DDW’s Megan Thomas spoke with industry experts about their predictions for drug discovery opportunities in 2025. Previously, with a focus on technology, machine learning (ML) and artificial intelligence (AI), as well as neuroscience and cancer research. Here, looking at cell and gene therapy.

For the last few years, the cell and gene therapy (CGT) sector has been included on prediction lists as the sector continues to expand. In August 2024, PartnerRe wrote that there are currently over 500 therapies in various stages of development, and it is anticipated that by 2025, the FDA will approve an additional 10 to 20 gene and cell therapies¹.

Mike Kelly, President and Chief Executive Officer of NervGen

NervGen’s Mike Kelly weighed in on CGTs in relation to neuroscience, which he believes will make continued strides, driving more effective and personalised treatments for neurological disorders. He said: “These advances bring the potential to not only treat symptoms but also target the root causes of many neurodegenerative conditions.”

Natalia Elizalde Urdiain, Chief Business Development Officer, VIVEbiotech

Natalia Elizalde Urdiain said: “This year has been a record year for new cell and gene therapy approvals, with seven new therapies approved in 11 months. I expect this regulatory success will continue to drive the space to grow in new directions in 2025. In particular, development of lentiviral vector-based technologies are likely to increase, including in vivo gene therapies delivered directly to patients as vaccines, as well as in vivo CAR-Ts and for rare disease treatment. This would build on a rise in clinical trials utilising in vivo lentiviral vectors observed in 2024. Expansion of CAR-Ts to autoimmune disorders, lupus, type 1 diabetes, and additional conditions will bring hope to new patients. We also predict new cell therapies against solid tumours, exploring applications of sophisticated CAR-Ts and alternatives like TCR-T and TILs while using lentiviral vectors as gene transfer technologies, based on the ongoing discussions with our biotech and pharmaceutical company partners.

Josh Ludwig, Global Director Commercial Operations at ScaleReady

Josh Ludwig said: “The CGT sector continues to navigate the challenging landscape of reduced investor confidence and downsizing due to unsustainable business models, where 2024 has again seen many CGT companies cutting large numbers of staff or shuttering completely. The industry must adopt high-throughput solutions that enable efficient scale-up and scale-out to reach the many patients in need. Traditional models struggle with complexity and cost, but ScaleReady’s gas-permeable membrane technology solves this. In 2025, we expect acknowledgment that the adoption of such technologies is the only acceptable path forward to meet patient demand, delivering more efficient manufacturing processes that will expand patient access to life-saving therapies without compromising on quality or cost.”

Stella Vnook, CEO of Likarda

Stella Vnook weighed in that from hormone replacement to CGTs, sustained and targeted delivery can be the key to transforming a drug candidate from one that struggles in clinical trials to a safe, effective treatment that reaches the market. She said: “Hydrogel-based technologies are gaining attention for their ability to encapsulate biologics and small molecules, offering controlled release and holding them in place at the desired tissue site. These systems not only enhance site-specific efficacy but also reduce systemic toxicities. As biotech and pharmaceutical companies look to improve therapies and extend IP protection, 2025 promises to be a pivotal year for hydrogel encapsulation technologies.”

Lee Markwick, Senior CMC Translation Consultant, eXmoor Pharma

CGTs have faced numerous challenges of late, according to Lee Markwick. These include limited investment and withdrawal of approved therapies, alongside concerns over T-cell malignancy. However, he says: “2025 offers a glimmer of hope; inflation is decreasing, investment streams are beginning to flow, and numerous CGT are anticipated to apply for market authorisation. Furthermore, new technologies are becoming available to solve the challenges associated with commercial scale manufacturing. Therapy developers should focus on three essential areas to stand out from the crowd in 2025; strong clinical data emphasising safety and efficacy, a sustainable, commercially-viable CMC strategy and demonstrable commercial benefits with a justifiable reimbursement strategy.”

Jason Jones, Global Business Development Lead, Cellular Origins

Jason Jones commented that 2023/24 was the CGT’s sector’s second landmark year for approvals, but that 2025 is pivotal for manufacturing. He said: “With approvals in new indications and current therapies earlier in treatment lines, CGT must scale from producing 10-11,000 products in 2023 to >100,000 products in 2025. Just Multiple Myeloma BCMA CAR T therapies (Carvykti, now second line treatment) need to scale from 3-4,000 patients a year to 30-40,000, a single manufacturer to produce more CGT drug products than the entire industry in 2023. More of the same is unviable, so 2025 must see robotic industrialisation with technology like Cellular Origins’.”

Dr Brian Burke, Chief Commercial Officer, Tozaro

“CGTs are undeniably one of the most groundbreaking developments within our sector in recent times”, said Brian Burke. “With more treatments being developed every year, we’re now at a stage where we can prescribe a wealth of CGTs to patients for different conditions – potentially even before full presentation of pathology. However, it is essential that the industry works to further improve accessibility and affordability moving forward. Optimising manufacturing processes to drive new therapies to market faster and at a reduced cost is a key element of these efforts, and we see this emerging as a major focal point through 2025.”

Burke says that viral vector production and purification to facilitate delivery of genetic payloads is a significant technical and economic pain point. “Current approaches are costly and give low yields due to over reliance on processes developed for antibody manufacturing. Emerging technologies, such as chemically-derived affinity ligands, represent an exciting prospect to transform this area – offering increased yields, reduced manufacturing costs and the ability to rationally design reagents. This helps to tailor them to each application, rather than having to design new processes or make large adaptions around the reagent.”

By investing in crucial research to address important manufacturing bottlenecks like this, Burke thinks accessibility issues will be solved and life-saving treatments can be brought to all patients who need them.

Amanda Haupt, Business Unit Manager, Revvity

Haupt says that although base editing is still in its infancy, preclinical and early clinical data show enormous potential for its use for the generation of advanced stem cell therapies. “Compared to CRISPR-Cas9, base editors offer an improved safety profile and increased efficiency for the introduction of single nucleotide changes. Notably, base editing has also opened the door to potentially new therapeutic strategies, such as epitope masking by single nucleotide change, to make transplanted HSPCs resistant to cancer targeting drugs while retaining full cell functionality. Although not yet fully evaluated in the clinic, with convincing preclinical data, base editors are a promising candidate for creating the next generation of gene and cell therapies, especially in sensitive cell types such as stem cells.”

Erik Wiklund, CEO of Circio 

Current gold standard virus-based gene therapy faces substantial limitations in potency, repeat dosability and manufacturing cost, says Wiklund. “Advances in nucleic acid design, such as circular mRNA and stealth DNA vectors, will enable the field to move from viral vectors towards safer, cheaper, repeat-dosable formats. However, bringing the advantages of these novel nucleic acid systems to patients will require complementary delivery technology to efficiently reach specific target cells and organs.”

According to Wiklund, 2025 will be the year when exciting nucleic acid and delivery technologies converge to create novel therapeutic candidates to tackle devastating genetic diseases and bring the curative prospects of gene therapy to a broader patient population.

Pedro Echave, Senior Manager, Global Business Segment, Revvity

“The decreasing cost of sequencing combined with gene editing and modulation technologies, like CRISPR, will advance our understanding of non-protein-coding RNAs, which have regulatory functions in the cell”, says Pedro Echave. “RNA-sequencing is a well-known set of tools for assessing gene expression in any sample type including bulk tissues, body fluids, and cell samples. Multiple applications for RNA profiling have been developed, including the determination of gene expression at single-cell resolution and spatial transcriptomics. Additionally, a variety of non-coding RNAs such as microRNA and long non-coding RNA are also now routinely studied. However, most of these techniques focus on protein-coding RNAs.”

According to Echave, understanding how non-coding RNAs regulate disease can lead to the implementation of non-invasive, NGS-based tests to monitor or diagnose several diseases. He said: “Recently, profiling RNA in plasma (mRNA and microRNA) can detect early changes associated with breast cancer, melanoma, and cardiac arrhythmias. Additionally, a salivary microRNA signature has been recently shown to diagnose endometriosis in women with high accuracy. With thousands of published peer-reviewed articles showing correlation between RNA profiles and disease, and several clinical trials ongoing, we expect an increase in the number of RNA signatures that can be used in clinical practice. Analysing samples such as blood, urine or saliva will make disease detection and monitoring accessible, repeatable, and more patient-friendly.”

References 

1. https://www.partnerre.com/perspectives/the-future-is-now-reimagining-the-impact-of-gene-cell-therapies/#:~:text=Landscape%20and%20trends%20of%20gene%20%26%20cell%20therapies&text=There%20are%20currently%20over%20500,20%20gene%20and%20cell%20therapies