Pipeline

MRT-6160 (DDY391) is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in our in vitro studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple systemic and neurological autoimmune indications, such as Sjogren’s disease, psoriatic arthritis, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and dermatological disorders. Preclinical studies demonstrate MRT-6160 inhibits disease progression in in vivo autoimmunity models. Details about the ongoing study, “A Phase 2a/b Study to Assess the Efficacy, Safety and Tolerability of DDY391 in Participants With Sjogren’s Disease,” can be found at ClinicalTrials.gov under identifier: NCT07737743. Details about the ongoing Phase 2a/b study, “A Study to Assess the Efficacy, Safety and Tolerability of DDY391 in Participants With Moderate to Severe Psoriatic Arthritis,” can be found at ClinicalTrials.gov under identifier: NCT07801495.

In October 2024 we entered into a global exclusive development and commercialization license agreement with Novartis to advance VAV1 MGDs including MRT-6160. Under the terms of the agreement, Monte Rosa received a $150 million upfront payment. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies. Monte Rosa will co-fund any Phase 3 clinical development and will share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the U.S., and is also eligible for tiered royalties on ex-U.S. net sales.

MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases linked to NLRP3 and IL-1 dysregulation. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation, and IL-1β release both in vitro and in vivo. NLRP3 inflammasome activation causes pyroptotic cell death, leading to the release of highly inflammatory cytokines including IL-1α/β and IL-18, and DAMPs such as HMGB1, calprotectin, and calgranulin C. DAMPs further stimulate NLRP3 activity while promoting NLRP3-independent cytokine and chemokine production in neighboring cells. Together, DAMPs and IL-1 are responsible for the majority of the local inflammation and tissue changes characteristic of ASCVD, gout, hidradenitis suppurativa, and other indications. The NEK7/NLRP3 inflammasome plays a multifaceted role in plaque biology, contributing to plaque formation, plaque growth, vessel wall alterations, and thrombosis.

Monte Rosa recently completed the GFORCE-1 study of MRT-8102 in subjects with elevated cardiovascular disease risk. Details about the study can be found at ClinicalTrials.gov under identifier: NCT07119125. Monte Rosa expects to initiate Phase 2 studies of MRT-8102 in patients with coronary artery disease, gout flares, and hidradenitis suppurativa.

MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) of GSPT1. MYC-driven cancers, including prostate cancer, depend on enhanced translation of oncoproteins to support rapid growth. MRT-2359 exploits this therapeutic vulnerability by disrupting translation through selective degradation of the translation termination factor GSPT1. MRT-2359 treatment reduced cellular abundance of many prostate cancer-relevant oncoproteins, including androgen receptor (AR), MYC, and Cyclin D1-E2F, and demonstrated robust anti-tumor activity across multiple preclinical models of metastatic castration-resistant prostate cancer (mCRPC). In heavily pretreated mCRPC patients, MRT-2359 in combination with the AR inhibitor enzalutamide has demonstrated encouraging early signals of clinical response. Details about our ongoing Phase 2 study,  “MODeFIRe-1 (Molecular Degrader for Inhibitor Resistance): A Phase 2, Open-Label, Multicenter Study of Oral MRT-2359 in Combination with Apalutamide in Patients With Castration-Resistant Prostate Cancer” can be found at ClinicalTrials.gov under identifier: NCT07745361.

Cyclin proteins play crucial roles in regulating cell cycle progression by binding and activating cyclin-dependent kinases (CDK). Cyclin E1 (CCNE1) is a principal oncogenic driver, amplified in multiple cancers, including ovarian, endometrial, gastric and breast, and its expression in tumor cells is associated with poor prognosis. In these areas of significant unmet medical need, selective elimination of cyclin E1 is expected to provide vital benefit to patients with aggressive malignancies. Once considered an “undruggable” cancer target by conventional small molecule inhibitor approaches, we have identified multiple MGD molecules that selectively degrade cyclin E1.

Cyclin-dependent kinase 2 (CDK2) is a key driver of cell cycle progression in cancer, acting in coordination with CDK4 and CDK6 to drive cell proliferation. CDK4/6 inhibitors are FDA-approved agents for the treatment of HR-positive/HER2-negative breast cancer; however, many patients become resistant because their tumors become reliant on CDK2. Targeting CDK2 in conjunction with CDK4/6 inhibition has the potential to provide more sustained clinical responses. In preclinical studies, Monte Rosa’s CDK2-targeted MGDs have demonstrated highly selective degradation of CDK2, with no detectable off-target activity.

In October 2023, Monte Rosa entered into a strategic collaboration and licensing agreement with Roche to discover and develop MGDs against targets in cancer and neurological diseases.

In September 2025, Monte Rosa entered into an agreement to collaborate with Novartis to develop novel degraders for immune-mediated diseases.