Objective, quantitative assessment of preclinical model translatability for IND-03

IND-03 proposals are evaluated on their ability to improve predictivity and reduce translational failure, with reviewers closely examining whether preclinical models are fit-for-purpose, human-relevant, and selected using transparent criteria. A common weakness identified in evaluations is reliance on qualitative or precedent-based model choice without objective, quantitative justification.

We contribute a platform for quantitative, mechanistic assessment of human relevance and translatability of preclinical disease models. Our approach compares animal models and NAMs to human molecular and pathway-level data in a perturbation- and intervention-specific manner, translating complex biological comparisons into explicit, comparable relevance scores.

Within an IND-03 consortium, we support:

• Objective justification of model selection, replacing narrative arguments with quantitative evidence

• Comparison and ranking of models for a defined context of use

• Identification of mechanistic gaps that limit predictivity and contribute to translational risk

• Transparent discussion of model limitations, aligned with reviewer expectations

• Strengthening of claims on improved predictivity and robustness of preclinical pipelines

Where relevant, these quantitative assessments can inform clear progression criteria and risk-mitigation strategies, while keeping the primary focus on scientifically defensible model choice.

From an evaluation perspective, our contribution strengthens:

• Excellence, through methodological rigour and reproducibility

• Impact, by credibly underpinning claims of reduced attrition

• Implementation, by clarifying the scientific rationale for key model-related decisions

Overall, we help turn translatability from an assumed property into a measured scientific parameter, directly addressing a central evaluation risk in IND-03 proposals and increasing the likelihood of a successful application.