Candidate therapy MRT-6160 chosen for MS, other autoimmune diseases
Early studies are underway that would support therapy's IND application
Monte Rosa Therapeutics has selected MRT-6160, its second candidate for development, for treating multiple sclerosis (MS) and several other autoimmune diseases.
The therapy is now in early studies that would support an investigational new drug (IND) application, a formal request to U.S. regulatory authorities to start testing a new therapy in humans. The company plans to submit the application in the first half of 2024.
“Our goal centers on pioneering therapeutically meaningful new drugs for patients with serious diseases,” Markus Warmuth, MD, CEO of Monte Rosa, said in a company press release. “We anticipate significant progress and milestones in our portfolio in the upcoming year, including … filing of an IND application for MRT-6160 in the first half of next year.”
In autoimmune diseases, the immune system mistakenly mounts an attack against the body’s own molecules, damaging cells and tissues. Such responses are mediated by two immune cell types — B-cells and T-cells — which produce antibodies and release pro-inflammatory molecules that spread the inflammation.
Monte Rosa’s focus is on identifying therapeutically relevant protein targets that may be susceptible to degradation by the action of molecular glue degraders (MGD). After selecting the best targets by means of artificial intelligence, the company uses its QuEEN proprietary platform to design potent MGDs that are selective against such targets.
Targeting VAV1, a new approach
MRT-6160 is a small molecule MGD that uses cell mechanisms to eliminate the VAV1 protein, which is needed for immune B- and T-cells to function properly.
“MRT-6160 is expected to be our second MGD to enter clinical trials, showcasing the continued productivity of our QuEEN platform,” Warmuth said.
Preclinical studies showed targeting VAV1 for degradation via an MGD reduced the activity of these cells, as measured by a significant decrease in the proteins involved in inflammation.
MGDs targeting VAV1 have also been able to slow disease progression in animal models of autoimmune conditions, suggesting they might have therapeutic benefits in several of those disorders, including MS, rheumatoid arthritis, and skin conditions.
“Our in vitro studies have shown that MRT-6160 selectively degrades VAV1 without detectable effects on other proteins. By targeting VAV1, MRT-6160 attenuates multiple aspects of T- and B-cell function and inhibits disease progression in established [animal] models of autoimmunity,” said Owen Wallace, PhD, chief scientific officer of Monte Rosa. “The underlying biology and our preclinical data both demonstrate that MRT-6160 acts as an immune modulator, which has the potential to avoid the broad immune suppression seen with other approaches.”
Warmuth called MRT-6160 a “potentially groundbreaking therapy” for T-cell and B-cell mediated autoimmunity by focusing on VAV1, which he called a “validated but previously undruggable target.”
“We look forward to progressing our clinical plan developed with the goal of providing early insights into safety, [pharmacological properties], and proof of concept regarding differentiated effects on key immunomodulatory signaling pathways,” Wallace said.
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