SCIENCE – META

Metabolism at the Core of Autoimmunity

In conditions such as inflammatory bowel disease, multiple sclerosis, and atopic dermatitis, immune cells remain persistently and aberrantly activated. This sustained activation is accompanied by profound metabolic reprogramming — a shift from efficient oxidative phosphorylation to less efficient but rapid glycolysis. The direct consequence of this shift is extensive lactate accumulation.

Chronic Inflammatory Diseases

Autoimmune Diseases

Immune Cell Activation

Metabolic Reprogramming

Lactate Accumulation

Inflammatory Amplification

Current Therapies Focus on Modulating Downstream Inflammatory Cytokines Failing to Regulate Aberrant Immune Cell Activation at the Source

Glucocorticoids

Rapid but non-selective, limited long-term use.

Monoclonal Antibodies

Target specific cytokines; non-response or loss of efficacy.

JAK Inhibitors

Modulate pathways but broad activity raises safety concerns.

Whether broad-spectrum suppression, precise targeting, or signaling blockade, current therapies largely focus on modulating downstream inflammatory cytokines. One core question remains unanswered: Can we recalibrate immune cell function by targeting the metabolic source?

META’s Novel Therapeutic Approach Rewriting the Fundamental Logic of Immune Response at the Source

Original Biological Theory

Novel Target Validation

Oral Small Molecule Inhibitor

Deciphering the Warburg Effect

Dr. Ke Xu has spent over a decade deciphering the molecular mechanism of the Warburg effect. He proposes a pioneering strategy: restore immune function from its origin by precisely modulating immune cell metabolism.

True First-in-Class Innovation

Based on this novel theory, META identified LDHA as a key immunometabolic checkpoint and developed MP-5342, a first-in-class oral LDH inhibitor. Unlike existing therapies targeting cytokines or signaling pathways, our approach modulates immune cells at the metabolic level for broader and more precise control of inflammation.

Research Achievements

These findings link metabolism, immune signaling, inflammation, supporting immunometabolism-targeted therapies and LDH-targeted drug development.

Science, 2016

354(6311): 481-484

Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism

Science, 2021

371(6527): 405–410

Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity

Immunity, 2021

54(5): 976–987

Glycolytic ATP fuels phosphoinositide 3-kinase signaling to support effector T helper 17 cell responses

Gastroenterology, 2026

170(6 Suppl):S1257-S1258

LDHA Is a Promising Metabolic Target in Inflammatory Bowel Disease

Science Advances

2023;9(12):eadd9554

The lactate dehydrogenase (LDH) isoenzyme spectrum enables optimally controlling T cell glycolysis and differentiation

Nature Immunology

2023;24(8):1358-1369

Distinct metabolic requirements regulate B cell activation and germinal center responses

A Novel Autoimmune Therapy

Metabolism at the Core of Autoimmunity

Chronic Inflammatory Diseases

Immune Cell Activation

Lactate Accumulation

Current Therapies Focus on Modulating Downstream Inflammatory Cytokines Failing to Regulate Aberrant Immune Cell Activation at the Source

Glucocorticoids

Monoclonal Antibodies

JAK Inhibitors

META’s Novel Therapeutic Approach Rewriting the Fundamental Logic of Immune Response at the Source

Deciphering the Warburg Effect

True First-in-Class Innovation

Research Achievements

Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism

Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity

Glycolytic ATP fuels phosphoinositide 3-kinase signaling to support effector T helper 17 cell responses

LDHA Is a Promising Metabolic Target in Inflammatory Bowel Disease

The lactate dehydrogenase (LDH) isoenzyme spectrum enables optimally controlling T cell glycolysis and differentiation

Distinct metabolic requirements regulate B cell activation and germinal center responses

LDHA
The Metabolic Gatekeeper

Discovery Begins Asking How Life Works

A Novel Autoimmune Therapy

Metabolism at the Core of Autoimmunity

Chronic Inflammatory Diseases

Immune Cell Activation

Lactate Accumulation

Current Therapies Focus on Modulating Downstream Inflammatory Cytokines Failing to Regulate Aberrant Immune Cell Activation at the Source

Glucocorticoids

Monoclonal Antibodies

JAK Inhibitors

META’s Novel Therapeutic Approach Rewriting the Fundamental Logic of Immune Response at the Source

Deciphering the Warburg Effect

True First-in-Class Innovation

Research Achievements

Aerobic glycolysis promotes T helper 1 cell differentiation through an epigenetic mechanism

Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity

Glycolytic ATP fuels phosphoinositide 3-kinase signaling to support effector T helper 17 cell responses

LDHA Is a Promising Metabolic Target in Inflammatory Bowel Disease

The lactate dehydrogenase (LDH) isoenzyme spectrum enables optimally controlling T cell glycolysis and differentiation

Distinct metabolic requirements regulate B cell activation and germinal center responses

LDHA The Metabolic Gatekeeper

Discovery Begins Asking How Life Works

LDHA
The Metabolic Gatekeeper