Moderna (MRNA) investor relations material

Pipeline and Program Updates

• The oncology pipeline includes individualized neoantigen therapies, off-the-shelf cancer antigen therapies, T-cell engagers, and cell therapy enhancers, with multiple programs in late-stage development and expansion into additional indications such as NSCLC and combinations with immunotherapies.

• Intismeran (mRNA-4157/V940) is being evaluated in multiple tumor types, with Phase 2 and 3 studies ongoing or completed in melanoma, NSCLC, RCC, and bladder cancer, and phase III data expected in 2026.

• Two off-the-shelf cancer antigen therapies, mRNA-4359 and mRNA-4106, are in clinical trials for advanced solid tumors, with mRNA-4359 advancing as a late-stage asset.

• T-cell engager mRNA-2808 is in Phase 1/2 for multiple myeloma, and cell therapy enhancer mRNA-4203 is entering clinical studies for solid tumors.

• The oncology pipeline has doubled in size over recent years, with ongoing studies in solid tumors and hematologic malignancies.

Key Clinical Data: Intismeran (mRNA-4157/V940)

• In Phase 2 adjuvant melanoma, mRNA-4157/V940 plus KEYTRUDA showed 74.8% recurrence-free survival at 3 years versus 55.6% for KEYTRUDA alone, reducing risk of recurrence or death by 49%.

• Distant metastasis-free survival improved, with a 62% reduction in risk of metastasis or death at 3 years.

• Safety profile was manageable and consistent with prior analyses, with no potentiation of immune-related adverse events.

• Phase 3 trial in adjuvant melanoma is fully enrolled, with data readout expected in 2026.

• INT is being evaluated across several cancer types, with phase III data expected in 2026, and has shown promising results in high-risk melanoma patients.

Key Clinical Data: mRNA-4359 (Off-the-Shelf Cancer Antigen Therapy)

• mRNA-4359 targets PD-L1 and IDO, aiming to enhance immune response and overcome tumor immune evasion, with a mechanism distinct from failed IDO inhibitors by using these as immune flags rather than enzymatic inhibition.

• In a phase I-II trial with 29 CPI-resistant melanoma patients, mRNA-4359 plus pembrolizumab showed a 24% overall response rate and over 50% disease control, with higher responses (67% ORR) in PD-L1 positive tumors and durable responses with median duration not reached.

• Safety profile was manageable, with no dose-limiting toxicities and immune-related adverse events consistent with single-agent pembrolizumab, mostly grade 1/2 AEs.

• mRNA-4359 elicited specific T-cell responses and novel clonal expansion, supporting the proposed mechanism and suggesting new immune education in responders.

• Phase 2 expansion includes arms in first-line and refractory melanoma and NSCLC, with endpoints including safety, ORR, DCR, and quality of life.