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Mitigating Immunogenicity Risk in Biologics & Gene Therapies: Best Practices & Case Examples

Why Immunogenicity Matters

Biologics and gene therapies hold enormous promise for treating complex diseases, but their success can be derailed by one critical challenge: immunogenicity. When the body’s immune system recognizes a therapeutic protein, viral vector, or other biologic component as “foreign,” it can mount an unwanted immune response. This may lead to reduced efficacy, adverse events, or even program-ending regulatory setbacks.

For sponsors developing innovative therapeutics, understanding and mitigating immunogenicity risk is not optional, it’s essential for progressing safely through the clinic.

Key Drivers of Immunogenicity

Several factors contribute to immunogenicity risk in biologics and gene therapies:

• Protein sequence and structure: Even small modifications can introduce novel epitopes that trigger an immune response.
• Formulation and delivery route: Excipients, aggregates, or delivery methods (such as IV vs. intramuscular) can influence immunogenicity.
• Patient population: Genetic background, disease state, and prior exposure to related therapies all affect risk.
• Viral vectors in gene therapy: Pre-existing immunity to AAV or other vectors is a common challenge.

Anticipating these factors early allows sponsors to design smarter development strategies.

Best Practices for Mitigating Risk

At InfinixBio, we recommend a layered approach that integrates scientific rigor with regulatory awareness:

1. Early In Silico and In Vitro Assessment
   Computational tools and cell-based assays can identify potential immunogenic epitopes before costly animal or human studies.
2. Robust Preclinical Immunogenicity Studies
   Carefully selected animal models, combined with validated assays, provide critical insight into immune responses.
3. Strategic Bioanalytical Method Development
   Fit-for-purpose assays—such as ADA (anti-drug antibody) assays, neutralizing antibody assays, and cytokine release tests—must be sensitive, specific, and validated to regulatory standards.
4. Biomarker Integration
   Monitoring biomarkers of immune activation and inflammation provides early warning signs of immunogenicity in preclinical and clinical studies.
5. Iterative Risk Assessment Across the Pipeline
   Immunogenicity evaluation should be ongoing, with data from preclinical studies informing clinical trial design and patient monitoring.

Case Example: Reducing Risk in a Gene Therapy Program

In a recent program, a sponsor developing an AAV-based therapy faced concerns about pre-existing immunity in their target patient population. By designing a customized immunogenicity testing strategy, including neutralizing antibody assays and cytokine profiling, our team identified subgroups of patients at higher risk.

These insights informed both inclusion/exclusion criteria and dosing strategy, helping the program advance to the clinic with a clearer risk profile and stronger regulatory support.

Why Choose InfinixBio

Our team brings deep expertise in bioanalytical assay development, immunogenicity testing, and regulatory strategy. With operational agility and end-to-end support, we partner with sponsors to design and execute immunogenicity strategies that de-risk development and accelerate progress toward the clinic.

Whether you’re developing a novel biologic or pioneering a gene therapy, InfinixBio provides the tools, insights, and experience to help you anticipate and mitigate immunogenicity risk.

Ready to strengthen your immunogenicity strategy?

Connect with InfinixBio today for a consultation and learn how we can help advance your program with confidence.