Investment and market

Economic pressures
One of the biggest challenges for CGT developers heading into 2025 is the continued strain of the capital markets, which has slowed progress and shifted focus toward advancing their most promising drug candidates. This has often come at the expense of investing in new manufacturing technologies essential for bringing these therapies to market. However, it remains critical to design cost-efficient processes that minimize both investment and operational costs, paving the way for successful market entry.

One avenue is to turn to decision-support tools to help make better-informed choices early in discovery and development. Cost modeling tools are supporting developers to make data-driven decisions such as selecting the appropriate technology platform, defining scale-up or scale-down strategies, and making make-or-buy decisions. These tools can help maximize the chances of success for therapies when reaching commercial scale, even under constrained resources. Ultimately, to facilitate better patient access, CGT developers will need to scale-up and manufacture their therapies in the most sustainable manner.
• Marie Jourdan, Director of Product Management, Donaldson Life Sciences, Bioprocessing Division

Ensuring that CGTs are scientifically innovative and commercially viable
Investment difficulties, marketing withdrawals, and safety issues rocked the CGT sector in 2024. However, 2025 offers a glimmer of hope; falling inflation, investment streams are flowing, and numerous CGTs will seek marketing authorization, and new technologies may enable commercial manufacturing. However, CGTs need to be innovative to secure investment, and developed as commercially viable medicines. Developers will need more than before strong clinical data emphasizing safety and efficacy, clearly demonstratable commercial benefits with a justifiable reimbursement strategy, and a sustainable, commercially viable CMC strategy.

We predict a geographic shift in CGT activity toward Japan. Much of the CGT sector is in clinical development, with much of European activity occurring in the UK. For 2025, the British investigational CGT manufacturing community may struggle with an under-resourced and unpredictable MHRA, sending sponsors elsewhere. Meanwhile, the PDMA in Japan is promoting its clinical support, and accepting early phase data from the West.
• Drew Hope, Senior GMP Compliance Consultant and Qualified Person, eXmoor Pharma and Lee Markwick, Senior CMC Translation Consultant, eXmoor Pharma

Attracting venture capital funding
One of the biggest challenges facing the cell and gene therapy market in 2025 will be addressing manufacturing cost-effectiveness to attract venture capital funding in an uncertain economic landscape. While venture capital in biotech has been on the rise, investors are less bullish than they were during the pandemic era and are seeking out companies with more clinically validated therapeutic pipelines that are viewed as 'safer bets.' The relative newness of cell and gene therapy, coupled with sector-specific hurdles such as scalability, has resulted in the CGT market not experiencing as significant an uptick in investment. We expect to see a continued push for the development of allogeneic cell therapies, which provide the opportunity for large-scale manufacture through scaling up, rather than autologous cell therapies, which necessitate scaling out production.
• Maddie Lawhorn, Process Engineer, CRB

Access to resources in a highly competitive environment
With the recent uptake on funding availability following the post pandemic funding contraction innovators and startups will need to find nimble ways to accelerate progression of their CGTs in order to retain competitiveness. Access to cost-effective labs and facilities, as well as trained professionals could prove difficult in a highly competitive environment requiring a high degree of specialization. The ability to secure such access will make or break many startups and together with them the ability we have to innovate in CGT and bring new therapies to patients.
• Eleonora Casucci, VP, Quality and Compliance, ProPharma

Sustaining momentum  
2024 was a record year for approvals in the cell and gene therapy space, and if current trends continue, the pace of approvals is poised to accelerate in 2025. One challenge will be to sustain this momentum. This will require flexibility on the part of manufacturers, in at least two different scenarios. In the first, developers with products at the preclinical stage will be incentivized to advance their products to early-phase trials, which may involve process scale up or transfer from an academic setting to a CDMO. In the second scenario, products already in early-phase trials will be moving to later-phase and commercial production, which in many cases may necessitate additional process scale up or a shift in manufacturing site. In both scenarios, manufacturers must have the flexibility to rapidly and efficiently adapt manufacturing strategies to maintain the delivery of these cutting-edge products to the patients who urgently need them. 
• James J. Cody, Ph.D., Associate Director, Technical Evaluations, Charles River

Technology and innovation

Risk-averse mindsets when it comes to technology
One of the biggest challenges facing the CGT industry is the current handicapping of novel technologies that could dramatically improve the speed, scalability, and quality of therapeutic development. In the long run, these technologies could ultimately broaden access to therapeutics by delivering cost savings across the value chain from development through commercialization. While manufacturing innovations have been developed, their impact has remained underwhelming due a mitigation mindset among therapeutic developers who are, understandably, seeking to avoid as much regulatory risk as possible. The trial and adoption of inventive process solutions will require a shift in mindset by therapeutic developers that could be further bolstered through pragmatic regulatory policy changes. In an industry with an insatiable appetite for therapeutic innovation, it is past time for the same hunger to fuel giant leaps forward in manufacturing capabilities to support the next generation of medicines and ultimately enable patient access around the globe.
• Kelli M. Luginbuhl, Ph.D., Co-Founder and General Manager, Isolere Bio by Donaldson

Portal-fatigue from a lack of standardized orchestration platforms
2025 will see the continued acceleration of the CGT industry, thus the need to increase productivity and efficiency. For new entrants and rising competitors that are looking into cellular orchestration solutions (software that tracks, manages and coordinates patient journeys for CGTs), this poses a major challenge. While the sponsors' needs may still be simple and basic, the needs of the other stakeholders in the CGT supply chain are highly complex. Consequently, building a solution that delivers value and a competitive edge in a cost-effective manner is increasingly more challenging. In addition, the multitude of available cellular orchestration platforms (COP) is causing ‘portal-fatigue’ for users who are required to regularly use 20 portals or more. The sector should consider standardizing on a commercially available solution to reduce the burden to users by offering a consistent and familiar user interface. 
• Antonios Spanos, Industry Advisor, TrakCel Consulting Services

Aligning and managing advancements
While the number of products progressing through early development, clinic and into commercial is increasing overall, we are still working in a relatively new and evolving field. If we consider the rate of advancement within academia, manufacturing, regulatory, health care systems and finance, it’s clear that some areas are moving much more quickly than others. A challenge presents itself when we look at the work that is required to align and harmonize across these different entities and avoid some of the costly and time-consuming delays that are still common in the sector. Delivery of treatments to patients is always the focus and to fully realize the potential of CGT therapies, communication and collaboration is critical. Alignment and pro-active management of technological advancement across all stages of the product life cycle will help address key challenges related to cost and timelines while also providing rapid and reliable delivery of products to patients. 
•Andrew Frazer, Ph.D., Associate Director, Scientific Solutions, Charles River 

Overcoming non-viral delivery barriers
If looking at the CGT sector through specifically a non-viral lens, the biggest upcoming 2025 challenge is the demonstration of intravenous extra-hepatic delivery of LNPs in order to fully realize the potential of these non-viral vectors across in vivo gene therapy and genome editing applications.
• Elizabeth Figueroa, Ph.D., Senior Consultant, Dark Horse Consulting

Read further insights on challenges related to:

• Scalability, supply chain and manufacturing (Part 2)
• And definitely don’t miss: Thoughts from our editorial advisory board