– Preclinical data demonstrate MALT1 inhibitors effectively target the anabolic hub to modulate key drivers of autoimmune and inflammatory diseases –

– Bioinformatic data confirm metabolic pathway signatures can stratify patients within a heterogenous autoimmune disease, demonstrating potential for precision medicine-based approach to treating autoimmune and inflammatory diseases –

– Two poster presentations at ACR Convergence 2021 –

CAMBRIDGE, MA, USA I November 01, 2021 I 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.

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 Metabolic Hubs

Metabolic hubs comprise the central orchestrated metabolic events that control immune cell function; in autoimmune and inflammatory diseases these hubs provide an opportunity for therapeutic interventions. These groupings of molecular pathways are essential in multiple immune cell subtypes which regulate metabolism and drive system-wide transition in immunologic function. Within each metabolic hub, there are multiple pathways that can be interrogated to identify drug targets for molecularly targeted medicines and associated molecular signatures for patient stratification and selection.

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.

SOURCE: Rheos Medicines