Castle Biosciences (CSTL) Status update summary

Clinical context, test overview, and validation

• DecisionDx-Melanoma is a 31-gene expression profile test for Stage I-III melanoma, providing independent risk stratification for sentinel lymph node positivity and recurrence, supplementing traditional clinicopathologic factors.

• The test outputs i31-SLNB (sentinel lymph node positivity risk) and i31-ROR (recurrence risk), integrating gene expression with clinical variables for precise risk prediction.

• DecisionDx-Melanoma has demonstrated clinical validity and utility in multiple retrospective, prospective, and real-world studies, with robust risk separation and prognostic value beyond traditional factors.

• Patients tested with DecisionDx-Melanoma showed a 32% lower 3-year melanoma-specific mortality rate compared to untested patients.

• The test is validated in over 58 peer-reviewed publications and is associated with improved survival.

DECIDE study design and objectives

• The DECIDE trial is a prospective, multicenter study evaluating the clinical utility of i31-SLNB in guiding sentinel lymph node biopsy (SLNB) decisions.

• Primary objectives: confirm i31-SLNB's predictive performance, assess its real-world impact on SLNB decisions, and track recurrence outcomes in patients with <5% predicted nodal risk.

• Enrolled 912 patients, median age 65, with a broad range of melanoma thickness and clinical features, reflecting real-world practice.

• The study prospectively confirmed the performance of i31-SLNB in predicting SLN positivity and guiding SLNB decisions.

• The test identified low-risk patients well below the 5% NCCN threshold and high-risk patients with up to 13x higher SLN positivity.

Key findings and clinical impact

• i31-SLNB stratified patients: 52% had <5% predicted nodal risk, 32% in the 5-10% range, and 16% >10%.

• In Stage IB (T1b/T2a), node positivity was 1.4% for low-risk and 18.5% for high-risk, a 13-fold difference, enabling precise identification of patients who can safely avoid SLNB.

• Across all stages, node positivity rates were 2.6% (<5% risk), 7% (5-10%), and 21.4% (>10%), confirming strong risk discrimination.

• Low-risk patients who skipped SLNB had a 97.8% three-year recurrence-free survival, supporting safe de-escalation of care.

• Compared to other GEP tests, DecisionDx-Melanoma provided superior risk stratification, especially in T1b-T2a tumors.