23 May 2019 - - Canadian biopharmaceutical company Bellus Health Inc. (TSX: BLU) has presented results from the clinical Phase 1 study of BLU-5937, an orally-administered P2X3 antagonist, being developed for the treatment of refractory chronic cough, the company said.

Clinical data presented at the American Thoracic Society International Conference in Dallas, Texas showed that BLU-5937 is well-tolerated and importantly, provide the first clinical evidence that a highly selective P2X3 antagonist is associated with little to no impact on taste.

Data presented, in the form of a poster presentation entitled "BLU-5937 a Highly Selective P2X3 Homotrimeric Receptor Antagonist with Improved Taste Safety Profile in Healthy Subjects," may be accessed on the Events and Presentations page under the Investors and News section of the company's website.

The Phase 1 study was a randomized, double-blind, placebo-controlled study of 90 healthy adult subjects. Participants were divided into 6 single ascending dose (SAD; n=60) and 3 multiple ascending dose (MAD; n=30) cohorts.

The primary objectives were to assess the safety, tolerability (including taste perception), and pharmacokinetic profile. BLU-5937 was found to be safe and well-tolerated at all doses, with very low incidence of transient and sporadic taste adverse events.

Based on human pharmacokinetic profile seen in the Phase 1 study and achieving dose levels required to reach optimal efficacy in the preclinical cough models, the anticipated therapeutic doses of BLU-5937 are expected to be 50mg - 100mg BID.

At the anticipated therapeutic doses of 50mg 100mg BID, BLU-5937 did not cause any loss of taste perception and only one subject out of 24 reported transient taste alteration. No subject reported total loss of taste at any dose.

There were no cases of taste alteration or taste loss at 200mg BID.

Incidence of taste alteration was higher at supra-therapeutic doses (≥ 400mg) and analysis of drug blood levels suggests it may correlate with drug exposure that partially inhibits P2X2/3 receptors.

In the MAD cohorts, five subjects (4 at 400mg BID; 1 at 100mg BID) experienced taste alteration events: all 5 subjects reported a taste event on the first dose; 3 of them experienced a second episode during the 7-day dosing period and 2 had no further event.

There were no serious adverse events reported, and no subjects withdrew prematurely due to an adverse event. Overall incidence of AEs was comparable between placebo and BLU-5937. The other most frequent AEs were: taste alteration (19.4%), headache (11.1%), numbness (11.1%), nausea, dizziness and heartburn.

No significant trends of mean changes in vital signs, electrocardiogram, and clinical laboratory values were observed.

Results from the Phase 1 study support the advancement to a Phase 2 study, which is expected to be initiated in mid-2019, with top-line results anticipated in mid-2020.

This will be a dose-escalation, crossover design study to assess the efficacy, safety, and tolerability of BLU-5937 at four doses: 25, 50, 100, and 200mg BID. In the Phase 1 study, 2.5% of subjects tested at these doses had a taste alteration event.

Approximately fifty patients with refractory unexplained chronic cough are expected to be enrolled at 12 clinical sites in the United Kingdom and United States.

BLU-5937, a highly selective P2X3 antagonist - (>1500 fold) for human P2X3 receptors versus P2X2/3 receptors - has the potential to be a best-in-class therapeutic for refractory chronic cough patients.

The P2X3 receptor in the cough reflex pathway is a rational target for treating refractory chronic cough, and it has been validated in multiple clinical studies.

With a modestly-selective P2X3 antagonist therapy for chronic cough, an adverse effect on taste perception is a well-known and widely-documented tolerability issue.

The company believes that a highly selective P2X3 antagonist can reduce coughing in patients with refractory chronic cough, while maintaining taste function, by not inhibiting P2X2/3 receptors.

In addition to chronic cough, BLU-5937 may potentially have clinical benefit in other afferent hypersensitisation-related disorders, such as visceral pain, hypertension, and migraine, among others. Bellus Health is exploring how P2X3 activation can contribute to irritation and pain, and how inhibition of P2X3 receptors may be able to help treat these afferent hypersensitization-related disorders.

Bellus Health is a clinical-stage biopharmaceutical company developing novel therapeutics for the treatment of chronic cough and other hypersensitization-related disorders. The company's lead product candidate, BLU-5937, is being developed for the treatment of chronic cough.

Chronic cough is a cough lasting more than eight weeks and is associated with significant adverse physical, social and psychosocial effects on health and quality of life.

It is estimated that approximately 26m adults in the United States suffer from chronic cough with more than 2.6m having unexplained or refractory chronic cough lasting for more than a year.

There are limited treatment options for refractory chronic cough and no currently approved therapeutics.