Clinical-stage biopharmaceutical company Verona Pharma updated the market on its operations on Tuesday, confirming that in the quarter to 31 March it successfully completed two further clinical trials with nebulized RPL554 ahead of schedule.
The AIM-traded firm also reported positive top-line data from a Phase 2b clinical trial for maintenance treatment of chronic obstructive pulmonary disease (COPD) during the period:
It explained that its product candidate, RPL554, was a first-in-class inhaled dual inhibitor of the enzymes phosphodiesterase 3 and 4, or PDE3 and PDE4, that acted as both a bronchodilator and an anti-inflammatory agent in a single compound.
Verona Pharma said it was developing RPL554 for the treatment of COPD and cystic fibrosis (CF), and potentially for asthma.
RPL554 was said to have met the company's primary endpoint at all doses, showing a "statistically significant difference" when compared to placebo, with absolute changes from baseline >200mL in peak FEV1 after four weeks of dosing.
No minimum effective dose could be determined, the company said.
The peak bronchodilator effect was observed at the first dose, and was sustained over four weeks.
Statistically significant improvements in average FEV1 over 12 hours were observed at all doses after the first administration, and that effect was sustained over four weeks.
Verona said the study did not demonstrate "consistent improvements" in trough FEV1.
Recording of daily COPD symptoms, using E-RS, demonstrated a significant, clinically relevant, progressive improvement in total COPD symptoms, including improvements in breathlessness, chest symptoms, and cough and sputum.
There was a strong trend of improvement in quality of life score, with the board reporting that the St. George's Respiratory Questionnaire (SGRQ-C) of >2.5 units was observed in all dose groups after four weeks.
Patients' Global Impression of Change indicated that patients felt better on RPL554 compared to placebo, with the company also finding that RPL554 was well tolerated at all doses with an adverse event profile similar to placebo.
During the quarter, Verona also reported positive top-line data from a Phase 2a clinical trial to study the pharmacokinetic and pharmacodynamic profile in cystic fibrosis, with the pharmacokinetic profile said to have been consistent with that observed in patients with COPD, although with lower peak serum levels of RPL554 in CF patients.
The serum half-life was dose-dependent; 7.5 to 10.1 hours for 1.5 mg and 6 mg, respectively.
RPL554 also elicited a "statistically significant" increase in average FEV1 in treated patients for 1.5 mg and 6 mg at 4, 6 and 8 hour time points.
Verona said the drug was well-tolerated in the patient group, with an adverse event profile consistent with other studies with RPL554.
Preparations for a Phase 2 nebulized RPL554 add-on study to LABA/LAMA or triple therapy were continuing to progress according to plan, with the clinical trial expected to start in the third quarter of 2018.
MDI and DPI formulation work was also progressing "well" with pre-clinical studies with RPL554 in new formulations now expected to complete in the second half of 2018.
On the financial front, Verona reported net cash, cash equivalents and short term investments at 31 March of £72.6m, down from £80.3m at the end of December.
For the three months ended 31 March, the company reported an operating loss of £5.9m, widening from £4.1m a year ago, and reported a loss after tax of £15.2m, more than the £1.9m it reported at the same time in 2017.
Operating expenses increased due to an expansion of research and development activity, the board said.
The increase in the net loss was said to reflect the finance expense for the increase in the fair value of the liability representing the warrants over Verona shares, of £9.0m, which is a non-cash item.
Reported losses per share totalled 14.5p for the three months ended 31 March, up from 3.7p year-on-year.
Net cash used in operating activities for the three months was £6.2m, rising from £3.5m last year and reflecting increased clinical activities.
"We are pleased to have reported positive top-line data from two clinical studies that we completed ahead of schedule during the first quarter," said Verona CEO Jan-Anders Karlsson.
"In our largest and longest trial to date, a 403 patient four-week Phase 2b trial, RPL554 demonstrated a significant and clinically meaningful improvement in lung function in COPD patients, as well as a clinically meaningful improvement in daily reported COPD symptom scores in all sub-domains, that continued to improve over the four-week treatment period."
Karlsson said the data gave the board confidence in progressing nebulised RPL554 towards Phase 3 studies in COPD patients.
"Likewise, the positive data in our Phase 2a trial in CF patients now makes a proof-of-concept study in patients with CF feasible.
"We are delighted with the significant progress we made with RPL554 during the reporting period, providing further support for RPL554 potentially becoming an important novel and well-differentiated treatment for patients with COPD, as well as CF."