A recent LinkedIn article by Stefano Gaburro, PhD, raises an important question for drug developers: under what conditions could a NAM-supported, or even NAM-only, IND be accepted?
The answer is not as simple as “animal studies are no longer needed.” The more useful takeaway is this: regulatory expectations are changing, and human-relevant models are becoming a more strategic part of early development planning.
For sponsors working with modalities that already have established safety knowledge, this shift could be especially meaningful.
Many development programs are not starting from zero. A sponsor may be optimizing an AAV capsid, modifying a known therapeutic platform, evaluating a structurally related compound, or developing a combination therapy where the individual components already have established safety profiles.
In these cases, the key regulatory question may not be: “Can we prove everything again from the beginning?”
It may be: “Can we show that this modification, combination, or platform application does not introduce a new safety signal?”
That is where NAMs can become highly valuable.
As Christy Holt, VP of Marketing and Sales at iXCells, notes, combination therapies are a strong example. When individual components already have established safety profiles, NAM data showing that the combination does not create new safety concerns may help support an IND strategy without requiring a full set of new animal studies.
The same logic may apply to other platform-based approaches. For example, AAV capsid optimization or other modality improvements may be supported by existing class or platform knowledge, while human biological models help evaluate what has changed.
For development teams, the impact could be significant.
A stronger NAM package may help shorten development timelines, reduce cost, and support faster IND acceptance when the data are scientifically justified and aligned with regulatory expectations.
This is not about replacing scientific rigor. It is about generating more relevant evidence earlier.
Human iPSC-derived models, organoids, gene-edited disease models, and other advanced in vitro systems can help sponsors evaluate biology in a context that is closer to the patient. These models can be used to assess mechanism, target engagement, toxicity risk, off-target effects, and therapeutic response before advancing into more expensive and time-sensitive stages of development.
For programs where prior animal and human safety data already exist, NAMs can help fill specific gaps rather than repeat work that may not add meaningful value.
The regulatory path is still case-specific. NAM data must be matched to the right context of use, the right biological question, and the right endpoint. A model that is useful for one safety question may not be appropriate for another.
That makes model selection critical.
Drug developers need human-relevant systems that are well characterized, reproducible, and aligned with the scientific question they are trying to answer. For some programs, that may mean scalable iPSC-derived cell models. For others, it may mean CRISPR-edited isogenic controls, patient-derived disease models, organoids, or assay-ready cells designed for screening and translational studies.
The opportunity is not simply to use NAMs. It is to use the right NAMs for the right question.
The movement toward NAM-supported INDs represents a practical shift in how development teams can think about preclinical evidence.
For platform technologies, optimized modalities, and combination therapies, sponsors may have an opportunity to build a more focused data package around human biology, existing safety knowledge, and clearly defined risk questions.
That could mean shorter development timelines, lower costs, and a more efficient path toward IND-enabling decisions.
At iXCells, we see this as an important moment for human-relevant preclinical research. As regulatory frameworks continue to evolve, the ability to generate reliable, disease-relevant human model data will become increasingly valuable for teams working to move therapies forward.
Author:
Christy Holt
VP of Marketing and Sales
iXCells Biotechnologies
With over a decade of experience in cellular biology and preclinical research, iXCells delivers human-relevant models that help researchers improve predictability and move new therapies forward.
