What Early Developers Often Miss in Preclinical Work: Margot Pont’s Experience in CGT
Many cell and gene therapy programs start in academic laboratories with a strong focus on biology and mechanistic insight. Margot does not question that foundation, but she sees how easily key development questions remain in the background. Looking across projects in academia, biotech, and clinical-stage companies, she recognizes recurring patterns: models that do not represent the patient population, processes built on idealized donor material, and decisions postponed until changes become costly.
Her main observation for young teams is that many of these problems are predictable. As she puts it:
“Above all, it’s the lack of truly predictive models.”
If you recognise where preclinical work most often fails to translate, you can design studies and processes that reduce the need for major rebuilds later on.
Models, assays, and the limits of prediction
When Margot discusses preclinical strategy for cell therapy, she tends to start with the model rather than the assay. Assays can be carefully optimised and produce convincing results, yet still sit on models that do not reflect clinical variability. Donor material behaves well and is relatively easy to obtain. Patient material, particularly in advanced disease, rarely behaves in the same way.
This gap affects how you interpret your data. A strong in vitro result on donor cells is often taken as a sign that a construct will perform equally well in patients, while the impact of process variation is underestimated once the starting material shifts from healthy to diseased. Margot summarises that underlying issue sharply:
“You have enormous donor and patient heterogeneity, and that heterogeneity is part of your product.”
Margot has seen program move forward on the basis of apparently solid preclinical packages, only to encounter difficulties when entering clinical manufacturing. For her, the issue is not that preclinical studies lack value, but that their constraints are often left implicit. If you make those limits explicit earlier and not over-interprete their meaning, you give yourself more control later.
About Margot Pont
Margot Pont has built her career around moving cell therapies from early research into first-in-human studies. She studied Biomedical Sciences in Leiden, completed a PhD in cell therapy at the LUMC, and has worked on CAR T and other cell therapy programs in Europe and the United States. Across roles in academia and biotech , she has been close to the point where scientific ideas either progress toward the clinic or stall.
At Integra Therapeutics, Margot focuses on early development strategies and how experimental design, process development, and regulatory expectations fit together. At the Future of CGT event, she will speak in the session on preclinical reality, sharing lessons that are directly relevant if you are building an early cell or gene therapy program.
“There is an underestimation of how a process behaves with patient material compared to donor material.”
Bringing process development into the picture earlier
A second pattern she frequently encounters is the separation of preclinical and process development work. Teams often treat process development as a follow-up activity that starts once the main biological questions appear resolved. For cell therapies, this separation is risky because the process largely defines the product.
If all stimulation, culture, and expansion work is optimized on robust donor material, you can end up with an overly optimistic view of your product. Margot’s wording here is very direct:
“There is an underestimation of how a process behaves with patient material compared to donor material.”
When the first batches from patient material enter the same process, fragility and variability become visible and force repeated optimization.
So if you are making construct decisions now, it is worth asking, each time: what will this look like in a realistic manufacturing setup, with patient material, not just donor material?
About Integra Therapeutics
Integra Therapeutics, founded in 2020 in Barcelona, develops next-generation gene writing tools to improve the efficiency and safety of advanced therapies. Its lead platform, FiCAT, is designed to address current limitations in gene writing, specifically size, precision, and stability. FiCAT combines the precision of CRISPR-Cas with the transfer efficiency of an engineered piggyBac transposase, enabling targeted insertion of small and large DNA payloads into the genome of patient cells .
The company operates in an area where platforms are still emerging, yet already need to be developed with the same rigor as any therapy on a path to patients. If you are building in CGT, this is the tension you will recognize: early decisions feel reversible, until they are not.
Integra Therapeutics
2020
Barcelona, Spain
FiCAT, a gene writing and targeted integration technology for cell and gene therapy development
Using public regulatory information as a design tool
For many early CGT groups, regulation feels distant and opaque. Margot takes a more practical view. Assessment reports and review documents for recently approved products are publicly available and show which data regulators considered sufficient, where they requested clarification, and which aspects attracted critical questions.
In her words:
“All the documentation, the assessment reports from the EMA, the FDA… you can extract a great deal from them about how the agencies look at certain issues.”
If you use these documents early, especially in modalities with several approved products, you can form a realistic sense of what “good enough” looks like and address avoidable gaps in your future dossier.
Decision making under uncertainty
Margot also sees how research habits influence development decisions. Researchers are trained to delay conclusions until they have gathered as much data as possible. This caution is appropriate in fundamental science, but it can slow development when every additional experiment adds time without changing the decision that has to be made.
She therefore distinguishes between reversible and irreversible decisions. Reversible decisions can often be taken earlier with the understanding that they can be adjusted later. Irreversible decisions, such as committing to a manufacturing platform, deserve more preparation but still need to be taken without complete certainty. Her reminder is simple and uncomfortable:
“Not making a decision is also a decision.”
If you wait indefinitely for perfect information, you are still choosing. The question is whether that choice improves your risk profile, or only slows down your timeline.
Seeing development through the patient’s eyes
For Margot, understanding what a therapy looks like from the patient’s perspective is an essential part of development. A simulated patient journey for a CAR T program, following each step from referral to leukapheresis, hospital stays and post treatment monitoring, highlighted aspects of burden and logistics that are not obvious from protocol documents alone.
She notes that scientists often intend to think with the patient in mind, yet the practical implications of design choices are easily overlooked. The frequency of hospital visits, the points in the pathway that create the highest stress, and the possibilities to move parts of the process closer to home can all influence whether a therapy is acceptable and feasible in practice. Her advice is explicit:
“Truly bring the patient perspective into what you are doing.”
Why Margot’s session matters
In the Future of CGT session on preclinical reality, Margot will bring these strands together. Her contribution is based on recurring challenges she has observed when programs move from academic promise to clinical implementation. If you are an early CGT team, her perspective gives you a practical way to test assumptions and prioritize work. It helps you decide where to invest effort before you commit major resources, how to balance speed and rigor, and how to integrate the patient journey into technical planning. Above all, it treats translation as something you build into experiments and decisions from the beginning, rather than as a separate stage that starts once the biology appears to work.
“Truly bring the patient perspective into what you are doing.”
