Science
Mozart is developing CD8 Treg modulators for the treatment of autoimmune diseases.
CD8 Treg Orchestrate a Healthy Immune Surveillance System
Regulatory CD8 T cells (CD8 Treg) are essential for the regulation and maintenance of immune homeostasis. They are responsible for controlling pathogenic immune responses that are directed at self (auto) antigens. CD8 Treg act upstream in the immune surveillance system, recognizing and cytolytically eliminating these pathogenic CD4 T cells, thereby preventing their expansion and maintaining immune self-tolerance.
CD8 Treg Dysfunction Leads to Immune Imbalance
In autoimmune disease, CD8 Treg fail to control the expansion of pathogenic CD4 (pCD4) T cells. Proliferation of pCD4 T cells initiates a cascade of downstream events, including the production of proinflammatory cytokines and self-reactive antibodies in peripheral blood and tissue. This, in turn, can lead to reduced self-tolerance, tissue damage, and other hallmarks of autoimmune disease.
CD8 Treg dysfunction is due in part to the expression of inhibitory killer immunoglobulin-like receptors (KIR) that suppress the activation of CD8 Treg via competitive binding to Major Histocompatibility Complex Class I (MHC I). In this context, inhibitory KIR acts as an autoimmune checkpoint, playing a role in regulating immune tolerance.
OUR APPROACH: CD8 Treg Modulators
Current therapies are designed to treat the symptoms of autoimmune disease, or to target pathogenic cells or proinflammatory mediators that emerge downstream in the inflammatory cascade. These approaches often leave patients at increased risk for broad immune suppression.
Mozart is targeting a fundamental cause of immune dysregulation, developing therapeutics that selectively target the regulatory CD8 T cell network and counteract early events in the inflammatory cascade of autoimmune disease. Therapeutic modulation of this network is designed to restore the intrinsic function of CD8 Treg to suppress and eliminate pathogenic immune cells, preventing downstream inflammation and tissue destruction and providing durable control of autoimmune disease.
Posters and Publications
Preclinical Characterization of MTX-101: A Novel Bispecific CD8 Treg Modulator that Restores CD8 Treg Functions to Suppress Pathogenic T Cells in Autoimmune Diseases | Frontiers in Immunology (doi: 10.3389/fimmu.2024.1452537), November 2024
Characterization of a Reversibly Dysfunctional Regulatory CD8 T Cell Population Responsible for Pathogenic T Cell Elimination in T1D Patients | 20th Immunology of Diabetes Society Congress (IDS 2024), November 2024
Nonclinical Toxicology and Safety Studies of MTX-101, an Inhibitory KIR2DL x CD8 Targeting Bispecific CD8 Treg Modulator, Enabling Clinical Development as Therapeutic for the Treatment of Autoimmune Disease | FOCIS Annual Meeting, June 2024 #W114
MTX-101, a Bispecific CD8 Treg Modulator, Corrects the Dysfunction in Crohn’s Patient CD8 Treg to Restore Immune Balance | 2024 DDW (Digestive Disease Week®), May 2024 #Su1736
Pre-clinical Pharmacology and Tolerability Characterization of a Novel KIR x ICOS Targeting Bispecific CD8 Treg Modulator | AAI Immunology, May 2024 #4471
Nonclinical Assessment of Toxicity and Pharmacology of MTX-101, a Novel KIRxCD8 Targeting Bispecific CD8 Treg Modulator, in Humanized Mouse | Society of Toxicology Meeting, March 2024 #5081
Pre-Clinical Characterization of MTX-101, a Novel Bispecific CD8 Treg Modulator with the Potential to Restore CD8 Treg Functions in Patients with Rheumatological Autoimmune Diseases | American College of Rheumatology (ACR), November 2023
Pre-clinical Pharmacologic and Tolerability Characterization of MTX-101, a Novel KIR x CD8 Targeting Bispecific CD8 Treg Modulator | FOCIS 2023 Annual Meeting, June 2023 #1517124
Pre-clinical Pharmacologic and Tolerability Characterization of a Novel KIR x CD8 Targeting Bispecific CD8 Treg Modulator | American Association of Immunologists (AAI) Annual Meeting, May 2023 #2638
A KIR x CD8 Targeting Bispecific Modulator Enhances Regulatory CD8 T Cell Functions, and Reduces Inflammation in Models of Autoimmune Disease | American Association of Immunologists (AAI) Annual Meeting, May 2023 #2804
A Novel Bispecific CD8 Treg Modulator Targeting Cytolytic CD8 Regulatory T cells Reduces Pathogenic CD4 T cells and Inflammation in Translational Models of Intestinal Autoimmune and Inflammatory Disease | 2023 Crohn’s and Colitis Congress, January 2023 #124
A Newly Discovered Regulatory CD8 T Cell Network Has The Potential To Regulate And Eliminate Pathogenic CD4 T Cells In Autoimmune Mediated Disease Of The Gut​ | 2022 Digestive Disease Week® (DDW) Conference, May 2022, Presentation # sa1117
Bispecific CD8 Treg modulators regulate a novel regulatory CD8 T cell network and eliminate pathogenic CD4 T cells in live cell co-culture system | American Association of Immunologists (AAI) Annual Meeting, May 2022, Abstract # 1090
Demonstration of regulatory CD8 T cell prevalence, phenotype, and functions in autoimmune patients treated with a tolerizing peptide vaccine | American Association of Immunologists (AAI) Annual Meeting, May 2022, Abstract # 889