The Singapore Biotech Insights series is a new initiative jointly organized by the Singapore Economic Development Board (EDB) and Biotech Connection Singapore (BCS). This series of events aims to foster stronger connections within the local biotech community in Singapore through featuring several current and exciting topics in biotech. Thereby bringing together various stakeholders in healthcare, tech and other sectors to participate in rich, interactive and enlightening discussions with experts in the field, and providing a networking platform to catalyze the formation of valuable new partnerships.
The first event of this series- “The Cell Therapy Revolution” was held on the 21st October 2019 and jointly organized by BCS, EDB and SGInnovate and partnered with A*STAR A*ccelerate and Enterprise Singapore. The event aimed to discuss the latest progress and challenges in the burgeoning field of cell therapy by bringing together various stakeholders including pharma, biotech, academia, investors and regulators. Held in the EDB office in Raffles City Tower, the event received an overwhelming attendance of over 200 participants eager to learn and discuss the dawn of this new therapy.
The event was kicked off by a keynote address by Dr. Didier Dargent (DD), Head of International Markets for Cell and Gene Therapy at Novartis Oncology. Didier introduced the concept of cell therapy, explaining that this form of therapy was vastly different from the traditional pharmaceutical drugs as it involved engineering the patient’s own immune cells to fight their cancer. The first cell therapy product from Novartis- Kymriah, involves a Chimeric Antigen Receptor (CAR) protein modality which recognizes the target CD19 on leukemic cells. During CAR-T development, the patient’s own immune T cells are engineered to express the CAR which enables them to recognize and kill the cancer cells with great efficacy. Most strikingly CAR-T cells were efficient in clearing cancer in “patients who had few weeks of life expectancy and whose cancer was resistant to all lines of existing treatment”. Thus CAR-T therapy is revolutionizing oncology treatment by “bringing innovation to the patients without hope”.
Despite the overwhelming promise and growing clinical trials in this field, there are currently only two CAR-T products approved for commercialization including Kymriah from Novartis and Yescarta from Gilead. Didier outlined several challenges that pharma companies face when commercializing this group of therapeutic products. The unique nature of CAR-T manufacturing and delivery has posed a disruption to the traditional model of drug manufacturing and supply chain logistics. Majority of existing biopharmaceutical products are produced at a manufacturing plant in millions of drug units and sold to pharmacies around the world via distributors. CAR-T therapy, on the other hand, requires the patient cells as one of the raw materials in the manufacturing process- this first step limited by diagnosis and cell collection in hospitals. Furthermore, the shipment logistics for CAR-T from patient to manufacturing plants and back into the patients, demands the highest level of “IT systems, full chain of patient identification, transparency and follow up to ensure patients receive the right treatment”.
Dr. Didier Dargent presenting Novartis’ oncology pipeline which includes cell and gene therapy
The panel for the event consisted of a diverse set of expertise discussing various elements involved in bringing successful cell therapy products to the patients. The discussion was moderated by Chris Hardesty (CH), Director of Life Sciences Practice at KPMG. Along with vast expertise across the healthcare sector, Chris has been involved with supporting CAR-T launches in Asia. He first asked the panelists to share their views of the cell therapy field from their different expert perspectives.
Antonio Bertoletti (AB), Professor at Duke-NUS Medical School and Scientific Founder at biotech company Lion TCR, elaborated on the scientific principles underlying these therapies. Antonio outlined how identifying important tumor specific antigens remained a key challenge in expanding these therapies to other cancers and hence remained an area of active research. He introduced a different type of cell therapy where T cells were redirected against their targets by a different protein structure called T Cell Receptor (TCR). TCR-redirected T cells are able to “recognize pieces of antigen targets produced inside of cancer cells and presented on the cells’ HLA molecule”. He had developed a library of TCRs targeting the Hepatitis B Virus proteins in liver cancer through his academic research and these were now being harnessed by the biotech company Lion TCR for their therapeutic TCR-T cell therapy products.
Chris Hardesty introducing the panel (seated from left to right; Prof. Antonio Bertoletti, Dr. Khoo Shih, Dr. Srinivasan Kellathur)
Dr. Khoo Shih (KS), Managing Director of Life Sciences Investments at Temasek, agreed that “the cell and gene therapy space will be a really transformative and important modality along with existing treatment modalities for many diseases including cancer”. Hence, investment in this area was promising with these therapies potentially extending to other cell types for treatment of multiple diseases. She elaborated that the cell therapy space had grown over the last decade, with over 500 companies, 1000 global clinical trials and more than 6B USD financing raised by this sector at start of 2019. She believed that “while the space has grown, this therapy is still in its early innings of showing potential” and further advances in technology and know-how were necessary to overcome current limitations. To target solid tumors, better ways to engineer cells to resist the suppressive tumor environment are needed. Advancing from autologous (patient’s own cells) to allogenic therapy (healthy donor derived cells and renewal cell source such as iPSC based) would be important to reduce cost and delivery complexity. In addition, new healthcare payment models would be needed to enable patient access to these potentially curative therapies.
Dr. Srinivasan Kellathur (SK), Director of Advanced Therapy Products Branch at the Health Sciences Authority (HSA), shared the efforts of the Singapore regulatory authority at charting new regulatory framework for cell, tissue and gene therapy products (CTGTP) since the current biopharma framework was not suited for this group of products. As part of the new framework, HSA was also planning to release specific guidance documents that are relevant for CTGTP product development and manufacturing. He further elaborated how Singapore had taken a front foot on the regulatory aspect of advanced therapies, being nominated by the Asia Pacific Economic Cooperation (APEC) as the lead economy to “chart out a roadmap for these therapies by aligning scientific principles, regulatory frameworks and best practices” in the APEC region. Given the new and evolving nature of these products, a real effort at regulatory harmonization and convergence was being undertaken by the economies around the world to avoid regulatory divergence. A key aspect of this harmonization process included providing training to regulators, healthcare practitioners and biotech companies and this training process was being carried out at the Duke-NUS Centre for Regulatory Excellence (CORE) in Singapore and Biopharmaceutical Analysis Training Laboratory, Northeastern University, Boston in the USA.
After sharing their in-depth perspectives, the panel continued to discuss the challenges and advances to come in the cell therapy field. Some of the key discussions are outlined below:
Addressing manufacturing bottlenecks in cell therapy
CH: As these products become available in growing number of countries, where do you see the main bottlenecks in the development of these therapies?
DD: The main challenge has been to scale up which requires specialized human resources and efficient manufacturing processes. If any component of the process is varied, including temperature, then another approval is required. Hence the challenge is how to increase the quantity of products while maintaining the quality and efficiency of manufacturing since a lot of parameters will impact the process.
SK: Manufacturing of cell therapy is challenging in general for cell therapies and specifically for autologous products. Depending on the product, regulators look at the entire supply chain from apheresis to final product, although this may be more straightforward for allogeneic products.
The potential of allogeneic therapy
CH: What are allogeneic cells and where are they now? What is the difference between autologous and allogeneic and where are we in this journey?
KS: Autologous therapy involves engineering patient cells and infusing them into the same patient. This process requires complex logistics and the quality of cells varies from patient to patient. Allogeneic therapy on the other hand uses different sources of cells including:
- Healthy cell donor bank, whereby the donor cells are engineered to mask them from rejection by the patient’s immune system. Several companies are currently developing this type of allogeneic therapy and these are a few years away from approval.
- Renewable cell source such as induced Pluripotent Stem Cells (iPSCs) which provides a consistent master cell bank for manufacturing. iPSC-derived allogeneic therapy is closer to the traditional biopharmaceutical products and hence has more potential for overcoming manufacturing, supply chain logistics but poses different biological challenges.
SK: From a regulatory perspective, quality, safety and efficacy will be the main parameters assessed for allogeneic products along with additional donor screening to ensure eligibility and safety tests such as tumorigenicity tests for iPSC-based allogeneic therapies.
Prof. Antonio Bertoletti explaining the outstanding research questions in cell therapy
The Singapore ecosystem in the cell therapy space
CH: How does the Singapore R&D and biotech ecosystem compare with other countries? How do we make sure Singapore stays a vibrant ecosystem?
AB: The cell and gene therapy field is technologically intense and difficult. The ecosystem in Singapore is equipped with both excellent basic research and clinicians that can apply this complicated therapy into clinics.
KS: Singapore is well positioned to capture the cell and gene therapy innovation space given the availability of talent in the manufacturing, automation and analytics and the regulatory leadership in this region.
SK: There are a lot of local biotech startups currently doing cell therapy trials in Phase III and also in early Phase settings. Seeing how locally developed products can enter the market and benefit patients will be an exciting space to watch.
The event concluded with networking of the participants with the panelists and speakers over refreshments. The organizers would like to thank all the panel members, speaker and moderator for contributing their expertise on the topic of cell therapy and to all the participants for their engaging interest!
By Mayura Wagle on behalf of BCS