Rheos Medicines Presents New Data Supporting MALT1 Inhibition as Novel Strategy for Precision Medicine-Based Approach to Treating Chronic Graft-Versus-Host Disease

December 13, 2021 |

4 min read

Rheos Medicines, today announced new preclinical data supporting MALT1 inhibition as a novel approach for the treatment of chronic Graft-Versus-Host Disease (cGVHD) and the use of differential metabolic pathway analysis to subset patients in this heterogeneous population.

– Preclinical data demonstrate MALT1 inhibition targets pathogenic activity of the activated immune system, showing efficacy in a model of cGVHD –

– Metabolomic analysis reveals an induction of the anabolic hub in cGVHD, which is normalized with inhibition of MALT1 –

–Metabolic pathway analysis classifies heterogeneous GVHD patient population based on differential cellular metabolism –

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Rheos Medicines, a biopharmaceutical company bringing molecular targeting and precision treatment to autoimmune and inflammatory diseases, today announced new preclinical data supporting MALT1 inhibition as a novel approach for the treatment of chronic Graft-Versus-Host Disease (cGVHD) and the use of differential metabolic pathway analysis to subset patients in this heterogeneous population. Rheos’s lead product candidate, RHX-317, is a novel, small molecule MALT1 inhibitor initially in development for the treatment of chronic GVHD. The data will be presented at the 63rd Annual Meeting of the American Society of Hematology (ASH), being held in Atlanta and virtually, December 11-14, 2021.

“We are excited to share the growing body of data demonstrating the utility of MALT1 inhibition and metabolic pathway signatures for the precision treatment of cGVHD,” said Barbara Fox, Ph.D., Chief Executive Officer of Rheos. “This composite dataset reveals the many ways in which our understanding of cellular metabolism could transform the treatment of patients with autoimmune and inflammatory diseases, such as cGVHD. By applying a metabolic lens, we are able to glean insights at many levels – from defining metabolic hubs that drive system-wide changes in immunologic function, to identifying pathway clusters to establish distinct patient subsets, to pinpointing specific targets and biomarkers to achieve therapeutic results – which may enable us to deliver the first precision medicines for these challenging, heterogenous diseases.”

In data presented in a poster titled, “Allosteric Inhibition of MALT1 is Efficacious in a Model of Chronic Graft-Versus-Host Disease (cGVHD) and Modulates Immunometabolic Activation,” Rheos scientists describe studies establishing the role of cellular metabolism in cGVHD, informing the identification of MALT1 inhibition as a novel strategy to attenuate inflammatory response in the activated immune system of cGHVD patients and the subsetting of patients based on differential metabolic pathway regulation. Highlights from the poster include these findings:

MALT1 inhibition attenuates effector functions of multiple human cell types that are known to be involved in cGVHD pathogenesis.
Pharmacologic inhibition of MALT1 is efficacious in a murine model of sclerodermatous cGVHD (scGVHD) and ameliorates T-cell-mediated inflammation in the skin.
The induction of anabolic pathways in scGVHD correlates with disease severity and can be normalized by MALT1 inhibition.
Transcript-based metabolic analysis reveals four patient subpopulations within cGVHD, each characterized by a distinct metabolic pathway signature, suggesting novel heterogeneity that can be used to identify different disease subsets and potentially inform precision medicine-based approaches to treatment.

About MALT1
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.