– Preclinical data demonstrate effects of MALT1 inhibition on suppression of pro-inflammatory cell activation, attenuation of multiple inflammatory cytokines, and efficacy in disease models –
– Studies establish dose-dependent relationships between efficacy and Treg reduction, establishing a therapeutic window for treatment of autoimmune and inflammatory diseases –
– Results support the company’s continued advancement of a MALT1 inhibitor drug into clinical trials for autoimmune and inflammatory diseases –
CAMBRIDGE, Mass., May 9, 2022 – Rheos Medicines, a biopharmaceutical company bringing molecular targeting and precision treatment to autoimmune and inflammatory diseases, today announced the peer-reviewed publication of preclinical data supporting MALT1 inhibition as a novel 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 Ameliorates Autoimmune Pathogenesis and Can Be Uncoupled from Effects on Regulatory T cells.” The published data demonstrate 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 disease, while avoiding the reduction in beneficial regulatory T cells (Tregs).
“With the results in 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., Chief Scientific Officer of Rheos and an author of the publication. “The data indicate that we have succeeded in designing a MALT1 inhibitor that interferes with systemic and tissue-specific drivers of disease and, importantly, that it exerts broad anti-inflammatory effects based on partial inhibition of effector function in multiple immune cell types without reducing the number and benefit of regulatory T cells. These findings open a path toward new therapies that target MALT1.”
“Novel 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 which affect millions of patients,” said John Davis, Jr., M.D., M.P.H., M.S. and member of the Board of Directors of Rheos. “While MALT1 inhibition has held therapeutic promise for some time because of its anti-inflammatory effects, there has been some uncertainty regarding its actual effect on regulatory T cells. These impressive data demonstrate for the first time the potential to achieve efficacy without impacting regulatory T cells. These findings provide compelling evidence in developing therapeutics which 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 multiple primary human cells, disease pathogenesis in a rat model of arthritis and on regulatory T cell (Tregs) function. These findings indicate that a favorable therapeutic window is accessible and may expand beyond what has been observed in non-diseased, naïve animals. The paper includes these key findings:
- MALT1 inhibition attenuated effector functions of multiple primary human cell types that are involved in the pathogenesis of autoimmune and inflammatory diseases, and blocked cytokine expression in stimulated whole blood from multiple species.
- Pharmacologic inhibition of MALT1 reduced disease severity and synovial cytokine production in a preclinical arthritis model.
- Efficacy can be uncoupled from Treg reduction, with lower systemic concentrations of MALT1 inhibitor needed to reduce disease severity compared to that required to reduce Treg numbers.
- Undesirable MALT1 inhibitor-induced Treg reduction was less pronounced in diseased rats than in naïve rats, showing the potential to broaden the therapeutic window for a MALT1 inhibitor drug.
The published data support Rheos Medicines’s development of its lead product candidate, RHX‑317, a novel small molecule MALT1 inhibitor being developed for the treatment of several autoimmune diseases. Because of MALT1’s role in cellular metabolism which differs in heterogeneous patient subsets, the clinical activity of RHX-317 will be monitored by metabolite signatures in clinical studies, opening an opportunity for Rheos to take a precision medicine approach to monitor disease and therapeutic effect in treating autoimmune diseases. RHX-317 has shown efficacy in several validated models of disease, including chronic graft-versus-host disease (cGVHD), rheumatoid arthritis and lupus nephritis.
MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a dual-function scaffolding molecule and paracaspase that is expressed preferentially in immune cells. In addition to its role in NF-κB mediated lymphocyte activation and proliferation, Rheos has shown that MALT1 activity is central to the anabolic shift that fuels pathogenic functions of immune cells. Inhibiting MALT1 attenuates the activity of multiple immune cell types simultaneously to dampen the inflammatory response in the activated immune system. Because of its role in cellular metabolism, the effects of MALT1 inhibition can be monitored by metabolite signatures, opening an opportunity to monitor disease and evaluate activity of therapeutics in patients and patient subsets.
About Rheos Medicines
Rheos Medicines is a biopharmaceutical company developing novel, small molecule medicines to treat autoimmune and inflammatory diseases with greater precision by targeting the metabolic hubs of the immune system. Using our proprietary MetPM™ platform, the Rheos team integrates an unmatched knowledge base of immunometabolism networks based on bioinformatic 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 address autoimmune and inflammatory diseases by targeting fundamental underpinnings of immune system dysfunction while, at the same time, identifying the molecular signatures for patient stratification and selection. Rheos has assembled leading scientists whose discoveries opened the field of immunometabolism, clinicians with a deep understanding of immune-mediated diseases, and an experienced biotech leadership team. 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.
Kathryn Morris, The Yates Network LLC
Hannah Deresiewicz, Stern Investor Relations, Inc.