Monte Rosa Therapeutics Begins MRT-6160 Phase 1 Dosing

Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE) has announced the commencement of the first dosing of participants in a Phase 1 clinical trial of MRT-6160, a novel molecular glue degrader (MGD) targeting VAV1. This clinical-stage biotechnology company is focusing on the development of MGD-based medicines, specifically for systemic and neurological autoimmune and inflammatory diseases. Initial findings from this trial are expected in the first quarter of 2025.

MRT-6160 is a highly selective and potent VAV1-directed MGD designed to degrade proteins that have previously been difficult to target with traditional therapies. By focusing on VAV1, a crucial regulator of T- and B-cell receptor activity, this therapeutic approach aims to offer a novel method for treating various autoimmune and inflammatory conditions. Monte Rosa Therapeutics believes this to be a pioneering step, as MRT-6160 is touted as the first rationally designed MGD for a non-oncology indication.

Dr. Markus Warmuth, CEO of Monte Rosa Therapeutics, expressed enthusiasm about the initiation of the Phase 1 study. He emphasized that their MGD-based therapeutic approach is tailored to degrade challenging proteins, presenting opportunities to target previously undruggable proteins like VAV1. The Phase 1 clinical trial is structured to provide preliminary data on the safety, pharmacokinetics, and pharmacodynamic effects of MRT-6160. This includes monitoring the degradation of VAV1 protein and downstream markers such as CD69, IL-2, IL-6, and IL-17. The insights obtained will guide the clinical strategy further. Following the initial clinical data, the company plans to commence proof-of-concept studies in ulcerative colitis, rheumatoid arthritis, and potentially other conditions.

Preclinical studies have provided support for the development of MRT-6160, validating its potential in treating systemic and neurologic autoimmune conditions. The investigational drug has demonstrated potent and selective degradation of VAV1 in vitro in human T and B cells and has shown promising results in preclinical models of autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis.

MRT-6160 is characterized by its high potency, selectivity, and oral bioavailability. Preclinical studies have highlighted its capability to deeply degrade VAV1 without impacting other proteins. VAV1, part of the Rho-family guanine nucleotide exchange factors, is a critical signaling protein downstream of T- and B-cell receptors. It is primarily expressed in blood and immune cells, including T and B cells. Targeted degradation of VAV1 through an MGD impacts both T- and B-cell receptor-mediated activities, reducing cytokine secretion essential for sustaining autoimmune diseases. The effectiveness of VAV1-directed MGDs has been demonstrated in various preclinical models, indicating potential therapeutic benefits in numerous systemic and neurological autoimmune diseases, including inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and dermatological disorders. MRT-6160 has shown significant potential in inhibiting disease progression in several in vivo autoimmunity models.

Monte Rosa Therapeutics is dedicated to developing highly selective MGD medicines targeting serious diseases, particularly in oncology, autoimmune, and inflammatory diseases. MGDs are small molecules capable of degrading specific proteins, offering treatment potential for conditions that have been challenging for other modalities. The company’s QuEEN™ discovery engine leverages AI-guided chemistry and diverse chemical libraries to identify degradable protein targets and design MGDs with exceptional selectivity. Monte Rosa Therapeutics has established a leading pipeline of MGDs across various therapeutic areas and maintains a strategic partnership with Roche to discover and develop MGDs for cancer and neurological diseases previously considered undruggable.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!