MTX-101 / Mozart Therap - LARVOL DELTA

Mozart Therapeutics Completes Ph1a Study in Healthy Adults; Data Shows MTX-101 is Well Tolerated and Selectively Activates CD8 Treg (PRNewswire) - P1 | N=96 | NCT06324604 | Sponsor: Mozart Therapeutics Australia Pty Ltd | " Mozart Therapeutics, the leading developer of CD8 Treg modulators for the treatment of autoimmune disease, today announce the successful completion of their Phase 1a study of MTX-101 in healthy adults....Data from the study in healthy adults show MTX-101 is well tolerated. Most adverse events were low-grade and there were no serious adverse events. Participants receiving MTX-101 experienced transient and self-limited decreases in lymphocytes, which the Company believes are consistent with the study drug's mechanism of action and indicative of target engagement....Mozart plans to present full data from the Phase 1a study at upcoming medical symposia....The first patients with type 1 diabetes and celiac disease have been enrolled in Part B of the study, which is being conducted at multiple clinical sites in Australia."

P1 data • Trial status • Celiac Disease

MT-101-101: Safety, Pharmacokinetics, and Pharmacodynamics of MTX-101 in Healthy Adults and Patients (clinicaltrials.gov) - P1 | N=96 | Recruiting | Sponsor: Mozart Therapeutics Australia Pty Ltd | Trial completion date: Dec 2025 ➔ Apr 2026 | Trial primary completion date: Dec 2025 ➔ Apr 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Celiac Disease • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Preclinical characterization of MTX-101: a novel bispecific CD8 Treg modulator that restores CD8 Treg functions to suppress pathogenic T cells in autoimmune diseases. (PubMed, Front Immunol) - "MTX-101 reduced antigen induced epithelial cell death in disease affected tissues, including in tissue biopsies from individuals with autoimmune disease (i.e., celiac disease, Crohn's disease). MTX-101 selectively bound CD8 Treg without unwanted immune cell activation or increase of pro-inflammatory serum cytokines and exhibited an antibody-like half-life in pharmacokinetic and exploratory tolerability studies performed using IL-15 transgenic humanized mice with engrafted human lymphocytes, including CD8 Treg at physiologic ratios. Collectively, these data support the development of MTX-101 for the treatment of autoimmune diseases."

Journal • Preclinical • Celiac Disease • Crohn's disease • Gastroenterology • Graft versus Host Disease • Immunology • Inflammation • Inflammatory Bowel Disease • CD4 • CD8 • IL15 • KIR2DL1 • KIR2DL3

Mozart Therapeutics Announces Publication of MTX-101 Preclinical Data Demonstrating Modulation of Regulatory CD8 T Cell Network to Restore Immune Homeostasis (Front Immunol, PRNewswire) - "Mozart Therapeutics...announce today the publication of its first peer-reviewed publication...in the journal Frontiers in Immunology. The publication extends on seminal work (Saligrama et al, 2019; Li et al, 2022) describing a cytolytic CD8 T cell subset (CD8 Treg) with anti-inflammatory effects that is dysfunctional in autoimmune diseases. The work furthers the understanding of the mechanisms underpinning CD8 Treg dysfunctions, as well as preclinical data for the Company's novel bispecific antibody, MTX-101. The data illustrate that MTX-101 selectively binds to human CD8 Treg, restoring their cytolytic functions, resulting in pathogenic CD4 T cell elimination in the periphery and disease-affected tissues ex vivo. Importantly, data demonstrate that the effects of MTX-101 are not broadly immunosuppressive and do not impair responses to viral and bacterial antigens."

Preclinical • Immunology

Mozart Therapeutics Announces Publication of MTX-101 Preclinical Data Demonstrating Modulation of Regulatory CD8 T Cell Network to Restore Immune Homeostasis (Front Immunol, PRNewswire) - "Mozart Therapeutics...announce today the publication of its first peer-reviewed publication...in the journal Frontiers in Immunology. The publication extends on seminal work (Saligrama et al, 2019; Li et al, 2022) describing a cytolytic CD8 T cell subset (CD8 Treg) with anti-inflammatory effects that is dysfunctional in autoimmune diseases. The work furthers the understanding of the mechanisms underpinning CD8 Treg dysfunctions, as well as preclinical data for the Company's novel bispecific antibody, MTX-101. The data illustrate that MTX-101 selectively binds to human CD8 Treg, restoring their cytolytic functions, resulting in pathogenic CD4 T cell elimination in the periphery and disease-affected tissues ex vivo. Importantly, data demonstrate that the effects of MTX-101 are not broadly immunosuppressive and do not impair responses to viral and bacterial antigens."

Preclinical • Immunology

Preclinical Characterization of MTX-101, a Novel KIRxCD8 Targeting Bispecific CD8 Treg Modulator (ADA 2024) - "MTX-101 restores CD8 Treg functions and may provide durable resistance to autoimmune disease progression."

Preclinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD34 • CD8

Mozart Therapeutics Announces Oral Presentation on MTX-101 at the 2024 American Diabetes Association's 84th Scientific Sessions (PRNewswire) - "Mozart Therapeutics...today presented new preclinical data on the Company's lead program, MTX-101. The data were reviewed during an oral presentation at the 2024 American Diabetes Association 84th Scientific Sessions, held June 21–24 in Orlando, FL." "

Preclinical • Metabolic Disorders • Type 2 Diabetes Mellitus

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 2024) - "No strong binding was observed other than expected interactions to its KIR2DL and CD8 targets.In conclusion, nonclinical safety studies support clinical entry into a Ph1a/b healthy adult and patient study. MTX-101 is a promising therapeutic approach to address an underlying cause of autoimmune disease via enhancement of CD8 Treg function."

Clinical • Immunology • Inflammation • CD34 • CD8

Mozart Therapeutics Doses First Cohort of Participants in Phase 1a/b Clinical Trial of MTX-101, in Development for Treatment of Autoimmune Diseases (PRNewswire) - "Mozart Therapeutics...announce the dosing of the first cohort of participants in the Company's initial clinical study of MTX-101, a first-in-class CD8 Treg modulator and autoimmune checkpoint inhibitor....The Phase 1a portion of the study (NCT06324604) is a single and multiple ascending dose escalation study evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MTX-101 in healthy adults. The Phase 1b is a prospective, multi-center, randomized, double-blind, placebo-controlled trial to evaluate safety, PK, PD, and disease-specific biomarkers in patients with type 1 diabetes mellitus or celiac disease."

Trial status • Celiac Disease • Type 1 Diabetes Mellitus

MTX-101, A BISPECIFIC CD8 TREG MODULATOR, CORRECTS THE DYSFUNCTION IN CROHN’S PATIENT CD8 TREG TO RESTORE IMMUNE BALANCE (DDW 2024) - "Treatment with MTX-101 reduced the prevalence of activated CD4 T cells and selectively increased prevalence and Granzyme B content of CD8 Treg but not of single target expressing immune cells e. g. CD8 T cells NK cells. Collectively these data support the development of MTX-101 for the treatment of autoimmune mediated GI disorders and identify markers that could serve as PD markers for MTX-101 in clinical trials."

Clinical • IO biomarker • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Inflammatory Bowel Disease • Oncology • CD4 • CD8 • GZMB • IL15

Safety, Pharmacokinetics, and Pharmacodynamics of MTX-101 in Healthy Adults and Patients (clinicaltrials.gov) - P1 | N=96 | Not yet recruiting | Sponsor: Mozart Therapeutics Australia Pty Ltd

New P1 trial • Celiac Disease • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Mozart Therapeutics Presents Non-clinical Data on Lead Program, MTX-101 for Treatment of Autoimmune Diseases, at Society of Toxicology Annual Meeting 2024 (PRNewswire) - "Presentation highlights include: MTX-101 was well-tolerated following single and multiple doses in the humanized mouse model; MTX-101 showed sustained binding to CD8 Treg and did not demonstrate off-target cell effects or cause an increase in detectable pro-inflammatory serum cytokines; Serum concentrations of MTX-101 indicated high exposure and PK parameters consistent with antibodies; Data derived from the humanized mouse model aligns with previous in vitro and in vivo findings for MTX-101."

Preclinical • Immunology

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 (ACR Convergence 2023) - "Collectively, our data suggest that MTX-101-mediated disruption of the inhibitory autoimmune checkpoint KIR2DL1/2/3 can improve CD8 Treg dysfunctions observed in patients with rheumatologic autoimmune diseases to support durable re-balancing of the immune system."

Preclinical • Ankylosing Spondylitis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Systemic Lupus Erythematosus • CD4 • CD8 • GZMB • IL15 • KIR2DL1

Mozart Therapeutics Presents Preclinical Data for MTX-101, a Novel Bispecific CD8 Treg Modulator for Treatment of Autoimmune Diseases, at American College of Rheumatology Convergence 2023 (PRNewswire) - "Presented findings demonstrate: CD8 Treg are present in rheumatological autoimmune diseases and show decreased expression of functional proteins and reduced responsiveness to stimulation relative to healthy donor CD8 Treg; MTX-101 selectively binds CD8 Treg and enhances their killing of self-reactive CD4 T cells by blocking inhibitory KIR; Enhanced MTX-101 mediated CD8 Treg function prevents self-reactive CD4 T cell expansion and inflammation, without unwanted immune cell activation or increase of pro-inflammatory cytokines."

Preclinical • Immunology

Mozart Therapeutics Presents Preclinical Data for MTX-101, a Novel CD8 Treg Network Modulator for Treatment of Autoimmune Disease, at FOCIS 2023 Annual Meeting (PRNewswire) - "Mozart Therapeutics...announced the presentation of preclinical pharmacologic and tolerability data for MTX-101, a bispecific autoimmune checkpoint inhibitor, at the Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS 2023)....MTX-101 is well-tolerated following a single dose in humanized mice; MTX-101 selectively acts on CD8 Treg in blood and tissues and does not cause activation of other immune cells nor an increase of pro-inflammatory cytokines; MTX-101 possesses a favorable and antibody-like pharmacokinetic profile."

Preclinical • Immunology

Mozart Therapeutics Raises $25 Million in Expanded Series A Financing to Support Clinical Development of First-in-Class CD8 Treg Modulators for the Treatment of Autoimmune Diseases (PRNewswire) - "Mozart Therapeutics...announced it has raised $25 million from new investors in a Series A extension, bringing the total raise to $80 million. The proceeds will be used to advance the company's lead candidate, MTX-101, into first-in-human clinical trials and to support pipeline expansion....The company anticipates filing an IND and initiating a Phase 1 clinical trial for MTX-101 in early 2024."

Financing • IND • New P1 trial • Immunology