MRT-8102

DEVELOPMENT STEP phase-1

SPONSOR MATRIX Monte Rosa Therapeutics [GLUE]

MECHANISM TARGET // UNMAPPED_TARGET

[THERAPEUTIC_PROFILE]

Target Indications

IL-1β/NLRP3 driven Inflammatory Diseases

Mechanism Abstract

NEK7 and aberrant NLRP3 inflammasome activation has been implicated in multiple inflammatory disorders, including cardiovascular disease, gout, osteoarthritis, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, and metabolic disorders. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β and interleukin-18 (IL-18) release both in vitro and in vivo. MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NLRP3 inflammasome. In a non-human primate model, MRT-8102 potently, selectively, and durably degrades NEK7 and results in near-complete reductions of IL-1β following ex vivo stimulation of whole blood. MRT-8102 has shown a favorable profile in GLP toxicology studies.

[3D_INTERACTIVE_CONFORMATION]

PUBCHEM CID: 176157253

INTERACTIVE_3D_CONFORMATION

     INITIALIZING_STRUCTURAL_BIOMATRIX... 

[CLINICAL_TRIALS_REGISTRY]

TOTAL EXTRACTED1

RECRUITING STATUS0

COMPLETED RUNS0

REGISTRY & PHASE

TESTED CONDITION

STUDY TITLE & LIFECYCLE TIMELINES

STATUS

➔

P-1NCT07119125

Healthy VolunteersElevated CRP

N=100Est. Finish: 2026-07

A First-in-human, 3-part Study of MRT-8102 in Healthy Participants and Participants at Cardiovascular Risk With Elevated CRP

active not recruiting

ENROLLMENT PATIENT CAPACITY100 Patients(estimated)

ESTIMATED RUN COMPLETION MILESTONES

Start Date:2025-06-27(actual)

Primary End:2026-07(estimated)

Study Finish:2026-07(estimated)

OFFICIAL PROTOCOL TITLE

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single and Multiple Dose Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MRT-8102 in Healthy Participants and in Participants at Cardiovascular Risk With Elevated CRP

[INVESTIGATORS_&_FACILITY_ROSTER]

// NO_EXPLICIT_INVESTIGATORS_OR_ROSTERS_LOGGED

[PRIMARY_SUCCESS_ENDPOINTS]

To evaluate the safety and tolerability of single doses of MRT-8102 in healthy adult participants

Analysis Window: 15 days

To evaluate the safety and tolerability of multiple ascending doses of MRT-8102 in healthy adult participants.

Analysis Window: 21 days

To evaluate the safety and tolerability of 28-day daily dosing of MRT-8102 in participants at cardiovascular risk with elevated CRP

Analysis Window: 56 days

[SECONDARY_SUCCESS_ENDPOINTS]

Characterize the PK Profile (peak plasma concentration) of MRT-8102 after single doses of MRT-8102 in healthy adult participants

Analysis Window: Up to 8 days

Characterize the PK Profile (plasma concentration versus time) of MRT-8102 after single doses of MRT-8102 in healthy adult participants

Analysis Window: Up to 8 days

Assess the effect of a high-fat/high-calorie meal on the PK (peak plasma concentration) of MRT-8102 02 in healthy adult participants

Analysis Window: Up to 8 days

Assess the effect of a high-fat/high-calorie meal on the PK (plasma concentration versus time) of MRT-8102 02 in healthy adult participants

Analysis Window: Up to 8 days

Characterize the PK profile (peak plasma concentration) of MRT-8102 in plasma after multiple doses of MRT-8102 in healthy adult participants

Analysis Window: Up to 14 days

Characterize the PK profile (plasma concentration versus time) of MRT-8102 in plasma after multiple doses of MRT-8102 in healthy adult participants

Analysis Window: Up to 14 days

Characterize the PK Profile (peak plasma concentration) of MRT-8102 when administered daily to participants at cardiovascular risk with elevated CRP

Analysis Window: Up to 35 days

Characterize the PK Profile (plasma concentration versus time) of MRT-8102 when administered daily to participants at cardiovascular risk with elevated CRP

Analysis Window: Up to 35 days

[COHORT_ARMS_ARCHITECTURE_BREAKDOWN]

Part 1: Single Ascending Dose (MRT-8102)

EXPERIMENTAL

Single Dose of MRT-8102

Part 1: Single Ascending Dose (Placebo)

PLACEBO_COMPARATOR

Single Dose of Placebo

Part 2: Multiple Ascending Dose (MRT-8102)

EXPERIMENTAL

7-day Daily Dose of MRT-8102

Part 2: Multiple Ascending Dose (Placebo)

PLACEBO_COMPARATOR

7-day Daily Dose of Placebo

Part 3: elevated CRP (MRT-8102)

EXPERIMENTAL

28-day Daily Dose of MRT-8102

Part 3: elevated CRP (Placebo)

PLACEBO_COMPARATOR

28-day Daily Dose of Placebo

[DOSING_&_INTERVENTION_SPECIFICITIES]

MRT-8102DRUG

Oral capsules

PlaceboDRUG

Oral capsules

[BIOCHEMICAL_STRUCTURE_REGISTRY]

MOLECULAR FORMULAC21H22Cl2N4O3

MOLECULAR WEIGHT449.3 g/mol

PARTITION (XLogP)2.6

H-BOND DONORS2

H-BOND ACCEPTORS5

COMPLEXITY SCORE655

SMILES (CANONICAL / ISOMERIC)

CC1=CN=C(N=C1)C(C)(C)C(=O)NCC2=CC(=C(C(=C2)Cl)C3CCC(=O)NC3=O)Cl

INCHI KEYVKROEWYACWPSOG-UHFFFAOYSA-N

3D_CONFORMER_VIEWPORT

View Registry Record in PubChem [CID: 176157253] →