Monte Rosa Therapeutic (GLUE) Study Result summary

Interim phase I study results

• MRT-8102, a NEK7-directed molecular glue degrader, produced rapid, robust, and sustained reductions in hsCRP (up to 85%) and fibrinogen (31%) in both healthy volunteers and high CVD-risk subjects after four weeks of dosing, with 94% achieving hsCRP <2 mg/L.

• NEK7 degradation was rapid and sustained across all dose levels (5–400 mg), with 80-90% degradation observed even at the lowest dose tested.

• Significant reductions in IL-6 (up to 55%) and IL-1β (up to 80%) were observed, with evidence of CNS penetration and reduced CSF IL-6 in subjects with elevated baseline levels.

• MRT-8102 demonstrated potent inhibition of the NLRP3-IL-1β-IL-6-CRP axis, with no evidence of CRP rebound over four weeks.

• No serious or severe adverse events or increased infection risk were observed; adverse events were mild to moderate, self-resolving, and not dose-dependent.

Study design and population

• The phase I study included single and multiple ascending dose cohorts in healthy volunteers and a proof-of-concept or placebo-controlled cohort in high CVD-risk subjects, totaling up to 112 participants.

• SAD (48 subjects) and MAD (40 subjects) cohorts completed; CRP PoC (24 subjects) ongoing in high-risk CVD population with obesity and elevated CRP.

• Study endpoints included safety, tolerability, pharmacokinetics, NEK7 degradation, and changes in inflammatory biomarkers (hsCRP, IL-6, IL-1β, fibrinogen).

Study expansion and future plans

• The GFORCE-1 study will expand to additional dose levels and enroll approximately 108 subjects, aiming to accelerate development in ASCVD and inform future indications.

• Phase II ASCVD study (GFORCE-2) is planned for 2026, with data from the expanded GFORCE-1 expected in the second half of 2026.

• The program will also explore next-generation NEK7 degraders for broader indications, including MASH, recurrent pericarditis, gout, osteoarthritis, and asthma.