Monte Rosa Therapeutic (GLUE) UBS Targeted Protein Degradation Day 2024 summary

Platform and scientific approach

• Focuses on molecular glue degraders to target undruggable proteins, leveraging in-house machine learning and AI to analyze protein-protein interactions and optimize degrader design.

• Platform integrates experimental screening and mass spectrometry data to refine AI models, creating a unique feedback loop.

• Initial emphasis on Cereblon as the E3 ligase due to its high PPI propensity and available data, with expansion to other ligases underway.

• AI-driven analysis of over 600 ligases to identify new targets with suitable PPI surfaces and binding pockets.

Pipeline overview and development timelines

• MRT-2359, a molecular glue degrader targeting GSPT1, is in Phase 1 for oncology, focusing on tumors driven by c-Myc and L-Myc.

• MRT-6160 targets VAV1 for autoimmune diseases, with IND filed and healthy volunteer trials planned; NEK7 program targets NLRP3 inflammasome with IND expected in Q1 next year.

• CDK2 and Cyclin E degraders are in preclinical development for oncology indications such as breast and ovarian cancer.

• No pivot between oncology and I&I; target selection is based on unmet need and unique platform capabilities.

Clinical and preclinical data highlights

• MRT-2359 Phase 1 dose escalation showed optimal PD modulation and safety at two dose levels; denser dosing regimens are being explored with updates expected in the second half of the year.

• Patient enrollment focuses on lung cancer and neuroendocrine tumors with high c-Myc/L-Myc expression; ongoing biomarker analysis guides further development.

• VAV1 preclinical data show efficacy in autoimmune models (IBD, RA, MS); healthy volunteer trial will assess degradation and biomarker changes, aiming for 80-90% degradation for efficacy.