Investing in Innovation to Capture Next-Gen Therapy Potential
Advanced technologies, while important for the successful development and manufacture of next-gen therapies, are still a long way off being impactful, meaning more investment is needed to reap the rewards of these promising treatments.
Advanced and next-generation therapies, such as cell and gene therapies, are associated with numerous development and manufacturing challenges, such as the need for specialized ingredients, particular process requirements, and a high risk of contamination to name just a few. In this interview, The Pharma Navigator sat down with Erik Wiklund, CEO, Circio, and co-discoverer of circular RNA, to uncover more about the difficulties associated with the development and manufacture of next-gen therapies, the technological innovations that are providing help in overcoming these difficulties, and the need for investment from CDMOs to improve efficiencies.
Facing a Range of Challenges
TPN: Could you give an overview of the specific challenges pertaining to the development and manufacture of next-generation therapies?
Wiklund: The development and manufacture of next-generation therapies, including novel RNA formats, such as circRNA, viral and non-viral gene therapy, and other advanced biologics and cell therapies, face a range of challenges. These modalities often require novel raw materials, specialized delivery systems, and manufacturing processes that are not yet standardized across the industry. Therefore, manufacturing is often done at smaller scales with highly customized workflows, particularly for autologous cell therapies. The lack of established regulatory frameworks, limited availability of raw materials and skilled talent add further hurdles. In combination, these issues drive up cost, complexity, and development timelines.
Important Innovations
TPN: How can advanced technologies help to overcome these development and manufacturing challenges?
Wiklund: AI [artificial intelligence], automation, and closed-system production processes are all likely to be important to overcome the challenges associated with manufacturing of next-generation therapeutics. AI and machine learning can improve process optimization and real-time monitoring to enhance batch consistency. Automation helps reduce variability and contamination risk, which is particularly relevant for gene and cell therapies that currently require substantial manual handling. Closed-system platforms can support scalability and allow CDMOs to handle complex, small-batch production more efficiently. Innovations in these areas will be critical to ensure faster development timelines, reduce manufacturing cost and thereby ensure broader availability of next generation therapeutics for patients and healthcare providers.
A Long Time Off
TPN: Are there any potential areas where advanced technologies are not yet suitable for use or where further development is needed?
Wiklund: It will probably still take several years before these tools make a general impact on manufacturing. Advanced tools such as AI require large datasets to be effective, something that remains a challenge in early-stage development, especially for rare disease. The regulatory frameworks also need to catch up, and the ongoing restructuring and staffing reduction at the FDA does create a concern that this may be a bottleneck for wider adoption.
In addition, delivery technology for nucleic acid therapeutics and gene therapies is lagging as it remains a major challenge to effectively reach the right tissues and cell types to address many diseases. Current vectors and delivery systems, such as LNPs [lipid nanoparticles] and AAVs [adeno-associated viruses], work well for certain applications. However, delivery beyond liver and muscle is challenging with currently available technology. New delivery systems and novel RNA and synthetic DNA formats, such as circular RNA and nano-plasmid DNA (npDNA), are predicted to play an important role in solving these challenges and are areas we follow closely at Circio.
A Promising RNA Format
TPN: Can you provide some more details about circRNA?
cWiklund: Circular RNA (circRNA) is emerging as a promising RNA format with several advantages over traditional linear mRNA [messenger RNA]. circRNA forms a closed loop structure and is therefore resistant to the main RNA degradation pathway. This leads to increased and longer-lasting protein expression, which is a major therapeutic advantage, especially for gene and cell therapies and chronic disease.
In the context of gene and cell therapy, circRNA offers a flexible and durable platform for delivering genetic payloads, including gene-editing tools, antigens, or therapeutic proteins. Circio’s proprietary circVec system, a vector-based circRNA expression platform, enables in vivo production of circRNA directly from DNA templates, simplifying delivery and manufacturing. This approach combines the stability and expression advantages of circRNA with both established and novel viral or non-viral vector systems. In cell therapy, circVec can be used to safely engineer immune cells, such as CAR-Ts, without the need for genome integration, whilst achieving substantially longer durability than synthetic RNA transduction.
Overall, circRNA technologies like circVec open up new possibilities for next-gen therapeutics by bridging RNA stability, expression durability, and flexible delivery in a single platform. Access to advanced technologies supporting cost- and time-effective CMC development from CDMOs will be crucial to capture these opportunities in the coming years.
Supporting Faster Development
TPN: Why is flexibility particularly important for the increasingly complex development pipelines? How can advanced technologies help with this aspect?
Wiklund: Flexibility is crucial because biopharma companies are now managing an increasingly broad range of modalities and smaller patient populations, driven by the shift towards individualized treatment and rare disease indications. Advanced technologies such as modular, closed manufacturing systems, automation and AI will help enable switching between product types and scale. Such adaptability will support faster development by reducing risk and cost, which are important factors to incentivize development of complex therapeutics for small patient populations.
Investment Needed
TPN: How are CDMOs utilizing advanced technologies to drive forward innovation in next-gen therapies in your opinion?
Wiklund: CDMOs should invest in novel technologies such as single-use and automated platforms to reduce development cost and timelines of novel RNA and DNA formats and gene and cell therapies. This seems to be happening to some degree, however, from the perspective of a small biotech with a limited budget, more and faster progress is needed, or many therapeutic opportunities will remain out of reach at a time when capital is severely constrained. Hopefully, the increasing competition between CDMOs and accelerating switch to novel therapeutic formats, will incentivize more and faster innovation to capture these new market opportunities.
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