Monte Rosa Therapeutic (GLUE) investor relations material

Pipeline overview and strategic focus

• Focused on developing molecular glue degraders targeting undruggable or hard-to-drug proteins, spanning oncology, inflammation, and immunity.

• Oncology pipeline led by GSPT1 degrader MRT-2359, advancing to phase II in AR mutant castration-resistant prostate cancer after promising early data.

• Cyclin E1 molecular glue degrader IND submission expected in the second half of the year as part of the cyclin E1/CDK2 program.

• Inflammation pipeline includes VAV1 degrader MRT-6160 (licensed to Novartis, multiple phase II trials planned) and NEK7 degrader MRT-8102, with proof-of-concept data already shared.

• Additional undisclosed targets under evaluation, including through partnerships with Roche and Novartis.

Oncology program updates

• MRT-2359 showed strong PSA responses in AR mutant metastatic castration-resistant prostate cancer, with all five evaluable patients responding and two achieving PSA 90.

• Phase II study for MRT-2359 will enroll up to 25 AR mutant patients using a two-stage design, with interim analysis to determine continuation.

• Enrollment expected to proceed quickly at specialized prostate cancer centers, with study initiation guided for Q3.

• Future development may expand beyond AR mutant prostate cancer, exploring earlier disease settings and combination therapies.

• Cyclin E1 degrader positioned for single-agent use in cyclin E1-amplified ovarian cancer, while CDK2 degrader is aimed at combination therapy in breast cancer.

Differentiation and safety considerations

• Molecular glue degraders offer improved selectivity and reduced off-target toxicity compared to traditional inhibitors.

• Cyclin E1 and CDK2 degraders bind via protein-protein interactions, avoiding ATP pocket-related selectivity issues.

• Early clinical experience suggests a broad pharmacodynamic index, enabling target degradation at multiple dose levels.

• For cyclin E1-amplified ovarian cancer, response rates above 30–35% and durability over 6 months would be meaningful.