Moderna (MRNA) investor relations material

Oncology Portfolio Overview

• Advancing a diverse oncology portfolio using individualized and off-the-shelf mRNA therapies, targeting multiple cancer types and stages with various platform technologies.

• INT (mRNA-4157/V940) is a personalized mRNA therapy designed for each patient by sequencing tumor and healthy tissue to identify unique neoantigens, training the immune system to recognize and fight cancer.

• Three-year phase 2 data for INT plus Keytruda showed a 74.8% recurrence-free survival rate, reducing recurrence or death risk by 49% and distant metastasis risk by 62% compared to Keytruda alone, with a favorable safety profile.

• Phase 3 adjuvant melanoma study with INT and Keytruda completed enrollment in 2024, with data expected in 2026; additional pivotal and phase 2/3 studies are ongoing in melanoma, NSCLC, bladder, and renal cancers.

• Off-the-shelf cancer antigen therapies (mRNA-4359, mRNA-4106) target shared antigens, enabling broader and faster patient access, with ongoing phase 1/2 studies in multiple indications and combinations.

Platform Strategy and Innovation

• Portfolio strategy is to build a toolkit engaging the immune system differently depending on cancer stage, from prevention to advanced disease, with continued innovation in early detection, neo-adjuvant, adjuvant, and metastatic settings.

• T cell engagers (e.g., mRNA-2808) use multiplexing to target multiple antigens, including surface and intracellular targets, and can encode co-stimulatory signals, with phase 1/2 trials in relapsed refractory multiple myeloma.

• Cell therapy enhancers (e.g., mRNA-4203) are designed to boost the persistence and function of engineered T cells, with phase 1 studies in solid tumors and collaborations with Immatics.

• In vivo cell therapies use mRNA LNPs to engineer immune cells directly in the patient, aiming to overcome manufacturing and logistical hurdles of ex vivo therapies, with applications in CAR-M and CAR-T in preclinical development.

• Safety and strong CD8/CD4 T cell responses observed in individualized therapies are expected to translate across the portfolio, with translational endpoints guiding development.

Competitive Landscape and Partnerships

• Competitive differentiation includes proprietary algorithms, broader antigen coverage, and mRNA platform advantages over peptide-based or other mRNA competitors.

• Partnerships with Merck (INT, 50/50 cost and profit sharing) and Immatics (T cell receptor expertise) accelerate development and expand capabilities.

• Willingness to seek additional partnerships where external capabilities can accelerate or broaden development.

• Monitoring competitor data (e.g., BioNTech, IO Biotech) for read-through and de-risking, while recognizing platform and design differences.