URJA

Restoring the engine of anti-tumor immunity

Urja Therapeutics develops therapies that restore immune metabolic fitness in cancer, with the goal of helping more patients benefit from immunotherapy.

Our science →

Rotating model: human METRNL, predicted structure from AlphaFold DB (Q641Q3-2)

The problem

Immunotherapy has transformed cancer care. Most patients still don't respond.

Checkpoint inhibitors are now standard of care across many advanced cancers. Among US patients with advanced cancer, more than half are eligible for one, yet only about one in five responds.

Source: Haslam et al., Int J Cancer, 2025

57%Eligible for a checkpoint inhibitor
~20%Respond
Of patients with advanced cancer, 57% are eligible for a checkpoint inhibitor and about 20%, one in five, respond.
The missing layer

Immuno-oncology has built two layers. The third is missing.

Release the brakes

Checkpoint inhibitors release the restraints on immune cells.

Press the accelerator

Cell therapies, bispecifics and other agents push immune cells to attack harder.

Restore the engine

Immune cells need energy to fight. In advanced cancers, that engine is disrupted, and no approved therapy restores it.

Our approach

Target the controls, not the fuel.

Earlier efforts treated immune metabolism as a fuel problem in the tumor environment. Urja targets the signaling pathways that program how immune cells make and spend energy.

How we approach it →
Lead program

URJ-101

A first-in-class antibody against METRNL, a signal that disrupts mitochondrial function in anti-tumor T cells.

View pipeline →
Founders

Immune metabolism is the next frontier in immuno-oncology.

Urja was founded by physician-scientists who have spent their careers developing immunotherapies for cancer and studying why they fail.

Meet the team →

Our science

Why immune cells run out of energy in tumors, and how we restore it.

Effector function costs energy

To find and kill cancer cells, T cells need a sustained supply of energy, produced mainly by their mitochondria. In many advanced cancers, T cells become exhausted and lose the ability to kill tumor cells, and many can no longer make and spend energy properly.

Exhaustion has several drivers. Metabolic failure is a core one, and no approved therapy addresses it.

Baseline immune state predicts response

Immune metabolism is one of the fastest-moving areas of cancer research. Recent clinical studies show that a patient's baseline immune state, including mitochondrial function, helps predict who responds to checkpoint inhibitors. The state of the engine helps determine who benefits.

Why fixing the fuel hasn't worked

Earlier approaches targeted the tumor's metabolic environment, blocking enzymes that deplete nutrients T cells need or that produce immunosuppressive metabolites. Several looked promising in early studies but did not improve outcomes in late-stage randomized trials.

These approaches act indirectly, on an environment shared by tumor and immune cells, where redundant pathways compensate.

Our approach

Target the controls, not the fuel

Urja targets the signaling pathways that program how immune cells make and spend energy. We look for control points with three properties:

One upstream control.
A single node that governs immune metabolism, rather than one of many redundant fuel lines.
A direct effect on the immune cell.
So the effect can be measured in patients' own immune cells.
Validation in human tumors.
Present in the exhausted cells we aim to rescue.
The engine map

Where the controls sit

Inside the T cell, in the signals that reach it, and in the immune cells around it.

In the neighborhood

Myeloid and regulatory cells whose own metabolism suppresses T cells

At the cell boundary

Signals that disrupt T-cell mitochondrial function

METRNL, our lead program

Mitochondrial transfer between tumor and immune cells

Inside the T cell

Mitochondrial quality control: clearing damaged mitochondria

Many cells and pathways, one measure of success: T cells that keep killing tumors.

METRNL, our first control point

METRNL is a cytokine released in tumors by chronically stimulated T cells and myeloid cells. Our scientific founders discovered that METRNL disrupts mitochondrial function in CD8+ T cells, forcing them off their endurance engine (oxidative phosphorylation) and into a short-lived sprint mode (glycolysis). In a tumor already depleted of glucose, that sprint cannot be sustained, and the T cells fail.

In human tumors, METRNL is enriched in exhausted tumor-infiltrating T cells across several cancer types. In preclinical models, removing METRNL restored T-cell respiration, slowed tumor growth and extended survival.

Source: Jackson et al., Immunity, 2024

See our pipeline →

What METRNL does to a T cell's energy

Illustrative schematic, not experimental data
Schematic of T-cell energy supply over time in a tumor. Before METRNL, energy is steady from oxidative phosphorylation. After METRNL, the cell switches to glycolysis: energy spikes briefly, then collapses as glucose runs out. Without METRNL, the steady supply continues. Energy supply Time in the tumor → METRNL arrives Endurance Sprint Without METRNL T cell fails

Endurance engine: oxidative phosphorylation. Mitochondria supply the steady energy T cells need to keep finding and killing cancer cells.

Sprint mode: glycolysis. METRNL disrupts mitochondrial function and forces this short-lived mode, which may briefly increase energy supply. In a tumor already depleted of glucose, the sprint cannot be sustained, and the T cell fails.

Without METRNL. In preclinical models, removing METRNL restored T-cell respiration.

Pipeline

Our lead program targets METRNL. Additional programs address other control points of immune metabolism.

Urja Therapeutics development pipeline
ProgramTargetModalityFocus Stage
URJ-101 METRNL Antibody-based Solid tumors Discovery
Additional programs Undisclosed control points of immune metabolism To be determined Solid tumors Exploratory, in founder labs

A first-in-class anti-METRNL antibody

URJ-101 is designed to block METRNL and restore the metabolic fitness of anti-tumor T cells directly, bypassing the tumor's metabolic environment.

We are evaluating URJ-101 on its own and alongside existing immunotherapies, with the goal of helping more patients respond.

Our antibody candidates have been generated and characterized, and in vivo efficacy studies are next.

Beyond METRNL

METRNL is the first of many control points.

We believe immune metabolism in cancer holds a large, untapped set of therapeutic targets. Working closely with our founding laboratories, we are identifying and evaluating additional programs across the engine map.

Explore the engine map →

Interested in partnering?

Contact us →

Team

Urja was founded by physician-scientists who have spent their careers developing immunotherapies for cancer and studying why they fail. It is run with urgency, rigor, and capital discipline by a new generation of biotech operators.

Founders

Michael Lim

Michael Lim, MD

Co-founder and Chair, Scientific Advisory Board

Chair of Neurosurgery, Stanford Medicine

Chris Jackson

Chris Jackson, MD

Co-founder and Scientific Lead

Associate Professor of Neurosurgery, Johns Hopkins

Daniel Chai

Daniel Chai, MD

Co-founder and Chairman of the Board

Managing Partner, Turret Capital

Leadership

Vedik Navale

Vedik Navale

Chief Executive Officer

Henry Park

Henry Park

Chief Financial Officer

Publications

The science inspiring Urja

Contact

Get in touch

We welcome conversations with partners, investors and scientists who share our interest in immune metabolism.

Partnering and investors
vnavale@urjatherapeutics.com
Careers
We are not currently hiring, but we're always glad to hear from scientists who share our interest in immune metabolism.

Email

vnavale@urjatherapeutics.com

For partnering, investment and general inquiries.

Email us →