CAMBRIDGE, Mass.– Rheos Medicines, a biopharmaceutical company bringing molecular targeting and precision treatment to autoimmune and inflammatory diseases, today announced new preclinical data showing the potential for MALT1 inhibitors for the treatment of autoimmune and inflammatory diseases, as well as the power of metabolic signatures to define patient subpopulations in these heterogeneous diseases. The results demonstrating MALT1 inhibition support Rheos’s lead product candidate, RHX-317, a novel, small molecule MALT1 inhibitor, that the company is initially developing for the treatment of chronic graft versus host disease (GVHD). The data will be presented at ACR Convergence 2021, the annual meeting of the American College of Rheumatology, which will be held virtually from November 3-9, 2021.
“We are delighted to share new data demonstrating MALT1’s therapeutic mechanisms for molecularly targeting immune-mediated diseases, like chronic GVHD, as well as our ability to identify molecular signatures that can inform patient stratification and enable precision medicine-based approaches to treating complex autoimmune and inflammatory diseases,” said Barbara Fox, Ph.D., Chief Executive Officer of Rheos. “Together, the presentations exemplify our strategy to leverage insights from metabolic hubs to transform the treatment of autoimmune and inflammatory disease by delivering new molecularly targeted medicines to patient subsets with specific metabolic signatures, who are most likely to benefit from those drugs. Building on the results presented at ACR, we are excited to advance our MALT1 inhibitor, RHX-317, as a new targeted therapy for the treatment of autoimmune and inflammatory diseases, including an initial indication in chronic GVHD.”
In results presented in a poster titled “Pharmacological Inhibition of MALT1 Reverses Activation-Induced Metabolic Reprogramming and Ameliorates Autoimmune Pathogenesis in Multiple Animal Models of Chronic Inflammation,” Rheos scientists describe new preclinical data elucidating the role of MALT1 in driving the anabolic shift that fuels the pathogenic functions of immune cells, an orchestrated group of metabolic changes referred to by Rheos as the anabolic hub. Rheos has designed its MALT1 inhibitors to target the anabolic hub and inhibit the activity of multiple immune cell types, attenuating the inflammatory response in the activated immune system. Highlights from the poster include these findings:
- Immunoreceptor tyrosine-based activation motif (ITAM)-activation induced an anabolic phenotype across multiple immune cell types.
- Pharmacologic inhibition of MALT1 attenuated the anabolic phenotype and blocked multiple effector functions across multiple cell types.
- Dose-dependent activity of small molecule MALT1 inhibitors were observed in multiple animal models of autoimmune and inflammatory disease, including a mouse model of chronic GVHD.
- A small molecule MALT1 inhibitor reversed the metabolic changes seen in the inflammatory microenvironment, the localized area surrounding pathological inflammation in specific tissues or organs.
“Our precision medicine approach to autoimmune and inflammatory diseases is built on our deep understanding of immunometabolism, encompassing the cellular metabolism across many immune cell types and enabled by our proprietary MetPM™ platform,” said Dania Rabah, Ph.D., Chief Scientific Officer of Rheos. “We are delighted to share with the clinical community our poster at ACR that presents the results of our bioinformatic analysis of published data of systemic lupus erythematosus patients, demonstrating the power of metabolic activity to stratify patient subtypes for a heterogenous autoimmune disease and showing a new path to identify molecular signatures and to treat autoimmune and inflammatory diseases with better precision.”
In a poster titled, “Transcriptional Subsetting of SLE Patient Cohorts Based on Metabolic Pathway Activity,” Rheos scientists demonstrated the pivotal role of metabolic pathway activity in stratifying patients with systemic lupus erythematosus (SLE), a heterogeneous autoimmune disease. In this poster, Rheos scientists demonstrate:
- Metabolic pathway activity can be derived from a transcriptional signature and this metabolic information alone is sufficient to define patient subpopulations in SLE.
- Metabolically-defined subsets are biologically relevant, with the data demonstrating consistency with cell type enrichment tied to known immunopathological features of the disease.
- Patient subsets represent distinct metabolic hubs, the orchestrated metabolic changes that fuel function of immune cells.
