From small molecules wedged in cryptic pockets to gene modification and mRNA therapy, drug discovery is an all-encompassing search for new ways to target and change biology. With old disorders still at large and new diseases entering the scene, that search has never been more relevant for our health and quality of life.
Drug discovery and development (DDD) begins with identifying a candidate target. Many types of biological molecules, such as genes and proteins, can serve as drug targets. These typically emerge from decades of basic biomedical research into a particular molecule, exploring its cellular function and relevance to human disease.
From this starting point to commercial approval, the DDD process may take 10 to 15 years. Notably, few drugs that begin this journey make it all the way through; the overall likelihood of approval for a drug entering Phase 1 development is typically under 10 percent. As a result, many promising drug candidates might not reach the patients who stand to benefit from them.
Over the past decade, Singapore’s investments in biomedical research have helped to establish a strong foundation for scientific talent to thrive and new capabilities to emerge. DDD efforts built on this foundation have generated valuable returns for the nation economically and societally, creating valuable solutions for unmet patient needs at home and abroad. As a strategic innovation engine for Singapore, A*STAR’s various platforms and initiatives have helped translate cutting-edge discoveries into real-world treatments.
Support from lab to clinic
Many A*STAR research institutes have deep expertise in uncovering new targets and drugs. These include the Bioinformatics Institute (BII), the Singapore Immunology Network (SIgN), the Institute of Molecular and Cell Biology (IMCB), the Genome Institute of Singapore (GIS), A*STAR Skin Research Labs (A*SRL) and A*STAR Infectious Diseases Labs (ID Labs).
One national platform that harnesses these diverse capabilities from A*STAR and its partners toward effective DDD is the Experimental Drug Development Centre (EDDC). Formed in 2019 and hosted by A*STAR, EDDC merged three then-existing government-funded units: the Experimental Therapeutics Centre (ETC), Drug Discovery and Development (D3), and the Experimental Biologics Centre (EBC).
“Our vision was to create synergies by combining extensive capabilities in small and large molecule discovery, as well as preclinical and clinical development, to more effectively translate innovative biomedical discoveries in Singapore into new and impactful treatments,” explained EDDC Chief Executive Officer Damian O’Connell.
COMMITMENT TO SCIENCE
As a national DDD platform, EDDC aims to bridge gaps in the field and catalyse the growth of Singapore’s biopharmaceutical ecosystem through its activities and partnerships. Working actively with other academic, research and medical institutions, EDDC’s efforts focus on:
1. Identifying and nurturing promising drug discovery projects from their earliest stages.
2. Providing expert guidance to investigators.
3. Applying its technical capabilities and expertise to discover and develop therapeutic drug candidates which address unmet medical needs and can bring commercial value to Singapore.
Other EDDC capabilities include Chemistry Manufacturing and Control (CMC), in vivo pharmacology (including in vivo efficacy, pharmacokinetics as well as toxicology and safety evaluations) and regulatory affairs.
The platform’s value in Singapore’s DDD efforts was exemplified in its COVID-19 response. As the pandemic emerged, EDDC and BII co-developed one of the world’s first COVID-19 detection kits—the Fortitude Kit—in collaboration with Tan Tock Seng Hospital and the Diagnostics Development Hub (DxD Hub).
EDDC’s development team also collaborated with DSO National Laboratories (DSO), the National Centre for Infectious Diseases, the National University of Singapore and local biotech Hummingbird Biosciences to drive the preclinical and clinical development of DSO’s COVID-19 neutralising antibodies.
“EDDC’s role is to translate Singapore’s great science into great medicines,” said O’Connell, adding that going forward, he hopes to see more drug discovery ideas and projects arising from the local community.
Apart from the EDDC, another key line of support for DDD projects is the Singapore Therapeutics Development Review (STDR), which merges grant schemes for early-stage therapeutics projects from A*STAR, the Singapore-MIT Alliance for Research and Technology (SMART) and the National Health Innovation Centre Singapore (NHIC).
“STDR has journeyed from its origins as a small A*STAR initiative for systematic reviews and targeted support of the agency’s therapeutics projects to what it is today: a national funding scheme to boost Singapore’s DDD pipeline and to groom its scientists as biotech entrepreneurs,” said Sze Wee Tan, Assistant Chief Executive (ACE) of A*STAR’s Innovation and Enterprise (I&E) Division, in a speech at the 2022 STDR Symposium.
From 2019 to 2022, STDR supported 20 projects over six cycles, which led to four additions to EDDC’s portfolio, three spinoff biotech companies and two codeveloped assets with pharmaceutical companies. “We’re proud to say STDR has been effective in supporting early-stage therapeutics projects for translational and commercialisation outcomes,” said Tan.
A multifaceted team effort
Regardless of access to expertise or resources, DDD remains an arduous and long journey with no promise of success. “It is said that it takes 10,000 ideas to get one drug,” commented O’Connell, implying that most projects fail along the way.
Huck Hui Ng, ACE of A*STAR’s Biomedical Research Council (BMRC), agrees. “Drug discovery is a complex and lengthy endeavour, accompanied by a high level of uncertainty,” said Ng, also the Senior Group Leader of Precision Disease Therapeutics at GIS. “Therefore, a multitude of approaches is necessary for us to rigorously investigate and uncover new targets and drugs.”
That multitude calls for a team effort to improve the odds. To this end, A*STAR has developed diverse capabilities across research institutes which encompass fields such as computational biology, delivery, omics, immunology, bioprocessing, and molecular and cell biology.
Given the breadth and scope involved, and the need to integrate interdisciplinary approaches, A*STAR is also simultaneously adopting artificial intelligence (AI) and advancing its computational capabilities in diverse ways to accelerate drug discovery efforts across the entire value chain.
“We’re developing novel AI tools that can be used in a variety of ways, such as to predict the structure and properties of RNA,” said Yew Soon Ong, A*STAR’s Chief AI Scientist, adding that AI opens a door to novel therapeutics and target identification.
AI tools can also analyse large volumes of biological and chemical data to identify new drug candidates. “For example, researchers at A*STAR’s Institute of High-Performance Computing (IHPC) have designed advanced deep learning-based algorithms that can accurately predict the binding affinity of small molecules to target proteins,” said Ong.
By working together, researchers from different institutes can pool domain expertise and resources to tackle DDD from a range of perspectives. “For instance, EDDC is working with GIS to accelerate the development of new RNA-targeting therapeutics. The platform is also supporting BII and IHPC in designing drug candidates to target newly discovered allosteric or cryptic binding sites on proteins, which could lead to better treatments with minimal side effects,” added Ong.
AVENUES OF DISCOVERY
To A*STAR, cross-disciplinary research is key to addressing complex biological problems in DDD. Among such efforts supported by the agency are antibody development platforms (ADP) under development by A*STAR’s Bioprocessing Technology Institute (BTI) Deputy Executive Director Andre Choo and colleagues. Their ADP has helped spearhead the discovery, development and in vitro/in vivo characterisation of novel monoclonal antibodies for therapeutic applications.
In January 2023, EBC-129, an antibody-drug conjugate, was approved for first-in-human clinical trials by the US Food and Drug Administration and Singapore’s Health Sciences Authority (HSA). EBC-129 emerged from an initial collaboration between Choo and Daniel Tan from the National Cancer Centre Singapore, which uncovered the parent antibody preceding EBC-129 and characterised its unique target epitope.
Subsequently, the antibody was further characterised and co-developed with the EDDC into an antibody-drug conjugate for entry into clinical trials. “EBC-129’s approval is a testimony of our platform and reflects the maturity of Singapore’s DDD ecosystem to collaborate and deliver end-to-end outcomes,” said Choo, who is also Executive Director at BMRC.
Another promising avenue in DDD, particularly for cancers, is immunotherapy; drugs that modify the immune system to fight disease. At IMCB, Research Director Qi Zeng is studying potential immunotherapies targeting pro-cancerous proteins known as oncoproteins, with a focus on Phosphatase of Regenerating Liver 3 (PRL3), an intracellular protein overexpressed in many tumours.
Her research and extensive expertise led to her co-founding Intra-ImmuSG (IISG), an A*STAR spinoff Phase 2 clinical-stage biotechnology company. Since its inception, IISG has generated PRL3-zumab, a humanised antibody that moved into first-in-man Phase 1 trials in 2017.
“PRL3-zumab is an innovative antibody drug that provides a new opportunity for hard-to-treat cancer patients, has an excellent drug safety profile and demonstrates early efficacy in some patients,” said Zeng.
On a broader scale, SIgN Principal Investigator and head of the Human Innate Immunity Lab, Subhra K. Biswas, takes a systems immunology approach to discover novel immune targets and biomarkers for various diseases. Rather than studying molecules and cells in isolation, this approach analyses the interactions between them and their global impact in driving disease.
Using deep immunoprofiling, Biswas and colleagues analyse blood or tissue biopsies from patients to identify targets for mechanistic studies with in vitro models. Potential new compounds are then tested in humanised mice to provide a pre-clinical basis for their therapeutic use.
“We are applying such an approach in the IAF-PPfunded Singapore Immunogram for Immuno-oncology (SIGNAL) programme to decipher and predict the response of cancer patients to immunotherapy, which has attracted several clinical and industry partners to work with us,” said Biswas.
Beyond small molecules and protein targets, A*STAR also employs advances in genome editing in DDD. By changing specific sequences in the human genome using safe and effective therapeutics, diseases with underlying genetic origins could potentially be cured.
This is the hope of GIS researcher Wei Leong Chew and the Synthetic Biology and Genome Editing Therapeutics group, who engineer DNA and RNA using technologies such as CRISPR-Cas9 and adeno-associated viruses (AAVs) as delivery vehicles to correct genetic aberrations and ultimately treat disease.
“From a novel base editor system to an antiviral CRISPR therapeutics modality, our research seeks to develop innovative gene editing technology with significant intellectual property value and clinical potential,” said Chew.
Leaning on industry partnerships
A*STAR’s industry partners are key components of the DDD pipeline, especially when drug candidates reach advanced stages (Phase 2 clinical trials and beyond).
“Biotech or pharma companies have the specialised infrastructure, capabilities, expertise and experience to support a drug candidate’s advancement through clinical trials and beyond,” said O’Connell. He added that their financial muscle drives the clinical development and manufacturing of drug candidates which comprise complex, expensive and highly regulated processes.
One dedicated A*STAR platform that unites public research expertise with industry capabilities is the Pharma Innovation Programme Singapore (PIPS). Employing novel manufacturing technologies and data analytics, PIPS enhances productivity and operational efficiency within Singapore’s pharmaceutical sector through the synergy created with its partners.
Under RIE2025, PIPS was expanded into BioPIPS, an initiative that included biologics and vaccine manufacturers in efforts to enable more companies to work on pre-competitive co-innovation. “BioPIPS aims to strengthen and transform Singapore’s local biomanufacturing capabilities and facilities into agile factories of the future,” said Keng Hui Lim, Assistant Chief Executive of A*STAR’s Science and Engineering Research Council (SERC).
With capabilities in areas like advanced sensing, robotics, modelling and sustainable materials, BioPIPS aims to enhance manufacturing productivity using sustainable processes. “This initiative is also in line with Singapore’s Manufacturing 2030 vision of increasing manufacturing value by 50 percent from 2020,” added Lim.
Through BioPIPS, A*STAR has formalised partnerships with global pharma giants GSK, Sanofi and Takeda to boost innovation in biologics and vaccine manufacturing in Singapore.
“When a pharmaceutical company partners with an academic institution, the former gains access to cutting-edge research and technology, while the latter may benefit from the former’s expertise in downstream drug development and regulatory approval,” said Sze Wee Tan.
Beyond large industry players, A*STAR also supports many local biotech startups in advancing therapeutic assets through the agency’s initiatives, technology licenses and joint laboratories (see diagram).
Eyes on the goal
DDD is a long and complex multi-stage process which calls for collaboration at every step; between public and private sectors, academia and industry, local and international players, and small and large companies. “[These] partnerships bring together the complementary expertise, resources and technologies necessary to develop new treatments and drugs,” said Tan.
Through a multidisciplinary approach and its collaborative network, A*STAR sets the stage to successfully bring novel medicines into clinical trials. The agency provides a strategic engine to strengthen the R&D pipeline from basic research to commercialisation, bringing strong investments and grooming new talent. “We hope to drive impactful research that can advance human health and create economic value for Singapore and Singaporeans,” said Ng.
“Like every drug developer, we’re motivated by a wish to see our products reach the patients who need them,” concluded O’Connell. “We keep this end goal in mind to remind ourselves why we do what we do, and of the potential impact we can create.”