Rheos Medicines to Present Data at ACR 2021 for MALT1 Inhibitors in Autoimmune and Inflammatory Disease and Announces RHX-317 as First Development Candidate

Rheos Medicines, a biopharmaceutical company bringing molecular targeting and precision treatment to autoimmune and inflammatory diseases, today announced it will present two poster presentations at ACR Convergence 2021, the annual meeting of the American College of Rheumatology which will be held virtually from November 3-9, 2021. Also today, Rheos announced that it has designated RHX?317, a novel small molecule MALT1 inhibitor, as its first development candidate, with plans for initial clinical evaluation for the treatment of chronic graft-versus-host disease (GVHD) and potential future expansion to other autoimmune and inflammatory diseases.

At ACR, Rheos will present a poster 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, including RHX-317, to target the anabolic hub and inhibit the activity of multiple immune cell types, attenuating the inflammatory response in the activated immune system. New preclinical data will be presented demonstrating that Rheos's MALT1 inhibitors modulate key pathogenic drivers of disease and are efficacious in multiple animal models of inflammatory disease.

"The designation of RHX-317 as our first clinical development candidate represents important progress for Rheos, as we look forward to advancing our MALT1 inhibitor as a new targeted therapy for the treatment of autoimmune and inflammatory diseases, including chronic GVHD," said Barbara Fox, Ph.D., Chief Executive Officer of Rheos Medicines. "Our excitement around RHX-317 is further supported by the new preclinical data that will be presented at ACR, which shows that MALT1 inhibitors can successfully target the anabolic hub, one of the key metabolic hubs that modulates the orchestrated action of multiple immune cells that drive autoimmune and inflammatory diseases. By targeting metabolic hubs, we are opening up a more precise, molecularly-targeted approach to treating heterogeneous autoimmune and inflammatory diseases that affect millions of patients."

Also at ACR, Rheos will present a poster showing that transcriptionally defined metabolic pathway signatures can stratify patients within the heterogeneous autoimmune disease, systemic lupus erythematosus (SLE). Leveraging its proprietary MetPM^tm platform, Rheos has gained new insights from bioinformatic integration and comparison of multi-omic analyses to identify molecular signatures and determine patient subsets in this complex disease. Results from the SLE study lay the groundwork for Rheos's efforts to apply a precision medicine approach to its drug development for autoimmune and inflammatory diseases, including GVHD.

The details of Rheos's presentations at the upcoming ACR 2021 meeting are as follows:

"Pharmacological Inhibition of MALT1 Reverses Activation-Induced Metabolic Reprogramming and Ameliorates Autoimmune Pathogenesis in Multiple Animal Models of Chronic Inflammation"

• Poster session: Abstract Number 1509, Session: T Cell Biology & Targets in Autoimmune & Inflammatory Disease
• Date and time: November 9th, 8:30 ? 10:30 EDT
• Authors: Brad Biswas, PhD, Chaitanya A. Kulkarni, PhD, Mya Steadman, Ynes Helou, PhD, Katie Sellers, PhD, Keng Soh, PhD, Aditi Chalishazar, Mehmet Badur, PhD, Joanna DiSpirito, PhD, Brian DeChristopher, PhD, John Monroe, PhD, Dania Rabah, PhD, Barbara Fox, PhD, and Andrew Long, PhD

"Transcriptional Subsetting of SLE (Systemic Lupus Erythematosus) Patient Cohorts Based on Metabolic Pathway Activity"

• Poster session: Abstract Number 0523, Session B, Genetics, Genomics and Proteomics
• Date and time: November 7th, 8:30-10:30 EDT
• Authors: Diogo M. Camacho, PhD, Jennifer L. Swantek, PhD, Keng Soh, PhD, Jurre Kamphorst, PhD, Vivek Kaimal, PhD, John Monroe, PhD, Edward M. Driggers, PhD

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-?B 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 MetPMtm 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.

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