– Preclinical Data Demonstrate Effects of MALT1 Inhibition on Suppression of Pro-inflammatory Cell Activation, Mitigation of Several Inflammatory Cytokines, and Efficacy in Disease Models –
– Studies Establish Dose-Related Relationships Between Efficacy and Treg Reduction, Establishing A Therapeutic Window for the Treatment of Autoimmune and Inflammatory Diseases –
– Findings Support Company’s Continued Advancement of MALT1 Inhibitor Drug in Clinical Trials for Autoimmune and Inflammatory Diseases –
CAMBRIDGE, Mass., May 9, 2022–(BUSINESS WIRE)–Rheos Medicines, a biopharmaceutical company providing molecular targeting and precision therapy for autoimmune and inflammatory diseases, today announced the publication of peer-reviewed preclinical data supporting the MALT1 inhibition as a new therapeutic strategy to treat autoimmune and inflammatory diseases. The new findings were published in Frontiers in immunology in a paper titled “Pharmacological inhibition of MALT1 enhances autoimmune pathogenesis and can be disentangled from effects on regulatory T cells.” Published data demonstrates that a MALT1 inhibitor drug can be designed to achieve efficacy by inhibiting the activity of multiple immune cell types to treat autoimmune and inflammatory diseases, while avoiding the reduction of beneficial regulatory T cells (Tregs).
“With the results of this publication, we have expanded the body of evidence demonstrating the promising potential of developing a MALT1 inhibitor for the treatment of a wide range of autoimmune and inflammatory diseases,” said Dania Rabah, Ph.D., scientific director. of Rheos and author of the publication. “The data indicate that we have successfully engineered a MALT1 inhibitor that interferes with systemic and tissue-specific drivers of disease and, importantly, exerts broad anti-inflammatory effects based on partial inhibition of the function effector in multiple immune cell types without reducing the number and benefit of regulatory T cells.These findings pave the way for new therapies that target MALT1.
“New targets for the treatment of autoimmune and inflammatory diseases have been slow to emerge, and there is a growing need for new treatment options for these diseases that affect millions of patients,” said John Davis, Jr. , MD, MPH, MS and Member of the Rheos Board of Directors. “While inhibition of MALT1 has held therapeutic promise for some time due to its anti-inflammatory effects, there has been some uncertainty about its actual effect on regulatory T cells. These impressive data demonstrate for the first time the potential to achieve efficacy without impacting regulatory T. These findings provide compelling evidence in the development of therapies that target the MALT1 pathway for many autoimmune and inflammatory diseases.
In the publication, Rheos scientists describe studies investigating the dose-dependent effects of MALT1 inhibition on several primary human cells, disease pathogenesis in a rat model of arthritis, and cell function. regulatory T (Tregs). These results indicate that a favorable therapeutic window is accessible and may extend beyond what has been observed in disease-free naïve animals. The document includes these key findings:
MALT1 inhibition attenuated the effector functions of several primary human cell types implicated in the pathogenesis of autoimmune and inflammatory diseases and blocked cytokine expression in stimulated whole blood from several species.
Pharmacological inhibition of MALT1 reduced disease severity and synovial cytokine production in a preclinical model of arthritis.
Efficacy can be decoupled from Treg reduction, with lower systemic concentrations of MALT1 inhibitor required to reduce disease severity compared to those required to reduce Treg counts.
The adverse MALT1 inhibitor-induced reduction in Treg was less pronounced in diseased rats than in naïve rats, showing the potential to expand the therapeutic window of a MALT1 inhibitor drug.
The published data supports Rheos Medicines’ development of its lead product candidate, RHX-317, a novel small molecule MALT1 inhibitor being developed for the treatment of several autoimmune diseases. Due to the role of MALT1 in cellular metabolism that differs between heterogeneous patient subgroups, the clinical activity of RHX-317 will be monitored by metabolite signatures in clinical studies, opening the possibility for Rheos to adopt a precision medicine approach to monitoring disease and therapeutic effect in the treatment of autoimmune diseases. RHX-317 has demonstrated efficacy in several validated disease models, including chronic graft versus host disease (cGVHD), rheumatoid arthritis and lupus nephritis.
MALT1 (mucosa-associated lymphoid fabric lymphoma translocation protein 1) is a dual-function scaffold molecule and a paracaspase that is preferentially expressed in immune cells. In addition to its role in NF-κB-mediated lymphocyte activation and proliferation, Rheos showed that MALT1 activity is central to the anabolic change that fuels pathogenic functions of immune cells. Inhibition of MALT1 simultaneously attenuates the activity of multiple immune cell types to dampen the inflammatory response in the activated immune system. Due to its role in cellular metabolism, the effects of MALT1 inhibition can be monitored by metabolite signatures, opening the possibility to monitor disease and assess the activity of therapeutics in patients and sub-groups. patient groups.
About Rheos drugs
Rheos Medicines is a biopharmaceutical company developing novel small molecule drugs to treat autoimmune and inflammatory diseases with greater precision by targeting the metabolic centers of the immune system. Using our proprietary MetPM™ platform, the Rheos team integrates an unparalleled knowledge base of immunometabolism networks based on bioinformatics integration of genetic, transcriptomic, epigenomic and metabolomic datasets, including from patient data and samples. We have built a pipeline of novel differentiated drug programs to treat autoimmune and inflammatory diseases by targeting the fundamental underpinnings of immune system dysfunction while identifying molecular signatures for patient stratification and selection. Rheos has brought together leading scientists whose discoveries have opened up the field of immunometabolism, clinicians with a deep understanding of immune-mediated diseases, and a management team experienced in biotechnology. Rheos was founded by Third Rock Ventures and is located in Cambridge, MA. For more information, please visit www.rheosrx.com/. We invite you to follow us on LinkedIn and @Rheosrx.
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Kathryn Morris, The Yates Network LLC
Hannah Deresiewicz, Stern Investor Relations, Inc.