Addex Therapeutics has reached a key clinical milestone in schizophrenia drug development. Its spin-out company, Neurosterix, has initiated a Phase 1 clinical trial of NTX-253, a next-generation oral therapy targeting the muscarinic M4 receptor.
What Is NTX-253?
NTX-253 is a potent, selective, orally available positive allosteric modulator (PAM) of the muscarinic M4 receptor. Unlike traditional antipsychotics, it does not directly block dopamine receptors.
Instead, it:
- Fine-tunes muscarinic signalling
- Indirectly modulates dopamine pathways
- Aims to reduce psychosis with fewer side effects
This represents a novel mechanism in schizophrenia treatment.
Phase 1 Study: What’s Being Evaluated
The Phase 1 study is being conducted in healthy volunteers.
Its primary objectives include:
- Safety and tolerability
- Pharmacokinetics (how the drug behaves in the body)
- Pharmacodynamics (biological effects of the drug)
This is NTX-253’s first-in-human clinical evaluation.
Why Target the M4 Muscarinic Receptor?
The M4 receptor is a validated target in schizophrenia research.
Current antipsychotics:
- Primarily block dopamine receptors
- Often cause metabolic, cognitive, and motor side effects
M4 PAMs offer a different path.
Research suggests they can:
- Reduce psychotic symptoms
- Avoid movement disorders
- Minimise metabolic complications
All without peripheral muscarinic side effects seen with direct agonists.
Preclinical Data Supports Clinical Advancement
NTX-253 showed strong promise in preclinical studies.
Key findings included:
- Robust antipsychotic-like activity
- Favourable safety profile
- Reversal of dopamine-driven behaviours in animal models
These results supported progression into human trials.
Strategic Importance for Addex and Neurosterix
Neurosterix was spun out of Addex in April 2024.
Key background details:
- Raised $65 million in Series A financing
- Funding led by affiliates of Perceptive Advisors
- Addex retains a 20% equity stake
According to Addex CEO Tim Dyer, NTX-253 represents a differentiated therapeutic approach with potential safety and efficacy advantages.
How This Fits Into Addex’s Broader Pipeline?
Addex continues to focus on allosteric modulators for neurological disorders.
Its lead program:
- Dipraglurant, an mGlu5 negative allosteric modulator
- Being evaluated for brain injury recovery
- Including post-stroke and traumatic brain injury
The Neurosterix spin-out allows sharper focus on schizophrenia.
The Bigger Picture
Schizophrenia treatment has seen limited mechanistic innovation for decades. NTX-253 signals:
- A move beyond dopamine-centric drugs
- Growing interest in muscarinic modulation
- Renewed momentum in CNS drug innovation
If successful, M4 PAMs could reshape the antipsychotic landscape.
Bottom Line
Neurosterix’s Phase 1 start is more than a routine trial update.
It reflects:
- Confidence in M4-based schizophrenia therapies
- Smart portfolio separation by Addex
- A serious attempt to improve safety and outcomes in psychiatric care
NTX-253 is now officially in the clinic—and worth watching closely.
