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FEATURE
Strengthening Singapore’s Drug Discovery Capabilities through Public Private Partnerships
Dr. Alex Matter
CEO, Experimental Therapeutics Centre (ETC)

Introduction

Public private partnerships (PPPs) between public organizations and pharmaceutical companies have contributed to the development of the biomedical sciences industry in Singapore. Efforts to build up the industry started with the launch of the Biomedical Sciences Initiative in 2000. Singapore’s long term goal is to create a sustainable and vibrant biomedical sciences sector, which encompasses a pharmaceutical industry that has strong capabilities across the entire pharmaceutical value chain from R&D to commercialization to manufacturing. Even in the early days, PPPs were critical in helping the local sector attract pharmaceutical investments and develop key capabilities in R&D.

Contributions of PPPs

The Novartis Institute for Tropical Diseases (NITD) is one of the earliest PPPs in Singapore dedicated to the development of new drugs against neglected diseases. NITD was established with the combined financial, manpower and IP resources of Novartis and public organizations in Singapore, including the Economic Development Board (EDB) and the Agency for Science, Technology and Research (A*STAR). NITD’s drug discovery efforts have certainly achieved some success. For example, working together with research partners such as the Genome Institute of the Novartis Research Foundation, the Swiss Tropical and Public Health Institute and The Scripps Research Institute, NITD has discovered two new classes of anti-malaria compounds. Two drug candidates (KAE609 and KAF156)1 are currently in clinical trials and may potentially provide completely new treatment options for the disease. More recently, in late 2013, research efforts have yielded another novel malaria drug target — phosphatidylinositol-4 kinase (PfPI4K)2.

Just like NITD, Singapore’s biomedical sciences industry has grown over the years in terms of R&D capabilities and capacity. Currently in the third phase of its Biomedical Sciences Initiative, Singapore is strengthening engagements between the public research sector and the industry as well as fostering integration of various research groups to facilitate translational research within the industry, in order to generate greater healthcare and economic impact. Effective PPPs that bring public research organizations and private companies together will contribute significantly to the achievement of these goals. Such PPPs can also facilitate greater collaboration among Singapore research institutes. In the area of pharmaceutical drug discovery and development, the Experimental Therapeutic Centre (ETC) and its sister organization, D3, are front runners that are actively engaging the pharmaceutical industry to develop innovative drugs targeting diseases that represent huge healthcare burdens. They were set up with private-public partnerships in mind, specifically to fill the innovation gap that straddles academia research and late stage research in pharmaceutical companies (see Figure 1).

Experimental Therapeutics Centre (ETC)

ETC takes a unique partner-oriented approach when collaborating with industry players, to meet their needs and to support their efforts in translating early stage drug discoveries into drug candidates. It has a full suite of integrated drug discovery capabilities to identify drug hits and leads, and develop them into preclinical development candidates (PDC). These capabilities include:

  • Biochemistry/Assay development/Analytics
  • High throughput screening (with a library of 500,000 compounds)
  • Structural biology
  • Mass spectrometry (including Rapid Fire technology)
  • High-end Nuclear Magnetic Resonance (NMR)
  • Medicinal chemistry (with access to 40 highly skilled chemists)
  • Pharmacology/Metabolism/Preliminary toxicology

In addition, ETC is embedded into the local R&D network, allowing it access to common or shared resources and a variety of technology platforms. Since its establishment, ETC has successfully worked with a number of private companies on joint research projects that benefited from ETC’s proven early stage drug discovery expertise and its strong commercial focus. Two of these are described below:

Oncology Drug Development with Debiopharm

In early October 2013, Debiopharm, a Swiss biopharmaceutical company, entered an R&D partnership with ETC to develop oral small molecule drugs to fight cancers with epigenetic lesions. Such lesions are understood to be heritable changes of gene activity that are not caused by changes in the genetic code itself. Epigenetics represents a rapidly growing and promising field in cancer medicine. Research efforts will focus more broadly on the exploration of epigenetic targets — an approach that is emerging as an effective personalized medicine strategy for cancer treatment. ETC is driving the project, which is currently ongoing and has seen some early results.

Antimicrobial Agent Development with AstraZeneca

Gram-negative bacterial infections are responsible for two thirds of deaths in all hospital-acquired infections. Gram-negative bacteria are resistant to multiple drugs and are becoming resistant to most available antibiotics. AstraZeneca and ETC formed a collaboration in May 2013 to develop new antimicrobial drugs targeting Gram-negative bacteria. This ongoing effort, led by ETC, allows both parties to combine their efforts, expertise and experience to address an urgent global healthcare threat.

D3 – Drug Discovery & Development

A*STAR’s D3 was established in 2012 as a platform to take projects through early stages of the development process from preclinical development candidates to ‘proof-of-concept’ (PoC)* studies in humans. D3’s range of activities covers preclinical development, biomarker development and the conduct of early clinical trials, with specific activities that include:

  • Good Manufacturing Practices (GMP) manufacturing
  • Formulation
  • Good Laboratory Practices (GLP) ADME
  • GLP Toxicology
  • Tolerability
  • Pharmacokinetics
  • Biomarkers
  • Good Clinical Practices (GCP) Clinical Trials

D3’s overall mission is to perform translational R&D on biomedical discoveries made in Singapore and elsewhere, to develop new medicines that will have a significant healthcare impact in improving patients’ lives. With strong support from the Singapore government, it has the talent, resources, and expertise to take on new chemical entities (NCEs) and biologics that have reached the preclinical-development candidate stage through early development and early clinical trials in humans. Once compounds have successfully achieved PoC status, D3, together with Exploit Technologies Pte. Ltd. (ETPL), the commercialization arm of A*STAR, will focus on licensing the compounds to pharmaceutical or biotechnology companies for further global development and launch. One example is described below:

D3’s Industry Collaboration Efforts – Singapore’s First Influenza Vaccine

The H1N1 influenza pandemic emerged in Singapore in 2009, infecting a large segment of the country’s population and resulting in 30 deaths. Today, H1N1 is established as a new endemic flu strain, although luckily without being a major global healthcare threat. Cytos Biotechnology in Switzerland collaborated with A*STAR to develop a virus-like particles (VLP) vaccine against the deadly disease using the company’s unique technology platform. The project was first led by ETC, and then by D3. It also involved multiple research groups and stakeholders in Singapore including other A*STAR institutes (Singapore Immunology Network (SIgN)6, Genome Institute of Singapore (GIS)7), Duke-NUS Graduate Medical School Singapore8, Singapore’s healthcare network (Singapore Clinical Research Institute(SCRI)9, National University Health System (NUHS) Investigational Medicine Unit (IMU)10, Singhealth IMU11) and the Defence Science Organisation (DSO) National Laboratories12. The project has achieved its planned goal of immunogenicity in healthy volunteers based on a completed Phase 1 clinical trial. Equally important, it showcases how PPP can lead to greater collaboration among research institutes in Singapore.

Sustaining Partnerships with the Pharmaceutical Industry

In recent years, large pharmaceutical companies and venture capital investors within the drug discovery sector have become more cautious. They are typically less willing to invest in early-stage projects or prefer to engage in projects where major or risk hurdles have already been overcome. It is within such a context that organizations like ETC and D3 have been created — to become cost-effective and professional development partners that are able to advance and add value to early-stage projects on a ‘shared risk, shared reward’ basis.

Public research organizations such as ETC and D3, as well as their peers in Singapore’s close-knit biomedical R&D community, host many critical drug discovery and development capabilities and resources. Through PPPs, these capabilities are constantly being sharpened and their associated resources are put into effective use, resulting in benefits for the industry, for the nation’s healthcare, and ultimately for the patient.

About the Authors

Professor Alex Matter, M.D., is CEO of the Experimental Therapeutics Centre, A*STAR, Singapore. He spent five and a half years as Director of the Novartis Institute for Tropical Diseases (NITD), from October 2003 to February 2009. Prior to this role, Dr. Matter was Global Head of Oncology Research for Novartis Pharmaceuticals Corporation, Head of Novartis Institutes for BioMedical Research in Basel and Global Head of Translational Research.

Dr. Matter played an important role in the success of several anticancer drugs, including Gleevec/Glivec®and more recently, Tasigna®, building and leading the teams that discovered these and several other anticancer drugs as well as one HIV protease inhibitor (Reyataz®) that is marketed by another company.

Dr. Matter received his medical degree from the University of Basel. He also had fellowships at the Swiss National Science Foundation and the Swiss Academy for Medical Sciences. He has published more than 100 scientific articles and several book chapters in the area of oncology and hematology. He is emeritus Professor of the Medical Faculty of the University Basel and an Honorary Adjunct Professor of the Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore.

He is a member of the American Association for Cancer Research, the National Medical Research Council in Singapore, and the Board of Curiox, a Singapore-based start up company. He is also an elected member of the Swiss Academy of Medical Sciences. Dr. Matter is the recipient of the 13th Warren-Alpert prize and the AACR-Bruce F. Cain Memorial Award.

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