a PhD in Quantitative Genetics from Duke University in the US, and

has held scientific appointments in New York and subsequently in Singapore, with positions

held in NUS, NTU and GIS over the last 10 years. He has carried out a series of genome-

35

wide association study (GWAS) studies in Chinese populations and identified susceptibility

loci for a range of infectious and autoimmune diseases. There is value in the GWAS data

collected from an Asian population in helping to understand the genetic heterogeneity of

disease susceptibility between Asian and European populations. In addition, he has a

powerful track record in cancer genetics, e.g. nasopharyngeal carcinoma and non-Hodgkin

lymphoma, and in particular breast cancer.

As a member of the Breast Cancer Association Consortium (BCAC), his group worked on

the first GWAS study on breast cancer, which identified five common susceptibility loci for

breast cancer. Other areas of research include neurological and neuropsychiatric disorders

such as stroke, Parkinson’s Disease (PD), Schizophrenia and related psychoses. His team

discovered that genetic variation of the LRRK2 gene influences the risk for PD in Asian

populations but the mutation spectrum of LRRK2 is different between Asian and European

patients. G2385R was identified as a common risk mutation in Asian populations, but

absent in European population.

Dr Liu and his team will now direct their expertise at genetic variation influencing onset and

evolution of heart failure.

Kandiah JEYASEELAN

Professor in Biochemistry and Molecular Biology

Department of Biochemistry, Yong Loo Lin School of Medicine,


Genetic engineering, especially gene cloning and expression has been the passionate area

of research for Prof Kandiah Jeyaseelan. Prof Jeyaseelan obtained his PhD and DSc in

Molecular Biology from the University of Sheffield, England. He is also a Chartered Biologist

and a Fellow of the Society of Biology (FSB), London. As a pioneer molecular biologist in

Singapore since 1984, he has published many international research articles and conducted

workshops and scientific meetings on molecular biology and biochemistry. In the early 90’s

his laboratory at NUS was the first to clone a cardiotoxin gene. His ability to keep abreast

with the advancement in molecular genetics has enabled him to carve a niche area of

research; RNomics in Translational Medicine.

As a recent landmark discovery, his laboratory has shown that microRNAs originating from

injured brain can be detected in the peripheral blood samples and hence can be used as

36

diagnostic and prognostic biomarkers in stroke patients. Subsequently, he has

demonstrated that circulating blood microRNAs form ideal biomarkers in other related

diseases such as diabetes, hypertension and hyperlipidaemia. Thus far, Prof Jeyaseelan

has supervised 38 PhD graduates and has held several research, academic and

administrative positions in various universities including the University of Melbourne. At

present he also holds an Adjunct Professorship at the Monash University, Australia. Since

2011, his laboratory has been working closely with Prof Richards on microRNAs in heart

diseases. Under this TCR flagship program that is funded by NMRC, in collaboration with

several eminent clinical colleagues at NUHS and scientists in A*Star institutions, Prof

Jeyaseelan will be developing microRNAs as novel biomarkers for early diagnosis and

possibly as new therapeutic agents for cardiovascular diseases.

Colin Lawson Stewart

Senior Principle Investigator and Assistant Director

Institute of Medical Biology (IMB)

Prof Stewart graduated with a D Phil from the University of Oxford, UK, and has held

scientific posts in prestigious institutions in Germany and the US. He has pioneered many

techniques and made pivotal discoveries in stem cell and gene science. He developed the

technique of aggregating EC/ES cells with embryos to make chimeras and discovered that

EC/early embryos have a powerful de novo DNA methylation activity. He was instrumental

in discovering the role of the cytokine LIF in maintaining mouse embryonic stem (ES) cells.

Subsequently he demonstrated that, paradoxically, LIF was not essential for embryonic

development but was essential at regulating embryo implantation.

His long-standing interests include epigenetic regulation of gene expression, particularly

genomic imprinting. He developed the first androgenetic and parthenogenetic ES lines and

used these to identify novel imprinted genes and elucidate the role of imprinting in

regulating cell proliferation. He also determined the functions of three imprinted genes in the

Prader-Willi disease region. His current focus is the functional architecture of the cell’s

nucleus in stem cells, regeneration, aging and disease, particularly with regard to how the

nuclear functions integrate with cytoskeletal dynamics in development and disease.

Prof Stewart is a long-standing leader in the field of the laminopathies which underlie a

significant proportion of inherited heart disease.

37

Title of Programme

Non-Small Cell Lung Cancer: Targeting Cancer Stem Cell and Drug Resistance

Lead PI A/Prof TAN Eng Huat


Theme

PIs

A/Prof LIM Bing, Dr Axel HILLMER

Amount

Awarded

Tier 1- S$9M

Funding

Duration

Five Years

Objective of the Study

The study is targeted primarily at never-smokers with lung cancer. The objectives are four-

fold:

1) To conduct a comprehensive analysis of the cancer genome of never-smokers with lung

cancer in order to have a complete or near-complete view of the genomic mutations.

2) To look for novel genomic mutations other than those already known (refer above) that

can potentially be treated by new targeted agents. These new targeted agents can be

used in combination with standard treatment in order to enhance the efficacy of standard

therapies thereby prolonging quality survival.

3) To determine the spectrum of acquired genomic alterations that can contribute to the

onset of resistance to targeted agents and to design rational clinical studies combining

newer targeted agents with standard therapies to address these mechanisms of

resistance in patients.

4) To understand more deeply the behaviour of cancer stem cells that are believed to be

the source of cancer cell proliferations and to develop strategies to target this subset of

cancer cells that may lead to more durable remission of lung cancer and therefore

improve survival outcome.

To achieve these objectives, close collaboration amongst the researchers and with the

patients will be crucial. This is because patients need to understand the importance of

undergoing repeat biopsies, which can be invasive, in order to carry out the analysis of the

cancer genomes to aid the team in designing the clinical studies in a more rational manner.

Close collaboration has also been established with major pharmaceutical companies that

have a rich pipeline of new targeted compounds undergoing early phase clinical trials. As a

result, the team has put in placeseveral clinical trials that may potentially benefit patients in

terms of tumour control.

38


Lung cancer is a highly fatal disease and accounts for the highest cancer-related mortality in

Singapore and other developed nations. However, lung cancer is peculiar in Singapore and

other East Asian countries in that never-smokers comprise about a third of all lung cancer

diagnosed each year. The cause of lung cancer in never-smokers is still unknown. Most of

these patients are females and tend to be about a decade younger than the smokers.

Unfortunately, like smokers, less than 15% are diagnosed at an early stage. Therefore, the

majority of these patients would have an incurable disease when first diagnosed and the

treatment intent is palliative in nature.

Over the past decade, technological advances in analysing the genetic makeup of cancer

cells (or cancer genome) have led to the uncovering of alterations in genome that are largely

confined to never-smokers. These alterations have been shown to drive the growth of the

cancer cells. More importantly, we have drugs that target these alterations and block their

functions, thereby causing some of the cancer cells to die or stop growing temporarily. These

so-called targeted drugs are taken orally and tend to be associated with lower side-effects

than standard chemotherapy. Studies have also shown that these targeted agents are more

effective than chemotherapy in slowing down the growth pace of lung cancers that showed

the relevant genomic alterations.

However, physicians and patients continue to face significant challenges when confronting

the disease. Firstly, these targeted drugs are limited in efficacy. Not all patients with the

relevant genomic alterations respond equally well to these drugs. A minority do not respond

to these drugs at all. Moreover, the duration of the responses also varied greatly amongst

the responders with resistance setting in within one year of starting treatment for the majority

of responders resulting in regrowth of the cancer. Over the past five years, there has been

increasing understanding of the mechanisms of the acquired resistance to these targeted

agents. However, the understanding is still far from complete. More intensive research is

needed to address the shortcomings of the currently available therapies for lung cancer.

Another challenge is the lack of effective therapies for a significant proportion of never-

smokers who do not have the known cancer genomic alterations that can be treated with

targeted drugs. It is likely that these patients carry unknown genomic mutations in their

cancer cells that are yet to be discovered. Therefore detailed genomic studies of this group

of patients have to be urgently conducted in order to expand the treatment options for them.

39

There are currently two cancer genomic alterations found mainly in never-smokers with lung

cancer that can be treated with oral targeted drugs. The most common type is called the

epidermal growth factor receptor (EGFR) mutations which can be effectively treated by

targeted drugs known broadly as EGFR tyrosine kinase inhibitors or EGFR TKI for short.

Examples of EGFR TKI include gefitinib (IressaTM), and erlotinib (TarcevaTM).

The second type, which is found in about 5% of lung cancer in never smokers, is called

anaplastic lymphoma kinase (ALK) translocation, which predicts for good responses to a

targeted drug broadly known as ALK inhibitors. There is currently only one ALK inhibitor

approved for clinical use, which is crizotinib. These targeted agents have been shown to be

superior to standard chemotherapy in terms of proportion of good responders and duration of

responses. However as stated above, the majority of these patients will eventually develop

resistance to these agents within one year of treatment. Under such circumstances,

chemotherapy will be recommended as a second-line treatment option.

For patients that lacked EGFR mutations or the ALK translocations in their cancer genomes,

standard chemotherapy is generally recommended as the first-line therapy.

The key to understanding the behavior of cancer cells and the ways to counter them is

through a deeper understanding of the cancer genome. The next step would involve relating

the cancer genome information to the outcome of the therapies applied to the patients. By

doing so for a sufficient number of patients, we could derive information that can help to

predict which patients would respond to the particular treatment or not. These are deemed

the best steps to take, to make cancer treatment more personalised and optimised for

response and outcome.

To carry out this strategy, collaboration between scientists and clinicians is needed. More

importantly, the degree of collaboration between these researchers and patients is extremely

crucial to the success of this strategy. The patients need to be willing to contribute tumour

specimens and participate in clinical trials involving the newer targeted agents. The former

usually requires an invasive procedure to obtain fresh tumour specimens prior to

commencing on the new therapies. At times, a repeat biopsy may be needed to determine

changes in the cancer genome as a result of the therapies in order to better understand the

mechanisms of the drug action on the cancer cells.

40

Overall, this study brings together experienced scientists and clinicians who are experienced

researchers in lung cancer to look deeper into the above challenges facing never-smokers

with lung cancer.

TEAM’S PROFILE

TAN Eng Huat (LEAD PI)

Associate Professor Tan Eng Huat, Senior Consultant, Department of Medical Oncology,

and Head, Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre

Singapore

A/Prof Tan Eng Huat has been practicing medical oncology in Singapore since 1992 and

has been actively involved in lung cancer clinical trials since 1994. He has led several

international phase 2 and 3 clinical trials in lung cancer and is currently the head of the

Division of Clinical Trials and Epidemiological Sciences at the National Cancer Centre,

Singapore.

He is also one of the directors of a regional oncology research cooperative group called the

Cancer Therapeutics Research Group that comprises centres in Singapore, Hong Kong,

Taiwan, South Korea, and Australia. Dr Tan is also the principal investigator of Theme 3 of

this study, which is the conduct of translational clinical studies.

LIM Bing

Senior Group Leader, Stem Cell and Developmental Biology, Genome Institute of

Singapore (GIS)

Dr Lim Bing is Senior Group Leader for Stem Cell and Developmental Biology group at GIS.

Dr Lim’s research interest has centred around the biology of Stem Cells, beginning at the

University of Toronto studying blood stem cells followed by post doctoral work on gene

transfer into stem cells at Harvard Medical School where he is currently also Associate

Professor of Medicine. He took on a joint appointment at GIS in 2003 to develop a stem cell

program. Using a genomic approach in studying mouse and human embryonic stem cells,

he has sought to identify genetic factor controlling growth and transformation of stem cell.

More recently, significant parallel efforts have been made to study stem cells in diseases

such as cancer. As Director of Cancer Stem Cell Biology at GIS, and working with doctors

across Singapore, he seeks to accelerate the application of basic research discoveries in

clinical practices.

41

Dr Lim sits on several research, educational and ethics committee responsible for charting

research focus and efforts in Singapore. He also sits on review committees for research

grants in major international institutions and is on the editorial board of several research

journals.

Axel HILLMER

Senior Research Scientist, Genome Institute of Singapore (GIS)

Dr Axel Hillmer is a biologist with a human genetics background. He obtained his PhD at the

University of Bonn, Germany, in 2006 when he worked on the genetic causes of hair loss

disorders. Dr Hillmer joined GIS in 2008 and got a faculty position in 2011. His research

interest is in the genetic basis of cancer. His group uses modern next generation massive

parallel sequencing approaches to analyse patient tumor samples. He explores which

genes or chromosomal regions show mutations which in turn cause the disease and which

might be useful as drug targets. The identification of new drug targets is crucial for the

development of new therapeutic approaches against cancer. Dr Hillmer’s studies provide

insight into the processes which are involved the development of cancer.

Other participating clinicians and researchers

A/Prof GOH Boon Cher

Head, Dept. of Haematology- Oncology


A/Prof Goh has vast experience in early phase clinical trials and holds several research

grants including the coveted Clinician Scientist Award.

Dr Ross SOO & Dr CHIN Tan Min

Senior Medical Oncologists, Dept. of Haematology- Oncology


Dr Soo and Dr Chin have long established records in running clinical trials in lung cancer,

having published widely on this topic in top-tier international journals.

A/Prof Darren LIM & Dr Daniel TAN

Senior Staff Members, Dept. Medical Oncology

National Cancer Centre (NCC)

A/Prof Lim and Dr Tan are key clinician-researchers in upper aerodigestive tract cancers

including lung cancer. Both are experienced translational and clinical trial investigators

42

holding Individual Research Grant (IRG) grants in important translational research lung

cancer.

Dr Agasthian, A/Prof Koong Heng Nung, and Dr Su Jang Weng

Thoracic Surgeons at National University Heart Centre, Singapore (NUHCS), National

Cancer Centre (NCC) and National Heart Centre (NHC) respectively

They are crucial co-investigators for this study which is multidisciplinary in nature.

Dr Angela Takano

Senior Consultant Thoracic Pathologist, Department of Pathology

Singapore General Hospital

She will be handling the pathological aspect of this study and will work closely with the

scientists in optimising the tissues for sequencing and analysis.

43

Annex D

ACHIEVEMENTS OF THE BIOMEDICAL SCIENCES (BMS) INITIATIVE

How It Began

In 2000, the BMS Initiative was launched to establish BMS as the fourth key pillar of

Singapore’s economy, alongside Electronics, Engineering and Chemicals. This fourth pillar

encompassed the pharmaceutical, biotechnology, medical technology and healthcare

industries. Beyond BMS manufacturing, Singapore had to move up the value chain and build

a strong base in R&D.

Phase 1 (2000-2005): Building a Strong Foundation

Phase 1 of the BMS Initiative focused on building a strong foundation in basic biomedical

research for Singapore. We invested in infrastructure to create the Biopolis in One North,

raised the level of biomedical research institutes (RI) by establishing a strong foundation in

basic science capabilities, and attracted research talent that would form the heart of this

enterprise.

o Establishing a critical mass of excellent research talent

Internationally renowned scientists helped to jumpstart Singapore’s BMS efforts

by leading A*STAR BMS RIs and mentoring younger scientists. This group

includes top scientists such as Edward Holmes and Judith Swain from the

University of California, San Diego; Jackie Ying from the Massachusetts Institute

of Technology; and David Lane, the co-discoverer of the p53 tumour suppressor

gene.

To build a strong core of local talent for the long term, the A*STAR Graduate

Academy launched an ambitious scholarship drive to nurture a pipeline of

scientific talent for Singapore. Two years ago, we hit our target of awarding 1,000

scholarships to deserving and outstanding young people by 2010.

o Building a state-of-the-art research infrastructure

Biopolis Phase 1 was built and launched. This seven-building complex, which

housed five A*STAR RIs with capabilities in molecular and cell biology, genomics,

44

bioengineering, bioinformatics, and bioprocessing respectively, attracted an

accompanying base of private R&D laboratories and activities.

Phase 2 (2006-2010): Building up Singapore’s Translational and Clinical Research

Capabilities

Phase 2 of the BMS Initiative focused on building up Singapore’s translational and clinical

research (TCR) capabilities, while continuing to strengthen our foundation in basic research.

o Establishing key TCR infrastructure

During this period, A*STAR established five4 new BMS RIs/consortia with the aim

of accelerating the translation of basic research findings in the lab into clinical

applications to improve human healthcare. This was accompanied by the launch

of Biopolis phase 2, a two-building extension to house the new institutes as well

as other industry outfits.

o Deepening capabilities in TCR/ Developing Clinician Scientists

The National Research Foundation (NRF), through the Ministry of Health (MOH)

provided S$125m in block funding for five TCR Flagship Programmes from 2006

to 2010. Research areas were in neuroscience, gastric cancer, eye diseases,

infectious diseases and metabolic disorders. These were chosen taking into

consideration their relevance to Singapore’s healthcare challenges. The TCR

Flagships reflect a truly collaborative effort between clinicians and basic scientists

across various RIs and healthcare institutes in Singapore.

Some highlights include the Gastric Cancer programme which detected early

gastric cancer in 17 people, while also contributing new knowledge that

potentially impacts the detection and treatment for this type of cancer. Another

key success is the development of the world’s first robotic flexible endoscopy

system called Master and Slave Transluminal Endoscopic Robot (MASTER).

Patients benefit from less pain and a faster recovery from this no scar surgery.

4 BMRC's Singapore Institute for Clinical Sciences (SICS) and Institute of Medical Biology (IMB) conduct

translational and clinical research to bridge the gap between bench and bedside. BMRC has also launched consortia initiatives, which place significant emphasis on translational research in key areas, such as the Singapore Cancer Syndicate (SCS), Singapore Bioimaging Consortium (SBIC), Singapore Stem Cell Consortium (SSCC), Singapore Consortium of Cohort Studies (SCCS) and Singapore Immunology Network (SIgN).

45

The Eye programme has resulted in the development of a “made in Singapore”

product, the Tan EndoGlide, which is the first donor insertion device approved by

the Food and Drug Administration (FDA). It is a disposable device used in the

transplantation of the cornea. Another key outcome is the establishment of ReLEx

(Refractive Lenticule Extraction) SMILE (Small Incision Lenticule Extraction) as

an alternative surgical procedure to LASIK (Laser Assisted in Situ Keratomileusis).

Unlike LASIK, which uses two lasers and vaporises the corneal tissue to correct

vision, ReLEx SMILE uses only one laser for the entire procedure and removes

only an inner lens-shaped piece of cornea which corresponds to the patient's

myopia and/or astigmatism, through a keyhole incision in the cornea. Moving

ahead, the research team has patented a technology involving the

cryopreservation of the refractive lenticule, with focus on re-implanting into the

cornea. If successful, the surgical procedure can become “reversible”, hence

adding to patient safety and confidence. This technology (through A*STAR’s

Exploit Technologies) is currently licensed to a new spin-off company, Lenticor.

Other programmes have also made good progress. Although still early days, the

team working on the Metabolic programme, which was the latest programme to

be awarded in 2008, has managed to build up a birth cohort study named

GUSTO (Growing Up in Singapore Towards Healthy Outcomes). This is

Singapore’s largest and most comprehensive birth cohort studying the impact of

mothers' diet and lifestyle during pregnancy on their babies' growth after birth.

The cohort study has attracted interest from clinician experts and researchers

from around the world, as well as the nutrition industry.

In addition, to recognising the achievements of clinician scientists who had

devoted time and effort to TCR, MOH launched the Clinician Scientist Award

(CSA) and Singapore Translational Research (STaR) Investigator Award to

provide salary and research grant support to such individuals. As at June 2012, a

total of 12 awards have been given out under the STaR Award and 38 under the

CSA.

o Developing Medical Technology industry in Singapore

In 2009 at the International Advisory Council, Singapore announced that it would

be ramping up its BMS effort to develop the medtech industry in Singapore.

46

To that end, A*STAR established a collaboration with the Centre for Integration of

Medicine and Innovative Technology (CIMIT) in Boston, as well as the Singapore-

Stanford Biodesign Programme. These initiatives will see the collaboration of

Singapore BMS researchers and clinician scientists as well as their science and

engineering counterparts in the development of medtech technologies.

o Engaging industry

Creating economic value from R&D is an important outcome of the BMS initiative.

A*STAR, EDB and MOH have jointly set-up the Singapore Biomedical Sciences

Industry Partnership Office (BMS IPO). BMS IPO serves as the one-stop

coordinating office between the various research agencies and performers in

Singapore with industry players seeking to establish multi-party collaborations.

A*STAR also has a technology transfer arm called Exploit Technologies to

identify technologies with potential for commercialisation, and bring them to

market by licensing intellectual property and spinning off high potential companies.

It also has an Industry Development Group (IDG) under its Biomedical Research

Council (BMRC) which specialises in negotiating collaborations between pharma

and biotech players and the BMS RIs. These are powerful R&D collaborations

which involve the co-development of potential new products or new technology

platforms.

In addition, a new MOH initiative is being developed to harmonise the

commercialisation activities in the clinical community to foster closer

engagements with industry.

Phase 3 (2011-2015): Integrating for Greater Economic and Health Impact

Phase 3 of the BMS Initiative focuses on the integration of knowledge and capabilities across

disciplines and agencies to achieve even greater economic impact. Building on the success

in facilitating dialogue between biomedical scientists, clinicians and other professionals to

translate research findings into medically relevant applications will enhance our ability to

partner multi-disciplinary research collaborations with industry for greater impact.

The PM announced in 2010 that the Government has allocated $16.1 billion to R&D funding

over the next five years. This is based on a Whole-of-Government assessment of R&D

47

efforts across all agencies at a national level. For BMS R&D, the Government has committed

$3.7 billion over the next five years. This is a 12% increase over the $3.3 billion committed to

BMS R&D from 2006 to 2010. This is especially significant in the face of the shrinking R&D

budget in most countries.

This increase in funding to BMS will support three main areas to capture growing

opportunities arising from global trends in the BMS industry:-

o Enhanced Industry Engagements for Greater Economic Outcomes

BMRC will establish technology platforms that will bring together researchers

and groups from different disciplines in synergistic ways, so as to provide

multi-disciplinary solutions to problems of interest to industry. MOH and EDB

are supporting the National Cancer Centre Singapore and other healthcare

partners to establish the Roche Translational Medicine Hub, which will

facilitate the conduct of cutting edge research involving Singapore

investigators and Roche collaborators.

o Focusing on Mission-Oriented Programmes with high growth potential

A*STAR’s BMS R&D will focus on Mission-Oriented Programmes in the

Pharmbio, MedTech, Personal Care and Nutrition sectors, to draw on existing

strengths and capitalise on growing Asian markets to create better economic

value.

MOH’s research will focus on addressing key disease areas that are of

national and regional importance, and where Singapore has the potential and

capability to become a world leader.

o Seamless integration and translation as key competitive advantages

Biopolis, the integrated research campus for the Biomedical Sciences, clearly

demonstrates Singapore’s commitment and success in this sector. First

established in 2003, Biopolis has expanded through four phases, and houses

BMRC’s seven RIs, as well as research consortia, independent laboratories

and shared research facilities In addition, it houses R&D centres of more than

35 pharma, biotech and med tech companies such as Abbott, GSK, Merck,

Mesoblast, Novartis, Takeda and most recently, Chugai Pharmaceuticals and

Greatbatch.

48

This co-location in a single campus promotes opportunities for public-private

partnership, and A*STAR’s RIs have forged R&D collaborations with many of

these companies. In recent years, we have seen our research capabilities

attract interest from companies in the nutrition, skincare and consumer care

sectors; with companies such as Danone, Abbot Nutrition, and Procter &

Gamble also setting up R&D centres at Biopolis.

In the academic medical centres and healthcare institutions, MOH’s focus in

clinical research is evident through the establishment and continual funding of

the Singapore Clinical Research Institute as well as the two Investigational

Medicine Units at NUHS and SingHealth to support clinical trials and related

research. Clinicians now have access to key infrastructure and research

manpower support to bring key questions arising from their clinical

observations, to form properly designed and conducted research studies with

the eventual goal of improving clinical outcomes for patients.

embargoed till 6pm on fri, 9 nov 2012€¦ · 5. the programme can help to enhance singapore’s...

Documents