Monte Rosa Therapeutic (GLUE) Jefferies London Healthcare Conference 2024 summary

Platform strategy and technology

• Chose molecular glue degraders for broader target access, as they do not require a binding pocket on the target protein, unlike PROTACs.

• Platform enables targeting proteins previously inaccessible to other degradation technologies.

• Focused on a handful of reprogrammable E3 ubiquitin ligases, with Cereblon as the primary one currently used.

• Five years of progress have expanded understanding and application of the platform.

Oncology pipeline and clinical progress

• GSPT1 program (MRT-2359) targets MYC-driven tumors, especially lung cancers, with 60-70% degradation optimized for efficacy and safety.

• Phase 1 data showed partial responses and stable disease at low doses, with no clear dose response due to early achievement of target degradation.

• Modified dosing schedule (21/7) aims for more consistent exposure and easier management of missed doses.

• Phase 2 expansions use a two-stage design with predefined efficacy bars, though specific thresholds are undisclosed.

• Next data update expected by year-end, with a larger, biomarker-positive patient cohort.

Immunology and partnership developments

• Announced a major partnership with Novartis for the VAV1 program, including $150M upfront, up to $1.5B in milestones, and a 30% US profit share.

• VAV1 targets both T and B cell signaling, with a focus on Th17 cells and B cell receptor pathways, offering a combinatorial mechanism.

• Ulcerative colitis and rheumatoid arthritis remain high-priority indications, pending joint development committee decisions.