The science

Depleting the cell at the center of the disease.

Calixis is developing an oral small molecule that inhibit wild-type KIT — the receptor mast cells depend on to survive. Here is how the approach works, what we are studying, and where we are headed.

Mechanism of action

The KIT survival signal — and how we switch it off

Mast cells rely on a receptor called KIT. When its natural partner, stem cell factor (SCF), binds KIT, the receptor sends a signal that keeps the mast cell alive. Block that signal, and mast cells can no longer survive.

In disease — signal ON Extracellular SCF ligand KIT receptor (dimerized) Intracellular Active signaling (P) Survival & proliferation Mast cell persists With Calixis KIT inhibitor — signal OFF SCF ligand Kinase blocked No survival signal Mast cell depleted
Left: stem cell factor (SCF) binds KIT, driving the receptor to pair up and signal for mast-cell survival. Right: THB335 blocks KIT's kinase activity, removing the survival signal so the mast-cell population declines. Illustration is schematic.
1

Bind

Our small molecule enters the mast cell and occupies KIT's kinase site, where the receptor normally relays its signal.

2

Block

With the kinase silenced, SCF can no longer tell the mast cell to survive and multiply — even when SCF is present.

3

Deplete

Deprived of their survival signal, mast cells decline in number, reducing the source of the mediators that drive disease.

Why "wild-type" matters

A different target than cancer KIT inhibitors

You may have heard of KIT inhibitors in oncology. Those are built to hit mutated KIT that drives certain tumors.

Calixis focuses on wild-type KIT — the normal, unmutated receptor found on healthy mast cells. Our goal is to modulate normal mast-cell biology in allergic and inflammatory disease, a fundamentally different objective, with selectivity designed for that setting.

  • Wild-type selective
  • Oral small molecule
  • Designed for chronic use
  • Non-oncology
Wild-type KIT Calixis focus Mutated KIT Oncology target
Calixis targets the normal (wild-type) receptor on healthy mast cells — distinct from the mutated KIT addressed by cancer therapies.
Mast cells & chronic spontaneous urticaria

From a single cell to a chronic disease

Chronic spontaneous urticaria (CSU) is defined by recurring hives and swelling that appear without an obvious trigger for six weeks or more. Mast cells are central to this process.

1 · Mast cells accumulate

Mast cells reside in the skin, maintained by KIT signaling, ready to respond to stimuli.

2 · They degranulate

The cells release histamine and other mediators into surrounding skin tissue.

3 · Symptoms appear

Mediators cause the wheals, swelling, and intense itch that define the disease — often for years.

Because mast cells are upstream of the many mediators involved, reducing the cells themselves is a strategy to address the disease closer to its source.

Pipeline

Where our programs stand

Our lead program is in Phase 2 in chronic spontaneous urticaria, with additional mast-cell–driven indications planned.

ProgramTargetIndicationStageStatus
THB335
Oral · lead candidate
Wild-type KIT Chronic spontaneous urticaria
DiscoveryINDPh 1Ph 2Ph 3
Phase 2 · ongoing
THB335
Oral · lifecycle
Wild-type KIT Additional mast-cell driven diseases
DiscoveryINDPh 1Ph 2Ph 3
Planning
THB3093
Oral · pipeline
Wild-type KIT Mast-cell–driven diseases
DiscoveryINDPh 1Ph 2Ph 3
Lead Nominated
The platform

Built to reach many diseases

Chronic spontaneous urticaria is a clear, mast-cell–driven starting point. But the same biology recurs across allergy, dermatology, and beyond. Our long-term vision is a portfolio of therapies that share one core idea — that carefully depleting mast cells can relieve disease at its source. Each new indication is chosen where the evidence for mast-cell involvement is strong.

  • Chronic urticaria
  • Allergic disease
  • Mast cell disorders
  • Atopic conditions
  • Respiratory
Chronicurticaria Allergicdisease Mast celldisorders Asthma Atopicskin GI More KIT inhibition

Want to go deeper on the science?

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Contact our team

Calixis's investigational compounds have not been approved by the U.S. Food and Drug Administration or any other regulatory authority. Their safety and efficacy have not been established. Diagrams on this page are schematic and simplified for general audiences. This website is not medical advice.