Moderna (MRNA) Status Update summary

Clinical Data and Efficacy

• Three-year follow-up of mRNA-4157 (V940)/INT plus pembrolizumab in high-risk melanoma showed a 49% reduction in recurrence and 62% reduction in distant metastasis risk versus pembrolizumab alone.

• Recurrence-free survival at 3 years was 74.8% for the combination versus 55.6% for pembrolizumab alone (HR 0.51, p=0.019).

• Distant metastasis-free survival at 3 years was 89.3% for the combination versus 68.7% for pembrolizumab (HR 0.384, p=0.015).

• Overall survival at three years showed 96% alive in the combination arm, with a hazard ratio of 0.425 and fewer events (3.7% vs 10.0%).

• Efficacy was consistent across biomarker subgroups, including TMB, PD-L1, ctDNA, and HLA status.

Safety and Tolerability

• The combination demonstrated a stable, manageable safety profile, with no increase in serious or immune-mediated adverse events compared to control.

• Most adverse events were grade 1-2, with fatigue, injection site pain, chills, and pyrexia most common.

• No potentiation of immune-related adverse events was observed compared to pembrolizumab alone.

Biomarker and Translational Analyses

• ctDNA analysis revealed benefits for both high- and low-risk patients, with molecular responders doubling compared to pembrolizumab alone.

• No significant association between individual HLA alleles and RFS was observed.

• ctDNA molecular non-responder patterns were associated with the highest frequency of recurrence events.