ACTRIS: A new national enabler for cell and gene therapies in Singapore

World Cancer Research Day is commemorated each year on 24 September and seeks to raise awareness of the importance of cancer research to increase survival, facilitate access to scientific advances worldwide and reduce the global burden of cancer.

Cancer is the second leading cause of death worldwide, and the global burden of cancer continues to grow. In Singapore, it is expected that 1 in 4 Singaporeans will be diagnosed with cancer by the age of 75. However, with many developing breakthroughs in early cancer detection and cancer treatment, a cancer diagnosis does not spell doom.

Advances in cancer research has opened up new ways to treat cancer with cutting-edge technology. Cellular therapeutics, commonly known as “living drugs” is one such example.

Singapore’s three-decade long history of performing hematopoietic stem cell transplants (HSCT) in both the public and private healthcare systems, and as a regional hub, is a key cornerstone clinical capability for the implementation of advanced cell and gene therapy (CGT) for the treatment of oncology and ageing associated diseases.

In this article, Dr Sudipto Bari, Head, Strategic Development and Communications at the Advanced Cell Therapy and Research Institute, Singapore (ACTRIS) ↗ (opens in new tab) introduces the evolution of CGT in Singapore, as well as the potential impact and benefits the continued development of cell therapy will bring to Singapore and beyond.

Cell and gene therapies offer hope for non-curable diseases

Cell and gene therapies (CGT) are the latest revolution in clinical care of non-curable diseases enabled through state-of-the-art manufacturing technologies. Given safety and efficacy data, in recent years, regulatory authorities across the globe have approved more than 60 CGT assets with an estimated 100 more products being considered for expedited approval. One such class of products are the chimeric antigen receptor (CAR) T cell that uses patients’ own immune cells, in particular T cells, to cure blood cancers.

In various landmark clinical trials, leading up to these CAR-T cell product approvals, patients with no other available standard of care underwent white blood cell collection processes in hospitals upon receiving appropriate chemo- and targeted-therapies. These live cells are then transported from the hospital to a current good manufacturing practice (cGMP) facility where it undergoes various stages of manufacturing including genetic manipulation that increases the specificity and potency of the patient’s T cells to fight cancers.

The highly skilled expertise required for CGT Manufacturing

CGT manufacturing requires clean rooms, specialised equipment and highly skilled manpower to achieve the therapeutic dosage of the potent cells to fight diseases inside the patient’s body.  The manufactured CAR-T cells undergo various testing and characterisations in clinical laboratories to ensure that they are safe and potent for patient’s administration in the hospital.

Despite its effective clinical efficacy, access to such life-saving therapies is limited by high cost, various manufacturing related complications, and the need to seek treatment at tertiary care hospitals with advanced clinical care infrastructure and capabilities.

Several of the challenges pertaining to manufacturing and cost of the therapies, could be overcome by performing manufacturing of the CGT assets at facilities near treatment centres or within a country’s own boundaries. In Singapore, the larger CGT processing facilities are located at the National University Hospital (NUH) and the Health Sciences Authority (HSA). These public sector manufacturing facilities support small-scale, investigator-driven clinical trials and clinical services of first-generation CGTs within our local hospitals.

In the ASEAN region, Singapore’s biomedical ecosystem, supported by the financial resources, is uniquely positioned to enable the innovation, adoption and commercialisation of CGT assets.

Tracing the development of CGT in Singapore

In the early days, the private sector contributed to the set-up of major CDMO facilities locally. This approach was taken to mitigate the high costs of CGT manufacturing and sophisticated infrastructure required at the time.

The foresight of the first generation of Singapore’s biomedical ecosystem architects established our existing cell therapy processing facilities within NUH and HSA by the late 2010s.

However, in the past five years since, there has been an exponential growth in the CGT ecosystem of Singapore fuelled by the developments mentioned above.

To meet the growing demands of CGT manufacturing, a centralised facility for manufacturing and process development of CGTs that will reduce the barrier to entry for new product developers was mooted.

A new national enabler for CGT manufacturing – the Advanced Cell Therapy and Research Institute, Singapore (ACTRIS) ↗ (opens in new tab) – was established to meet the increasing clinical demand of using CGTs. ACTRIS’s vision is to be the national and regional Centre of Excellence for facilitating discovery, process development and manufacturing of cellular-based therapeutics.

ACTRIS is a research programme of the Consortium for Clinical Research and Innovation, Singapore (CRIS), which brings together five key national-level R&D initiatives and clinical services. CRIS aims to make a positive difference to Singapore patients and researchers by ensuring that clinical research platforms and programmes such as ACTRIS, are at the cutting edge of capability development and innovation.

Promising developments for CGT to reach patients

Recently, HSA, implemented a comprehensive regulatory framework ↗ (opens in new tab) to govern the manufacturing, distribution and clinical usage of CGT assets. HSA’s regulatory guidelines for cell, tissue and gene therapy products (CTGTPs) have much convergence with similar guidance from countries/regions such as US, Europe, Japan and Australia, that have recently provided regulatory approval for the first commercial CGT product in Singapore.

As of September 2022, there are at least ten different clinical trials for CGTs in Singapore’s public healthcare system with at least another five to ten trials in the pipeline.

Furthermore, Singapore has set up donor registries and cell banks that are essential in the CGT industry, by leveraging its key value proposition to transport human cell products across its borders with all necessary safety measures and international compliance protocols in place.

In addition, the private healthcare insurance providers in Singapore have also started to reimburse approved treatments for CTGTPs while the government healthcare reimbursement plans continue to perform due diligence to review potential measures in the near future.

Singapore’s strategic geo-political positioning, established supply and logistics systems, supported by a strong transportation connectivity, has attracted contract development and manufacturing (CDMOs) companies to set up their regional sites within our borders.

In recent years, the start-up ecosystem of Singapore has enabled the formation of several ground-breaking local companies for CGT, while also attracting overseas start-ups, and a large number of multi-national pharmaceutical companies to land in Singapore for its expansion into the Asian markets and hospitals.

Moreover, biotechnology companies providing key raw / ancillary materials and equipment have also identified Singapore as a beachhead customer for many of its new technologies and assets that are enabling CGT manufacturing.

Leveraging the deep biomedical research and development capabilities, infrastructure and talent pool that have been fostered in Singapore over the past four decades, key public research funding agencies have recently awarded large collaborative grants in the space of CGTs.

These efforts by renowned research teams are enabling the targeted growth of both new CGTs and its manufacturing platform technologies to strengthen the innovative product pipeline in the clinical and economic systems of Singapore.

What’s next for CGT and manufacturing in Singapore?

Singapore is at the cusp to witness exponential growth within the CGT ecosystem, which will enable access to life-saving therapies for local and regional patients.

As such, amid the bustling developments highlighted above, ACTRIS’s vision remains well-placed to be the national and regional Centre of Excellence for discovery, process development and manufacturing of cellular-based therapeutics across the broad spectrum of immunotherapy and regenerative medicine, encompassing both investigational and approval products for the local market.

• Spearheading quality manufacturing of CGT - The ACTRIS manufacturing facility and full suite of cell therapy services are expected to be fully operationalised from the third-quarter of 2023. Once open, it will be accessible to the academic, public and private healthcare sectors.

• Support and foster collaboration within the cell therapy ecosystem - ACTRIS’s common goal is to promote and foster the entire value chain of the CGT ecosystem through enabling translational research and development, manufacturing, clinical service provision and commercialisation by serving the healthcare, academic and industrial sectors.

• Train and educate the next generation of scientists and clinicians in CGT - ACTRIS will also provide value-added services such as workforce training, regulatory facilitation and ancillary material standardisation pertaining to delivery of cellular therapy to patients.

In short, ACTRIS aims to capture healthcare and economic value through research translation into clinical applications and supporting public-private partnerships. In the years to come, with its sustained growth trajectory, Singapore is well poised to be the centre of excellence for clinical utility and manufacturing of CGTs for the region and beyond.