The Science

MEK 1 and MEK 2 are kinases in the MAPK pathway, which drives cell proliferation, differentiation, and survival.

When this pathway is abnormally overactive, it can fuel tumors, fibrosis, and other diseases. MEK inhibitors work by blocking ERK activation, which can trigger cell death and slow tumor growth.

Current FDA-approved MEK inhibitors for NF1-PN have certain limitations: known toxicities and high rates of adverse events that can lead to dose interruptions, discontinuations, and/or poor tolerability.

PAS-004 is designed to address these issues through its macrocyclic structure, which we believe offers several advantages:

• Improved selectivity and higher oral bioavailability
• Better metabolic stability — structural rigidity enables stronger target binding
• No primary alcohol or hydroxamate group, a known metabolic liability in earlier MEK inhibitors, while still preserving key protein/ligand contacts

This translates into a favorable pharmacokinetic profile: a long half-life, a low peak-to-trough (Cmax/Cmin) ratio, and stable steady-state drug levels. We believe sustained MAPK suppression could mean better efficacy, safety, and a broader therapeutic window than current FDA-approved MEK inhibitors for NF1-PN.