Advance

Advance™ is a technology-enabled service from Instem designed to help pharmaceutical researchers conduct comprehensive carcinogenicity risk assessments in alignment with the ICH S1B Weight of Evidence (WoE) Addendum. By leveraging six specialized, expert-built modules that correspond directly to the six guideline-defined factors, Advance enables research and development teams to rapidly produce regulator-ready WoE dossiers — potentially eliminating the need for costly and time-consuming two-year rat carcinogenicity studies.

Advance is aimed at safety professionals, drug development researchers, and R&D organizations seeking to streamline early-stage safety evaluations, reduce reliance on animal testing, lower development costs, and accelerate time to market. The service integrates seamlessly into existing in-house workflows and can be applied at any stage of the drug discovery and development process.

Key Benefits

• Saves Time: Advance can reduce time to market by 3–5 years by enabling researchers to avoid lengthy carcinogenicity testing programs. The service fits into existing workflows to further minimize delays.
• Reduces Reliance on Animal Testing: Advance supports adherence to the 3Rs principles — Replacement, Reduction, and Refinement — helping organizations align with the growing movement to minimize animal use in research.
• Expert-Led: The service was designed by specialists with hands-on ICH S1B framework experience, ensuring scientific robustness, regulatory alignment, and grounding in real-world drug development needs.
• Lowers Costs: By eliminating the need for multi-year carcinogenicity studies, Advance can save researchers an estimated $2–$4 million per program.
• Scalable: The Advance dataset grows alongside in-house data and publicly available sources, becoming increasingly comprehensive as development progresses through each stage.

Core Modules

• Target Biology: Evaluates whether the drug target has a known role in tumor development by integrating expression profiles, pathway analysis, and translational evidence from human and animal data to assess oncogenic potential.
• Secondary Pharmacology: Assesses off-target interactions using in vitro binding assays and computational predictions to identify unintended pharmacological effects potentially linked to tumor development.
• Histopathology: Identifies hypertrophy, hyperplasia, inflammation, foci of cellular alteration, and preneoplastic changes, providing critical insight into tissue-level responses to drug exposure and potential carcinogenicity.
• Hormonal Perturbation: Covers microscopic changes and organ weight shifts in endocrine and reproductive tissues to identify disruptions in hormonal balance that may lead to reproductive or developmental toxicity.
• Genotoxicity: Integrates genetic toxicology data from in vivo assays, including micronucleus and comet assays, to determine a substance's potential to cause DNA damage — a key factor in carcinogenic risk evaluation.
• Immune Modulation: Extracts immune-related endpoints from laboratory results and custom domains to assess potential immunosuppressing and immunoenhancing effects.

How Advance Works

1. Advance can be implemented at any stage of the drug discovery or development process, offering flexible deployment across one or all six WoE modules.
2. Automated data mining integrates with in-house data, delivering rapid insights from complex inputs and significantly reducing the time required compared to manual data collection.
3. As new studies are conducted and data is generated, it is continuously added to a growing, regulator-ready dossier.
4. Instem's expert scientific team collaborates closely with clients to review, interpret, and finalize comprehensive WoE summary documents ready for regulatory submission.

Regulatory Alignment and Integration

• Advance is fully aligned with the ICH S1B WoE directive and produces industry-approved reports suitable for regulatory submission, including to agencies such as the FDA.
• The solution can be run as a full six-factor assessment or focused on individual modules to complement existing in-house processes.
• A real-world case study demonstrated that Instem's Drug Target Carcinogenicity Risk Assessment, delivered in collaboration with a pharmaceutical client, supported a WoE summary submitted to the FDA that resulted in an accepted supplemental NDA and successful market launch within approximately one year of engagement.

Advance is delivered as an expert-led service by Instem, with the scientific team providing support throughout the entire assessment process to ensure evidence dossiers are complete, accurate, and submission-ready. The solution is part of Instem's broader In Silico & Data Insights portfolio and is suitable for organizations at any stage of drug development seeking to leverage technology-enabled approaches to safety assessment.