Cell and gene therapy has matured into a global industry, but many of its core development challenges remain unchanged. From early regulatory uncertainty to today’s questions around manufacturing and dose selection, the path from preclinical research to the clinic is rarely straightforward. Janneke Meulenberg has experienced this evolution from the inside, starting with one of the first approved gene therapies and continuing with new vector platforms entering development today. Her perspective offers a practical look at how advanced therapies move from concept to patients.
When Gene Therapy Had No Playbook
When Janneke began working on Glybera in the early 2000s, gene therapy development was still largely unexplored territory for regulators and companies alike. Only a handful of organizations were working in the space, and the regulatory framework was minimal.
“There were hardly any guidelines, and those available were very, very high-level guidelines.”
That lack of structure meant developers were not simply following established regulatory expectations. They were helping define them. The development team at Amsterdam Molecular Therapeutics relied heavily on early dialogue with regulators while building their development strategy.
“It was really pioneering,” she says. “But that’s also the excitement that you get from working on these products.”
Those interactions shaped both the clinical development program and the manufacturing processes for AAV gene therapy. The company also expanded rapidly during that time, growing from a small founding team to around one hundred employees by the time she left.
For developers today, the regulatory landscape is more defined. But the experience of the early programs still highlights a basic principle of advanced therapy development: close engagement with regulators from the start.
Manufacturing Is Still a Central Constraint
Despite advances across the field, Janneke sees manufacturing as one of the persistent challenges in gene therapy development.
“I think manufacturing is still a challenge,” she says, particularly when companies work with vector systems that regulators are less familiar with.
For commonly used platforms such as AAV, the expectations for production and quality are now better established. But when a program introduces a new vector system, much of the development work must again focus on defining what reasonable manufacturing requirements should look like.
That is the situation her team faces at Nimvec Therapeutics, which is working with an SV40-based vector platform. The vector has not previously been tested in humans, which means development programs cannot rely entirely on existing precedents.
In these situations, manufacturing development is closely linked to regulatory dialogue. The technical work involves not only building a production process but also explaining how that process compares to more established viral vector platforms.
For developers building new vector technologies, manufacturing development therefore becomes both a technical and strategic exercise.
About Janneke Meulenberg
Janneke Meulenberg is a biotechnology executive with a background in biochemistry, a PhD in molecular genetics and Masters in Business Administration. Over the course of her career, she has worked across public companies and startups focused on advanced therapies, particularly virus-based products and gene therapies.
She was part of the founding management team of Amsterdam Molecular Therapeutics, later uniQure, where she steered development of Glybera, the first AAV gene therapy approved in the Western world. Her work there spanned process development, clinical development, regulatory interaction, and the growth of the company from a small founding team to a publicly listed organization.
She has since served in senior leadership roles across multiple biotech companies working on oncolytic viruses, vaccines, and gene therapies. After leading the European site of the NASDAQ-listed company MeiraGTx, she established her own venture and now works on a fractional C-level basis with several companies, including Nimvec Therapeutics, which is developing a novel viral vector platform for diabetes.
For developers entering cell and gene therapy today, Janneke’s career traces much of the field’s early development. Her perspective combines the experience of building one of the first approved gene therapies with the practical realities of bringing new viral vector platforms toward the clinic.
The Problem of Dose Translation
Another challenge that remains unresolved across many gene therapy programs is determining the correct dose when moving from preclinical studies into first-in-human trials.
“The challenge always is the dose translation from animals or cells to the human study,” Janneke explains.
Animal models often only partially reflect the human disease they are meant to represent. In gene therapy, an additional complication arises from differences in how viral vectors enter cells across species.
Because vector uptake can vary significantly between animals and humans, dose predictions based on preclinical models are inherently uncertain.
That uncertainty carries practical consequences. Many gene therapies cannot be administered repeatedly, meaning the first dose used in clinical trials needs to be carefully selected.
“You don’t want to waste your patients’ time with a dose that’s not effective,” she says.
Developers therefore face a difficult balance. They must begin clinical testing with a dose low enough to be safe, yet high enough to demonstrate meaningful biological activity.
Nimvec Therapeutics (formerly Amarna Therapeutics)
2008
Leiden, Netherlands
Development of viral vector–based gene therapies, including an SV40-based vector platform being developed to induce immune tolerance to insulin for diabetes.
When Development Decisions Have No Perfect Answer
Even with careful planning, development programs often reach decision points where the available data does not provide a clear path forward.
Janneke recalls one such moment during the development of Glybera. The company had created a more scalable production system for the therapy and wanted to transition to it before entering clinical trials. However, a critical experiment designed to confirm efficacy with the new process failed.
The team could not determine the cause of the negative result, and repeating the experiment would have required another year due to the breeding cycle of the animal model.
Ultimately it was decided to move forward with the original production system for the first clinical study, even though it was less efficient.
It was a difficult choice that required weighing technical uncertainty against development timelines and financial risk. But the decision allowed the company to enter clinical trials sooner while continuing to improve the manufacturing process later.
Such moments, Janneke notes, are common in biotechnology development. Biological systems do not always behave predictably, and even carefully controlled experiments can produce results that remain unexplained.
What Young Biotech Founders Often Overlook
After decades in advanced therapy development, Janneke sees a consistent pattern in the mistakes made by early-stage biotech founders.
“I think young biotech entrepreneurs are overly optimistic about how long it takes to develop a drug,” she says.
The challenge is not only the duration of development but also the complexity of the supporting work required. Academic researchers entering biotechnology often focus primarily on experiments and scientific results. However, regulatory development requires an equally strong emphasis on documentation, traceability, and strategic planning.
A regulatory submission includes data collected over many years. That means the origin and history of key materials, such as production cell lines, must be carefully documented from the beginning.
Entrepreneurs who overlook these requirements can create problems that surface much later in development.
For developers building new programs today, the lesson is simple but often difficult to apply: strong science is necessary, but it is not sufficient. Successful development programs combine scientific insight with disciplined operational planning from the earliest stages.
Why Janneke’s session matters
Many developers entering cell and gene therapy today are building on a field that did not yet exist twenty years ago. Janneke Meulenberg helped shape some of the early regulatory and manufacturing frameworks while working on Glybera, the first AAV gene therapy approved in the Western world. At Future of CGT, her session connects those early lessons with the challenges developers still face today, including new vector technologies, manufacturing strategy, and the difficult decisions that determine whether a program reaches the clinic.
