camlipixant (GSK5464714) / GSK - LARVOL DELTA

Evaluation of the Effect of Rifampin and Rabeprazole on the Pharmacokinetics of Camlipixant (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Bellus Health Inc. - a GSK company | N=32 ➔ 42

Enrollment change • Cough • Respiratory Diseases

Camlipixant: Data from P3 CALM-1 trial (NCT05599191) for refractory chronic cough in H2 2025 (GSK) - Q3 2024 Results: Data from P3 CALM-2 trial (NCT05600777) for refractory chronic cough in H2 2025

P3 data • Chronic Cough • Cough

A Study of Camlipixant in Male and Female Healthy Participants and Participants With Hepatic Impairment Aged 18-75 Years of Age (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Bellus Health Inc. - a GSK company | Trial primary completion date: Jul 2024 ➔ Oct 2024

Trial primary completion date • Cough • Hepatology • Respiratory Diseases

DESIGN OF THE LANDMARK CALM-1 AND CALM-2 PHASE 3 CLINICAL TRIALS OF CAMLIPIXANT IN REFRACTORY CHRONIC COUGH (CHEST 2024) - P3 | "The CALM-1 and CALM-2 trials will evaluate efficacy, safety, and tolerability of camlipixant in a broad population of patients with RCC (including UCC) utilizing a run-in period and novel stratification by cough frequency. CLINICAL IMPLICATIONS: The novel design features of the CALM-1 and CALM-2 trials offer the potential for improved assessment of benefit/risk in the population of patients with greatest unmet clinical need. Given the absence of any available treatment indicated for RCC in the USA, the CALM-1 and CALM-2 trials will provide evidence of the efficacy and safety of a potentially novel treatment option for patients with RCC (including UCC)."

Clinical • P3 data • Chronic Cough • Cough • Immunology • Respiratory Diseases

Determination of Camlipixant (BLU-5937) P2X3 antagonist activity in a sensory neuronal model and bronchial epithelial cells (ERS 2024) - "Both PNEs and PBECs express functional P2X3 receptors. Camlipixant acted as a potent P2X3 antagonist of receptor excitation in both cell types."

Chronic Cough • Cough • Respiratory Diseases

Prior and concomitant medication use in patients with refractory chronic cough: post-hoc analysis of SOOTHE (ERS 2024) - P2b | " SOOTHE (NCT04678206) was a randomised, multi-centre, double-blind, placebo-controlled, parallel arm, dose-finding study of camlipixant for RCC treatment... Despite CM use for underlying conditions, pts had inadequate control of their cough, largely unrelated to age or gender."

Clinical • Retrospective data • Asthma • Chronic Cough • Cough • Gastroenterology • Gastroesophageal Reflux Disease • Immunology • Respiratory Diseases

A Study to Investigate the Effect of Food on Camlipixant Concentrations in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Bellus Health Inc. - a GSK company | Not yet recruiting ➔ Recruiting

Enrollment open • Cough • Respiratory Diseases

Camlipixant: Data from P3 CALM-1 trial (NCT05599191) for refractory chronic cough in 2025 (GSK) - Q2 2024 Results: Data from P3 CALM-2 trial (NCT05600777) for refractory chronic cough in 2025

P3 data • Chronic Cough

Camlipixant: Acceptance of regulatory submissions in US/EU for refractory chronic cough (based on CALM-1 and CALM-2 trials) in H2 2025 (GSK) - Q2 2024 Results

EMA filing • FDA filing • Chronic Cough

Assessment of the Pharmacokinetics of BLU-5937 Extended Release Prototypes and a BLU-5937 Immediate Release Reference Formulation (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Bellus Health Inc. - a GSK company | Recruiting ➔ Completed | N=32 ➔ 14

Enrollment change • Trial completion • Cough • Respiratory Diseases

A Study to Investigate the Effect of Food on Camlipixant Concentrations in Healthy Participants (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P1 trial • Cough • Respiratory Diseases

A Second Drug Binding Site in P2X3. (PubMed, bioRxiv) - "P2X3 binds to camlipixant at a previously unidentified drug-binding site and functions as an allosteric inhibitor. Structure-activity studies combined with modeling and simulations have shed light on the mechanisms underlying the selective targeting and inhibition of P2X3 by camlipixant, distinguishing it from other members of the P2X receptor family."

Journal • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Camlipixant Reduces Burden of Cough-related Urinary Incontinence in Patients With Refractory Chronic Cough in Post-hoc Analysis of A Phase 2b Trial (ATS 2024) - P2b | "A general, validated UI scale was useful for assessing changes in cough-related UI in patients with RCC; however, use of the ICIQ-SF in the assessment of cough-related UI warrants further study. Treatment of cough with camlipixant may be associated with a reduction in the burden of cough-related UI in patients with RCC."

Clinical • P2b data • Retrospective data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases • Urinary Incontinence • Urology

Benefit-risk profile of P2X3 receptor antagonists for treatment of chronic cough: Dose-response model-based network meta-analysis. (PubMed, Chest) - "When used at safe doses, gefapixant had a favorable risk-benefit profile compared to the other four agents. Camlipixant showed initial promise, which may be further investigated by phase III trials currently underway."

Benefit-risk assessment • Journal • Retrospective data • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

A Study of Camlipixant in Male and Female Healthy Participants and Participants With Hepatic Impairment Aged 18-75 Years of Age (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Bellus Health Inc. - a GSK company | Not yet recruiting ➔ Recruiting | Trial primary completion date: Dec 2024 ➔ Jul 2024

Enrollment open • Trial primary completion date • Cough • Hepatology • Respiratory Diseases

Assessment of the Pharmacokinetics of BLU-5937 Extended Release Prototypes and a BLU-5937 Immediate Release Reference Formulation (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Bellus Health Inc. - a GSK company | Active, not recruiting ➔ Recruiting

Enrollment open • Cough • Respiratory Diseases

Evaluation of the Effect of Rifampin and Rabeprazole on the Pharmacokinetics of Camlipixant (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Bellus Health Inc. - a GSK company | Not yet recruiting ➔ Completed

Trial completion

Evaluation of the Potential Drug-drug Interactions Between Gemfibrozil or Dabigatran Etexilate and Camlipixant (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Bellus Health Inc. - a GSK company | Not yet recruiting ➔ Completed

Trial completion

Camlipixant: Acceptance of regulatory submissions in US/EU for refractory chronic cough (based on CALM-1 and CALM-2 trials) in 2025 (GSK) - Q4 & FY2023 Results

European regulatory • NDA • Chronic Cough

A Study of Camlipixant in Male and Female Healthy Participants and Participants With Hepatic Impairment Aged 18-75 Years of Age (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P1 trial • Cough • Hepatology • Respiratory Diseases

A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough (CALM-2) (clinicaltrials.gov) - P3 | N=825 | Recruiting | Sponsor: Bellus Health Inc. - a GSK company | Trial completion date: Jul 2025 ➔ Jun 2026

Trial completion date • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

CALM-1: A 52-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough (clinicaltrials.gov) - P3 | N=825 | Recruiting | Sponsor: Bellus Health Inc. - a GSK company | Trial completion date: Jul 2025 ➔ Mar 2026 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Chronic Cough • Cough • Pulmonary Disease • Respiratory Diseases

Evaluation of the Pharmacokinetics and Safety of BLU-5937 in Healthy Adult Japanese and Caucasian Subjects (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Bellus Health Inc. - a GSK company

New P1 trial

Assessment of the Pharmacokinetics of BLU-5937 Extended Release Prototypes and a BLU-5937 Immediate Release Reference Formulation (clinicaltrials.gov) - P1 | N=32 | Active, not recruiting | Sponsor: Bellus Health Inc. - a GSK company | Recruiting ➔ Active, not recruiting | N=16 ➔ 32 | Trial completion date: Mar 2023 ➔ May 2024 | Trial primary completion date: Feb 2023 ➔ May 2024

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date

Camlipixant: Data from P3 CALM-1 trial (NCT05599191) for refractory chronic cough in H2 2025 (GSK) - Getting ahead of Respiratory Diseases with GSK management: Data from P3 CALM-2 trial (NCT05600777) for refractory chronic cough in H2 2025

P3 data • Chronic Cough