GLUE: ZEUS Rising: Potential Read Through to MRT-8102

Research evidence excerpt

GLUE: ZEUS Rising: Potential Read Through to MRT-8102

Biotechnology Equity Research

Exhibit 2 - Relevant Anti-inflammatory Mechanism CVOT Comps

Source: Novo Nordisk slides; N Engl J Med 2017;377:1119-1131; N Engl J Med

2019;381:2497-2505; N Engl J Med 2020;383:1838-1847; JACC Volume 71, Number 21; Wells

Fargo Securities, LLC

CANTOS efficacy taken from 150mg dose (n=2,284) and post-hoc analyses are taken across dose

levels; 1- Samples were taken from 9,534 participants with atleast 3 months of treatment, n=3,182

pbo vs. n=2,868 hsCRP >2mg/L; 2- Subgroup includes n= 1,249 treatment vs. n=626 pbo; 3-

Nonfatal MI, any nonfatal stroke, or CV death; 4-CV death, resuscitated cardiac arrest, MI, stroke,

or urgent hospitalization for angina leading to coronary revascularization; 5- CV death, MI, ischemic

stroke or ischemia-driven coronary revascularization; 6= hsCRP levels after 3 month's of treatment

How strong is the IL-6 read through to NLRP3/NEK7? While a positive ZEUS outcome

would not directly validate NLRP3/NEK7 inhibition, positive outcomes from both

CANTOS (IL-1β) and ZEUS (IL-6) could provide compelling clinical validation of the broader

inflammasome pathway. Importantly, because NLRP3/NEK7 sit upstream of IL-1β and

IL-6 one could argue a successful strategy at the IL-6 levels leaves room for greater

efficacy upstream, balancing differing patient baseline and enrichment factors.

Implications for MRT-8102. Prior data (see our note here) demonstrate MRT-8102's

ability to meaningfully reduce hsCRP and IL-1β in patients with elevated hsCRP, with

hsCRP reductions generally in-line with zilti. Importantly, GLUE has designed MRT-8102's

CV program around a similar elevated hsCRP population being studied in ZEUS, with