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When immuno-oncology programs fall short in translation, it is often because the models used upstream do not reflect the biology that developers ultimately care about. That gap is central to the work of Sanne Holt, Associate Director Immuno Oncology at Ncardia. Her role sits at the intersection of assay design, iPSC biology, and the operational realities of drug development.
A Career Built Inside the Realities of Translational Immunology
Holt’s path into oncology began at GSK, where work in the cell therapy unit showed her how hard it was to generate reliable in vitro insight. Primary cells were biologically authentic but operationally fragile. At Charles River, she saw the CRO perspective; at Merus, she experienced the tighter decision cycles of biotech. Different environments, same conclusion: the model ultimately determines the confidence you can place in the data.
Why Ncardia Offered a Practical Rather Than Conceptual Shift
Joining Ncardia gave Holt something new. Instead of adapting assays around the limitations of primary cells or donor availability, she could begin with iPSC-derived cells produced under controlled conditions, at scale, with consistent phenotypes.
“iPSCs are the next step in in-vitro safety testing,” she said, reflecting her view that reproducibility is a prerequisite for meaningful IO assays.
This alignment, technical and operational, made Ncardia a natural fit for building a new IO offering.
Why iPSC Models Matter in Immuno Oncology
Many IO programs still rely on a mixture of animal data and primary cell studies. Both have value, but their limitations are well-documented. Species differences can obscure safety signals. Donor variability confounds interpretation. Some tissues simply cannot be sourced consistently.
Compared to these systems, iPSC models provide controlled differentiation, large homogeneous batches, and dependable behaviour across experiments. With iPSCs, results are very steady and reproducible. This is vital when comparing multiple candidates or studying subtle functional effects.
Introducing Ncardia’s iPSC-Based Immuno Oncology Safety Panel
Holt’s most visible contribution so far is the development of Ncardia’s seven-tissue functional safety panel, designed to detect early off-target and functional liabilities for antibodies, ADCs, and cell therapies. Unlike expression profiling or fixed-tissue binding screens, this platform measures functional consequences across multiple human-derived tissues, a capability that traditional models rarely offer.
“As far as I’m aware, we are the first ones in the industry that offer a safety tissue screen across the major organs of the body,” she said.
To validate it, Holt’s team stress-tested the system with commercially available ADCs at high doses to confirm that subtle cytotoxic effects could be identified. This was not about simulating clinical exposure but proving that the panel can detect biologically meaningful changes when needed.
Managing Variability
Holt is careful not to describe the IO panel as automatic. Some iPSC lines differentiate cleanly; others require process optimisation. A small percentage fail. Assay readouts depend heavily on the quality of the therapeutic product; low viability in cell therapies, for example, can distort results without proper controls.
For her, discipline is part of the scientific method. Good data comes from well-defined questions, appropriate markers, and controlled readouts. Under her direction, Ncardia’s IO assays are built around this principle: ask the right question, measure only what is needed, and apply structure that supports reproducibility.
What IO Developers Are Trying to Solve Right Now
There is a clear trend among sponsors. As FDA guidance evolves and in-vivo models face scrutiny, companies are seeking reliable human-relevant data but remain unsure how to integrate these assays into their development pipeline. As she puts it, “What do I need to do, what are the right models to run, and how do I avoid doing too much or too little?” The challenge is balancing efficiency with completeness: not performing unnecessary studies, but also not omitting data that regulators or internal governance might require.
Where the IO Platform Goes from Here
Holt expects the safety panel to expand as more iPSC lines become available and as IO readouts diversify. Some tissues remain under development in the iPSC space; others may be added once reliable differentiation protocols are established.
Her goals are practical: improve predictiveness, reduce reliance on animal models where appropriate, and support earlier, clearer decision-making. She sees the platform as a way to catch avoidable risks earlier and prevent programs from moving forward on misleading signals.
For teams navigating similar challenges, Holt will discuss her latest data and workflows in an upcoming webinar, covering Ncardia’s multi-tissue safety platform and early cardiac risk assessment.
A Message for Teams Considering Human-Relevant IO Models
All in all, she does not frame iPSC adoption as an all-or-nothing choice. But she does encourage teams to build experience early.
“You need the right question, the right assay, and the right controls,” she said. Her emphasis is not on expansion but on intentional use, models that align with biology, and decisions that align with real data.
For Ncardia, Holt’s leadership brings a way of thinking about IO work that resonates across pharma and biotech: a focus on reproducibility, functional relevance, and a recognition that human biology is not the endpoint; it is the starting point.