EpiVax Launches AI-Enhanced Analyses for Immunogenicity Prediction
Building on decades of leadership in computational immunology, EpiVax is introducing several AI-enabled enhancements to ISPRI™, its industry-leading in silico platform for assessing the immunogenicity risk of biotherapeutic sequences. The release introduces an updated JanusMatrix™ model, a refined tolerance-adjusted immunogenicity score, and an enhanced anti-drug antibody (ADA) prediction model designed to provide researchers with deeper insight into immunogenicity risk, supporting more informed asset management and development decisions.
Advancing Immunogenicity Prediction to Support Better Development Decisions
EpiVax has pioneered the field of immunogenicity assessment with computational approaches that identify and characterize T cell epitope density and tolerance potential to assess immunogenicity risk of biotherapeutic sequences. These analyses are executed in the ISPRI™ toolkit, which enables teams to assess intrinsic, sequence-based characteristics of primary biologic active ingredient and process- and product-related impurity sequences using extensively validated models.
Central to this work are EpiMatrix® and JanusMatrix™, complementary models within the toolkit that provide distinct insights into different features of sequence-derived immunogenicity risk. EpiMatrix identifies potential T cell epitopes and evaluates epitope content to help characterize the immunogenic potential of protein sequences, while JanusMatrix assesses patterns of cross-conservation with the human proteome to provide additional context for understanding immune tolerance.
As biologic therapeutics become increasingly complex, accurately characterizing immunogenic potential has become even more important—not only for selecting and optimizing development candidates, but also for asset risk management, guiding preclinical strategy, supporting bioanalytical planning, and providing valuable context for informing clinical immunogenicity strategy.
Analysis use cases range from in-depth characterization of individual candidates to high-throughput assessment of thousands of sequences for rapid ranking and downselection and beyond, with results generated in real time. This combination of speed, scalability, and biological depth provides a comprehensive understanding of sequence-derived immunogenicity risk across a wide range of analytical needs.
The latest model updates, just newly released in ISPRI, strengthen EpiVax’s best-in-class immunoinformatics capabilities by providing a comprehensive and holistic understanding of adaptive immune responses throughout the product lifecycle. Together, the enhancements represent the next iteration of the platform, reflecting EpiVax’s continued investment in cutting-edge R&D and leadership in computational immunology.
What’s New in ISPRI™
The release includes three major updates to ISPRI’s predictive capabilities, each addressing a different aspect of immunogenicity risk. While the updates provide value independently, they are designed to be interpreted together to provide a broader view of sequence-derived and clinical immunogenicity risk, helping streamline assessment and supporting more efficient development decisions.
JanusMatrix™ 2.1
JanusMatrix™ 2.1 builds on the original JanusMatrix concept by applying AI models trained on large-scale T cell assay datasets. This enhanced workflow weights human cross-conserved epitopes based on expression and prevalence patterns, providing a more accurate probability assessment of whether a given epitope will be tolerated by the immune system. The resulting tolerance profiles offer a detailed view of the biological relevance of therapeutic epitopes.
Understanding immune tolerance provides important context for interpreting immunogenicity risk. JanusMatrix 2.1 helps distinguish epitopes that may be more likely to stimulate an immune response from those that exhibit characteristics associated with immune tolerance. This enables researchers to generate more informative immunogenicity assessments that can guide candidate selection, sequence optimization, and interpretation of sequence-derived risk.
JanusMatrix-Adjusted EpiMatrix (JAX) Score
Leveraging JanusMatrix 2.1, EpiVax has introduced a new immunogenicity scoring system designed to align more closely with clinical immunogenicity outcomes. The JanusMatrix-Adjusted EpiMatrix (JAX) score brings the EpiMatrix and JanusMatrix concepts together into a singular datapoint, simplifying immunogenicity risk assessments of therapeutics. In addition, the JAX score extends the application of the previous Adjusted EpiMatrix score across all biological sequences.
By integrating tolerance insights into immunogenicity scoring, the JAX score provides a more clinically relevant framework for evaluating sequence-derived risk. This enables more meaningful comparisons between candidates while supporting prioritization, optimization, and other development decisions across a broad range of modalities.
ADA 2.2
EpiVax has also updated its clinical ADA prediction model for monoclonal antibodies with the release of ADA 2.2, an enhanced version of the ADA 1.0 model first introduced in 2013. The refined model combines epitope-based measures—including overall and foreign T cell epitope content—with antibody biophysical attributes and mode of action to provide a more complete assessment of clinical immunogenicity risk. Trained on an expanded dataset of diverse clinical mAbs, ADA 2.2 demonstrates a stronger correlation between predicted and clinically observed immunogenicity than previous versions. This improved predictive performance gives researchers greater confidence when evaluating immunogenicity risk and provides valuable context for bioanalytical and clinical strategy.
“Immunogenicity is shaped by multiple interacting biological factors, and no single measure can fully characterize risk. With this release, we sought to better account for that complexity and provide researchers with a more nuanced view of how a therapeutic may be recognized by the human immune system.”
— Guilhem Richard, PhD, Chief Technology Officer, EpiVax
A More Complete View of Immunogenicity Risk
Together, these enhancements strengthen ISPRI’s ability to characterize adaptive immunogenicity risk from multiple perspectives. By combining improved assessment of immune tolerance, sequence-derived risk, and clinical immunogenicity potential, the updated models provide distinct information that can be interpreted together to build a more comprehensive picture of product-specific development, regulatory, clinical, commercial, and valuation risk.
This broader perspective can help researchers identify potential liabilities, prioritize where further investigation or optimization is warranted, and make the most efficient use of development resources.
Aligned to New Approach Methodologies (NAMs) Emphasized by Global Regulatory Bodies for Human-Relevant Drug Development
These advances align closely with recent regulatory initiatives advancing the adoption of human-relevant methods in drug development, including the FDA’s 2025 Roadmap to Reducing Animal Testing in Preclinical Safety Studies and 2026 draft guidance, General Considerations for the Use of NAMs in Drug Development. As computational immunogenicity assessments continue to play an increasing role in biologic development, advances in predictive performance provide stronger biological context for evaluating risk, helping teams prioritize resources while complementing downstream experimental, bioanalytical, and clinical activities.
The latest ISPRI release marks a significant advancement in EpiVax’s approach to immunogenicity prediction, incorporating AI-enabled methods to more accurately reflect the biological complexity underlying immune response. By improving how immune tolerance and clinical immunogenicity potential are evaluated, these advances support a more defensible characterization of immunogenicity risk to give biologic developers greater confidence when making development decisions and preparing for regulatory discussions.
Learn more about the science behind ISPRI™ and how these advances can support your biologics program!
