Bellus Health


P2X3 Inhibition

P2X3 Inhibition

BLU-5937, a highly selective P2X3 antagonist, has the potential to be a differentiated treatment option for chronic cough and chronic pruritus patients.

P2X3, a key sensory receptor in the peripheral nervous system, is responsible for irritation and pain. Its targeting has been validated as a rational approach for treating symptoms of chronic cough in multiple clinical trials. However, it is well-known and widely-documented that a P2X3 antagonist with low selectivity has an adverse effect on taste, likely due to the inhibition of P2X2/3 receptors on the taste buds. On the other hand, a highly selective P2X3 antagonist may not inhibit P2X2/3 receptors, potentially resulting in decreased cough frequency with minimal taste loss. In the Phase 2 RELIEF trial, BELLUS Health’s highly selective P2X3 antagonist (>1500 fold more selective for P2X3 vs P2X2/3) reduced coughing in chronic cough patients with higher baseline cough count, while maintaining taste function.

Based on studied mechanistic similarities between chronic cough and chronic pruritus, BELLUS Health also believes BLU-5937 may be a promising, novel therapeutic for chronic pruritus associated with atopic dermatitis.

In addition to chronic cough and chronic pruritus, BLU-5937 may also have broad applicability across other afferent hypersensitization-related disorders, potentially enabling the Company to build a pipeline of therapies using its P2X3 platform. BELLUS Health is exploring how P2X3 activation can contribute to irritation and pain, and whether inhibition of P2X3 receptors can help treat these afferent hypersensitization-related disorders.

Other Indications Linked to P2X3 Hypersensitization

  • Bladder pain
  • Bronchoconstriction
  • Endometriosis pain
  • Hypersensitive cough
  • Hypertension
  • IBS
  • Migraine
  • Neuropathic pain
  • Sleep apnea