MRT-6160 / Monte Rosa Therap, Novartis - LARVOL DELTA

Monte Rosa Therapeutics to Present Pipeline Update and Release Fourth Quarter and Full Year 2024 Financial Results on March 20, 2025 (GlobeNewswire) - "Monte Rosa Therapeutics, Inc...announced that management will present a pipeline update including clinical results from its Phase 1 SAD/MAD study of the VAV1-directed MGD MRT-6160 and its Phase 1/2 study of MRT-2359 in MYC-driven solid tumors. A conference call and webcast are planned for Thursday, March 20, 2025, at 8:00 a.m. ET."

P1 data • P1/2 data • HER2 Negative Breast Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Prostate Cancer • Small Cell Lung Cancer

Monte Rosa Therapeutics Provides Corporate Update and Key Anticipated Milestones for 2025 (GlobeNewswire) - "Key Anticipated Milestones for 2025: Share updated data, including biomarker and activity data, from the MRT-2359 Phase 1/2 study in Q1 2025. Report initial data from the Phase 1 SAD/MAD study of MRT-6160 in healthy volunteers in Q1 2025, including data on safety, pharmacokinetics, VAV1 protein degradation, and key downstream pharmacodynamic markers....Nominate a development candidate for the second-generation NEK7 program with enhanced CNS penetration in H2 2025. Nominate a CDK2 program development candidate in H1 2025."

New molecule • P1 data • P1/2 data • Diffuse Large B Cell Lymphoma • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Prostate Cancer • Small Cell Lung Cancer

Monte Rosa Therapeutics Announces Closing of Global License Agreement with Novartis to Advance T and B Cell-modulating VAV1-directed Molecular Glue Degraders (GlobeNewswire) - "Monte Rosa Therapeutics, Inc...announced the closing of the Company’s previously announced global exclusive development and commercialization license agreement with Novartis to advance VAV1-directed MGDs, including MRT-6160. Under the terms of the agreement, Novartis will obtain exclusive worldwide rights to develop, manufacture, and commercialize MRT-6160 and other VAV1 MGDs and will be responsible for all clinical development and commercialization, starting with Phase 2 clinical studies. Monte Rosa remains responsible for completing the ongoing Phase 1 clinical study of MRT-6160. Novartis has agreed to pay Monte Rosa $150 million up front. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies, as well as tiered royalties on ex-U.S. net sales."

Licensing / partnership • Oncology

First-in-human Study of MRT-6160 in Healthy Subjects (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: Monte Rosa Therapeutics, Inc

New P1 trial

Monte Rosa Therapeutics Announces First Participants Dosed in MRT-6160 Phase 1 Study (GlobeNewswire) - "Monte Rosa Therapeutics, Inc...announced that the first participants have been dosed in a Phase 1, single ascending dose / multiple ascending dose (SAD/MAD), healthy volunteer study evaluating MRT-6160, a VAV1-directed MGD being developed for systemic and neurological autoimmune diseases. The Company expects to obtain initial data from the Phase 1 study in Q1 2025."

P1 data • Trial status • Immunology • Inflammatory Bowel Disease • Rheumatoid Arthritis • Ulcerative Colitis

Monte Rosa Therapeutics Provides Development Progress Updates on MRT-2359 and MRT-6160 (GlobeNewswire) - "'Moreover, today we are excited to announce the submission of our Investigational New Drug (IND) application to the U.S Food and Drug Administration (FDA) for MRT-6160, a highly selective and orally bioavailable MGD directed against VAV1.'...MRT-6160 is on track for initiation of a Phase 1 SAD/MAD study this summer with Phase 1 clinical data expected in Q1 2025. Monte Rosa expects to subsequently initiate proof-of-concept (POC) studies in autoimmune/inflammatory diseases including ulcerative colitis and rheumatoid arthritis, with additional potential POC studies in dermatology, rheumatology, and neurology indications."

IND • Dermatology • Immunology • Rheumatoid Arthritis • Rheumatology • Ulcerative Colitis

MRT-6160, A VAV1-DIRECTED MOLECULAR GLUE DEGRADER, REDUCES JOINT INFLAMMATION, CYTOKINE PRODUCTION, AND AUTOANTIBODY LEVELS IN A COLLAGEN-INDUCED ARTHRITIS DISEASE MODEL (EULAR 2024) - "MRT-6160 is a highly selective and orally bioavailable molecular glue degrader targeting VAV1, a key signaling protein in lymphocytes. MRT-6160-mediated degradation of VAV1 attenuates TCR- and BCR-mediated activation in vitro and inhibits disease progression and autoimmune proinflammatory effector functions in vivo warranting clinical investigation."

Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Targeted Protein Degradation • CD69 • IL17A • IL1B • IL6 • VAV1

MRT-6160, A VAV1-DIRECTED MOLECULAR GLUE DEGRADER, INHIBITS DISEASE PROGRESSION IN A T-CELL TRANSFER MEDIATED MURINE COLITIS MODEL CONCOMITANT WITH REDUCED CALPROTECTIN EXPRESSION (DDW 2024) - "MRT-6160-mediated degradation of VAV1 a previously undruggable target inhibits T-cell transfer-induced colitis concomitant with reduced calprotectin subunit expression demonstrating activity in this preclinical model. These data suggest that VAV1 degradation could have therapeutic benefit in IBD patients and warrants clinical assessment."

IO biomarker • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Targeted Protein Degradation • VAV1

Monte Rosa Therapeutics Presents Preclinical Data at Digestive Disease Week 2024 Highlighting Therapeutic Potential of MRT-6160 in Inflammatory Bowel Disease (GlobeNewswire) - "Monte Rosa Therapeutics, Inc...announced the company will present preclinical data at Digestive Disease Week (DDW) 2024, being held May 18-21 in Washington, D.C. The data showed that MRT-6160-mediated degradation of VAV1 inhibited disease progression in a T-cell transfer murine model of colitis. VAV1 is a key signaling protein downstream of both the T-and B-cell receptors and its degradation has potential to treat multiple T-cell and/or Th17 mediated autoimmune and inflammatory diseases, including ulcerative colitis (UC)....'MRT-6160 is on track for an IND submission this quarter with initiation of a Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study mid-year. We look forward to sharing clinical data from this program in Q1 2025.'"

IND • New P1 trial • P1 data • Preclinical • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

MRT-6160, a VAV1-directed molecular glue degrader, inhibits disease progression and inflammation in a T-cell transfer model of Colitis. (ECCO-IBD 2024) - "Conclusion MRT-6160 demonstrates strong activity in a preclinical model of colitis reducing DAI, effector cytokine production, and colon tissue damage. These data suggest that MRT-6160-mediated degradation of VAV1 may have therapeutic benefit in IBD patients and warrants further clinical development."

IO biomarker • Immunology • Inflammation • Inflammatory Bowel Disease • IL17A • IL6 • VAV1

A VAV1-Directed Molecular Glue Degrader, MRT-6160, Reduces Joint Inflammation in a Collagen-Induced Arthritis Autoimmune Disease Model (ACR Convergence 2023) - "In positive control groups, mice were administered either 1 mg/kg dexamethasone (daily via intraperitoneal injection) or 500 µg anti-TNF (three times weekly via intraperitoneal injection). The VAV1-targeting MGD MRT-6160 attenuates disease progression in the autoimmune CIA model with a therapeutic treatment regimen. This warrants further investigation of MRT-6160 in a clinical setting. A."

Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Targeted Protein Degradation • CRBN • VAV1

Monte Rosa Therapeutics Announces Third Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "The Company now expects to release the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study in Q2 2024. On track for planned IND submission for MRT-6160 in the first half of 2024. The Company expects to nominate a development candidate for its NEK7 preclinical program in Q1 2024. The Company expects to nominate a development candidate for its CDK2 preclinical program in 2024."

IND • P1/2 data • Pipeline update • Immunology • Oncology • Solid Tumor

Monte Rosa Therapeutics Presents Preclinical Data at ACR Convergence 2023 Demonstrating Potential of MRT-6160, a VAV1-targeted Molecular Glue Degrader, to Treat Immunological and Inflammatory Diseases (GlobeNewswire) - "Data presented support broad potential therapeutic applications of MRT-6160 in a variety of autoimmune and inflammatory disorders driven by underlying dysregulation of T- and B-cells, including rheumatoid arthritis...In vitro, MRT-6160 induced selective degradation of VAV1, and attenuated TCR- and BCR-mediated activation and function of primary human T- and B-cells. In the CIA model, oral dosing of MRT-6160 elicited rapid VAV1 degradation across multiple tissues in a dose-dependent manner. Over the course of 20 days, MRT-6160 significantly decreased disease progression and endpoint functional scores compared to vehicle and showed a trend towards superior activity compared to an anti-TNF antibody."

Preclinical • Immunology • Rheumatoid Arthritis

Monte Rosa Therapeutics Announces $25 Million Registered Direct Offering, Priced At- the-Market Under Nasdaq Rules (Monte Rosa Therap Press Release) - "Monte Rosa Therapeutics, Inc...today announced that it has raised $25 million at-the-market from a life sciences-dedicated investor....Monte Rosa intends to use the net proceeds from the offering towards its further advancement of its clinical and late preclinical pipeline, including MRT-2359, its orally bioavailable, GSPT1-directed MGD, MRT-6160, its orally bioavailable VAV1-directed MGD, and its NEK7 program, to key value inflection points."

Financing • Immunology • Oncology

Monte Rosa Therapeutics Advances Second Development Candidate, MRT-6160, a Novel, Highly Selective Molecular Glue Degrader Targeting VAV1 for the Treatment of Autoimmune Diseases (GlobeNewswire) - "Monte Rosa Therapeutics, Inc...announced its second development candidate, MRT-6160, a novel, potent, and selective molecular glue degrader (MGD) of VAV1. The Company plans to file an Investigational New Drug (IND) application for MRT-6160 in the first half of 2024 and to develop the molecule as a potential treatment for autoimmune diseases."

IND • Pipeline update • Immunology

Monte Rosa Therapeutics Announces First Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "On track to announce initial clinical data, including pharmacokinetic (PK), pharmacodynamic (PD), safety, and available initial efficacy data from the Phase 1 part of the ongoing Phase 1/2 clinical trial evaluating MRT-2359 in MYC-driven tumors, including non-small cell lung cancer, small cell lung cancer, and other MYC-driven tumors, in the second half of 2023; On track to advance multiple preclinical programs to development candidates in immunology, inflammation, and oncology, including declaring a VAV1 development candidate in the second quarter of 2023..."

P1 data • Pipeline update • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lung Cancer • Lymphoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer